Children Dental Procedures

Planning and Care
for Children and

Adolescents with Dental
Enamel Defects
Etiology, Research
and Contemporary
Management
Bernadette K. Drummond
Nicola Kilpatrick Editors
123
Planning and Care for Children and
Adolescents with Dental Enamel Defects
Bernadette K. Drummond
Nicola Kilpatrick
Editors
Planning and Care for

Children and Adolescents
with Dental Enamel
Defects
Etiology, Research and Contemporary
Management
Editors
Bernadette K. Drummond, BDS, MS, PhD Nicola Kilpatrick, BDS, PhD
Oral Sciences Cleft and Craniofacial Research
University of Otago School of Dentistry Murdoch Childrens Research Institute
Dunedin Melbourne Victoria
New Zealand Australia
ISBN 978-3-662-44799-4 ISBN 978-3-662-44800-7 (eBook)

DOI 10.1007/978-3-662-44800-7
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This book is dedicated to our PhD
supervisors, John Murray, John McCabe and
Martin Curzon with advice from Colin
Robinson and John Weatherell who inspired
us both to constantly question, reflect and
explore our clinical experiences. Together
with our many colleagues, they have encour-
aged us to strive for excellence in both the
management of and outcomes for children,
adolescents and their families.
Preface
The prevalence of developmental defects of enamel (DDE) is reportedly increasing

worldwide. It is difficult to assess this accurately, as in the past the greater preva-
lence of dental caries may have had a significant impact on the diagnosis of DDE by
masking its presence. Clinically, defects vary greatly in their appearance in terms of
size, color, and shape. DDE may affect both primary and permanent dentitions and
can be either generalized across one or both dentitions or localized to specific teeth.
The structure of enamel in affected teeth differs, such that there may be a quantita-
tive reduction in enamel (known as hypoplasia) or a qualitative defect (known as
hypomineralization), though often defects comprise a combination of the two.
Despite the growing burden associated with treating affected individuals, there
remains a lack of understanding of the etiology of DDE and evidence of clinical
outcomes to support management.
When clinicians are faced with a child who has hypomineralized and/or hypo-
plastic teeth, it can be difficult to plan care for many reasons. Often, the child is
young and has had little or no experience of dentistry. Apart from the difficulties for
the child, this creates stress for the parents and puts pressure on clinicians trying to
decide on the best way to manage the young patient. Affected teeth are difficult to
anesthetize, and treatment can be uncomfortable. It is also clear that individuals
with teeth affected by DDE experience significantly more restorative procedures
throughout childhood and adolescence and have higher levels of dental anxiety.
Poor esthetics coupled with increased sensitivity may further exacerbate the child’s
anxiety and have a real impact on their quality of life. Parents report that children
eat slowly or refuse some foods, although they often do not complain directly of
pain. Children note that they cannot eat ice cream or that people, including teachers
and peers, comment on their chalky or discolored anterior teeth.
The protein content in hypomineralized enamel is significantly higher than in
otherwise healthy enamel, which in turn alters its structure and interferes with the
adhesion of conventional resin-based dental restorative materials. When a clinician
looks at affected teeth for the first time, they should be aware that the child is likely
to require a lifetime of care, even if the teeth remain caries free. This can be an
overwhelming prospect when considering the best approach to early management
so as to prepare the individual for the longer-term definitive solutions, which often
cannot be finally decided until the child is in late adolescence or early adulthood.
When severe defects are localized to one or only a few posterior teeth, it may be
vii
viii Preface
appropriate to extract these compromised teeth. However, it is important to consider

the impact of such extractions on the developing occlusion in order to optimize
definitive occlusal outcomes. Finally, there are financial considerations to be taken
into account both immediately and in the long term, which also will impact on the
management choices that families will be able to make.
With all this in mind, the aims of this book are to summarize the current under-
standing of DDE in the primary and permanent dentitions, to discuss its impact on
children and adolescents, and to provide guidance on treatment planning and manage-
ment. The prevalence and etiology of DDE are addressed in Chaps. 1, 2, and 3.
Chapters 4 and 5 review the contemporary understanding of the genetic influences on
DDE and the potential associations of DDE with systemic conditions and syndromes.
Dental professionals can play an important role in the diagnosis of systemic condi-
tions if they record patterns of defects and take careful histories of other related health
signs and symptoms. Chapter 6 is devoted to presenting information on the structure
and composition of defective enamel. This is to encourage clinicians to think about
how affected teeth behave in the oral environment and consider the impact of this on
restorative materials and treatment techniques. Affected teeth pose particular chal-
lenges in relation to resin bonding, and clinicians have to consider where to place
restoration margins and whether/how to pretreat the enamel to improve adhesion.
Chapter 7 summarizes the current knowledge of the impact of DDE from the
patient’s perspective. There is emerging awareness of the impact of DDE on chil-
dren’s and adolescents’ quality of life not only in terms of the psychosocial influ-
ences of altered appearance but also as a result of a young person’s experience of
complex and often repeated dental interventions. This chapter highlights the impor-
tance of giving careful consideration to planning not only the obvious clinical treat-
ment needs but also the longer-term treatment needs in the context of the broader
psychosocial demands and individual/family expectations.
In planning a definitive outcome, clinicians have to consider the implications of
growth on the developing occlusion, particularly where teeth have a very poor prog-
nosis and extractions are being considered. Chapter 8 reviews dental and occlusal
development. While specialist orthodontic input is ideal, this chapter also acknowl-
edges that this is not always possible and gives an overview of the aspects of occlu-
sion that should be considered when making decisions surrounding the choice and
timing of extractions. The first chapter looking at the management of DDE (Chap. 9)
is devoted to managing sensitivity, improving enamel mineralization, and prevent-
ing dental caries and erosion in affected teeth. Two Chaps. (10 and 11) address the
immediate and intermediate restorative management of primary and permanent
teeth with DDE. This includes the management of permanent teeth through adoles-
cence, while planning the permanent restoration options. All these chapters give
options and recommendations that are supported, where available, with contempo-
rary evidence. The final chapter (Chap. 12) offers an interesting glimpse into
cutting-edge research, in which techniques to regenerate enamel and develop
enamel–like restorative materials offer hope for the future. As access to research
reporting becomes increasingly available to all clinicians, this chapter is a guide on
what to continue to search for in the future.
Preface ix
This book is intended to provide contemporary information on both DDE and its
impact during childhood. Each of the chapters covering specific aspects of DDE has
been written to stand alone. However, where appropriate, the reader is directed to
further linked information in other chapters. Although guidance is offered on vari-
ous management options from both preventive and restorative perspectives, it is not
intended to suggest that these are the only options. Clinicians are encouraged to use
the information to consider the best pathway for each individual patient after taking
account of the child’s and family’s perspectives, the developing occlusion, the clini-
cian’s own skills, and the severity of the presenting anomaly.
Dunedin, New Zealand Bernadette Kathleen Drummond, BDS, MS, PhD

Melbourne, Australia Nicky Kilpatrick, BDS, PhD
Acknowledgements
Professor J. Kirkham for her insights into Chap. 13.

Dr. Supriya Raj for her amazing work organizing the references throughout the book.
xi
Contents
1 Dental Enamel Defects in the Primary Dentition:

Prevalence and Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
W. Kim Seow
2 Enamel Defects in the Permanent Dentition:
Prevalence and Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Robert P. Anthonappa and Nigel M. King
3 Molar Incisor Hypomineralization and Hypomineralized
Second Primary Molars: Diagnosis, Prevalence, and Etiology . . . . . . 31
Karin L. Weerheijm, Marlies E.C. Elfrink, and Nicky Kilpatrick
4 Syndromes and Diseases Associated with
Developmental Defects of Enamel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Mike Harrison, Angus Cameron, and Nicky Kilpatrick
5 Amelogenesis Imperfecta: Current Understanding
of Genotype-Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
John Timothy Wright
6 Molar Incisor Hypomineralization: Structure,
Composition, and Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Erin K. Mahoney and Rami Farah
7 The Psychosocial Impacts of Developmental Enamel
Defects in Children and Young People . . . . . . . . . . . . . . . . . . . . . . . . . 85
Zoe Marshman and Helen D. Rodd
8 Examination and Treatment Planning for Hypomineralized
and/or Hypoplastic Teeth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Bernadette K. Drummond and Winifred Harding
9 Managing the Prevention of Dental Caries
and Sensitivity in Teeth with Enamel Defects. . . . . . . . . . . . . . . . . . . 113
Felicity Crombie and David J. Manton
xiii
xiv Contents
10 Restorative Management of Dental Enamel Defects

in the Primary Dentition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Monty Duggal and Hani Nazzal
11 Restorative Management of Permanent Teeth Enamel
Defects in Children and Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Suzanne M. Hanlin, Lucy A.L. Burbridge,
and Bernadette K. Drummond
12 Future Possibilities for Managing Dental Enamel Defects:
Recent and Current Research Approaches . . . . . . . . . . . . . . . . . . . . 157
Agata Czajka-Jakubowska, Jun Liu, Sywe-Ren Chang,
and Brian H. Clarkson
13 Final Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Bernadette K. Drummond and Nicky Kilpatrick
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Contributors
Robert P. Anthonappa, BDS, MDS, PhD Department of Paediatric Dentistry,

School of Dentistry, Faculty of Medicine, Dentistry and Health Sciences,
University of Western Australia, Perth, WA, Australia
Lucy A.L. Burbridge, BDS, DipConSed, MClinDent Paediatric Dental
Department, Newcastle Dental Hospital, Newcastle Upon Tyne, UK
Angus Cameron, BDS, MDSc Department of Pediatric Dentistry, Westmead
Hospital and The University of Sydney, Westmead, NSW, Australia
Sywe-Ren Chang, MS Department of Cariology, Restorative Sciences and
Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
Brian H. Clarkson, BChD, MS, PhD Department Of Cariology,
Restorative Sciences and Endodontics, School of Dentistry,
University of Michigan, Ann Arbor, MI, USA
Felicity Crombie, BDSc (Hons), PhD Growth and Development Unit,
Melbourne Dental School, University of Melbourne, Melbourne, VIC, Australia
Agata Czajka-Jakubowska, PhD Department of Maxillofacial Orthopedics
and Orthodontics, Poznan University of Medical Sciences, Poznan, Poland
Bernadette K. Drummond, BDS, MS, PhD Department of Oral Sciences,
Faculty of Dentistry, University of Otago, Dunedin, New Zealand
Monty Duggal, BDS, MDSc, PhD Department of Paediatric Dentistry,
School of Dentistry, University of Leeds, Leeds, West Yorkshire, UK
Marlies E.C. Elfrink, PhD Paediatric dentist Mondzorgcentrum Nijverdal and
member Paediatric REsearch Project (PREP), Department of Cariology
Endodontology Pedodontology, Academic Centre for Dentistry (ACTA),
Amsterdam, The Netherlands
Rami Farah, BDS, MPhil, DClinDent, PhD Department of Oral Sciences,
Faculty of Dentistry, University of Otago, Dunedin, New Zealand
Suzanne M. Hanlin, BDS, MDS, GradDipHealInf Department of Oral
Rehabilitation, University of Otago, Dunedin, New Zealand
xv
xvi Contributors
Winifred Harding, BDS, MDS Department of Oral Sciences,

Discipline of Orthodontics, Faculty of Dentistry,
University of Otago, Dunedin, New Zealand
Mike Harrison, BDS, MScD, MPhil Department of Pediatric Dentistry,
Guy’s and St Thomas’ Dental Institute, London, UK
Nicky Kilpatrick, BDS, PhD Cleft and Craniofacial Research,
Murdoch Childrens Research Institute, Melbourne, VIC, Australia
Nigel M. King, BDS Hons, MSc Hons, PhD Department of Paediatric Dentistry,
School of Dentistry, Faculty of Medicine, Dentistry and Health Sciences,
University of Western Australia, Perth, WA, Australia
Jun Liu, PhD Department of Cariology, Restorative Sciences and Endodontics,
School of Dentistry, University of Michigan, Ann Arbor, MI, USA
Erin K. Mahoney, BDS, MDSc PhD Department of Dentistry,
Hutt Valley District Health Board, Wellington, New Zealand
David John Manton, BDSc, MDSc, PhD Growth and Development Unit,
Melbourne Dental School, University of Melbourne, VIC, Australia
Zoe Marshman, BDS, MPH, DDPH, PhD Academic Unit of Dental Public
Health, School of Clinical Dentistry, University of Sheffield, Claremont Crescent,
Sheffield, South Yorkshire, UK
Hani Nazzal, BDS, PhD Department of Paediatric Dentistry, School of Dentistry,
University of Leeds, Leeds, West Yorkshire, UK
Helen D. Rodd, BDS (Hons), PhD Department of Oral Health
and Development, School of Clinical Dentistry, University of Sheffield, Sheffield,
South Yorkshire, UK
W. Kim Seow, BDS, MDSc, PhD, DDSc Centre for Paediatric Dentistry,
School of Dentistry, University of Queensland, Brisbane,
QLD, Australia
Karin L. Weerheijm, PhD Paediatric Dentist KINDERTAND Zuid and member
Paediatric REsearch Project (PREP), Department of Cariology Endodontology
Pedodontology, Academic Centre for Dentistry (ACTA), Amsterdam,
The Netherlands
John Timothy Wright, DDS, MS Department of Pediatric Dentistry,
University of North Carolina, School of Dentistry, Chapel Hill, NC, USA
Dental Enamel Defects in the Primary
Dentition: Prevalence and Etiology 1
W. Kim Seow
Abstract
The enamel of the primary dentition undergoes development from approximately
the 13th week of gestation to around 3 years of age when the second primary
molars erupt into the oral cavity. During this period, the developing primary
dentition can be affected by many systemic and local environment insults that
lead to changes in the quality and quantity of the enamel. The systemic influ-
ences that can cause abnormalities in the primary enamel range from pregnancy
conditions such as pre-eclampsia to neonatal disruptions such as preterm births
and postnatal infections such as rubella and chickenpox. The prevalence of
enamel defects has been reported to range from approximately 30 % in the gen-
eral population in USA, Britain, and Australia to over 70 % in preterm children
and indigenous populations worldwide. The high prevalence of enamel hypopla-
sia reflects the vulnerability of developing teeth to environmental changes and
suggests that complications of enamel defects, such as increased caries suscepti-
bility, are common in the primary dentition.
The formation of enamel extends over a considerable period of time in the life of an
individual. In the primary dentition, enamel formation commences at the tips of the
incisors at approximately 15–19 weeks in utero and ends with the emergence of the
second primary molars between 25 and 33 months of age [1]. During this long
period of enamel development, many conditions can adversely affect the enamel-
forming cells causing abnormalities to be produced. As enamel does not remodel,
any aberrations occurring during formation may be permanently recorded on the
surface as visible defects. Such developmental defects of enamel have major clini-
cal significance. Some defects in the anterior teeth can affect aesthetics, cause
severe tooth sensitivity, and impair masticatory function [2]. Importantly, enamel
W.K. Seow, BDS, MDSc, PhD, DDSc

Centre for Paediatric Dentistry, School of Dentistry, University of Queensland,
200 Turbot Street, Brisbane, QLD 4000, Australia
e-mail: [email protected]
© Springer-Verlag Berlin Heidelberg 2015 1

B.K. Drummond, N. Kilpatrick (eds.), Planning and Care for Children
and Adolescents with Dental Enamel Defects: Etiology, Research
and Contemporary Management, DOI 10.1007/978-3-662-44800-7_1
2 W.K. Seow
defects in the primary dentition are now increasingly recognized as a major risk fac-
tor for early childhood caries (ECC) [3].
Presentations of Developmental Defects of Enamel (DDE)
The formation of enamel or amelogenesis begins during the late bell stage of tooth
development when specialized enamel-forming cells, the ameloblasts, are differen-
tiated from the inner enamel epithelium [4]. The initial stages of enamel formation
are characterized by the secretion of specific proteins by the ameloblasts such as
amelogenin and ameloblastin to form an enamel matrix which is later mineralized
[5, 6]. After the laying down of the enamel matrix, the ameloblasts regulate the
removal of water and proteins from the enamel matrix and promote the ingress of
minerals [7]. The cellular and biochemical events that occur during amelogenesis
are complex and can be adversely affected by genetic changes as well as by sys-
temic and local environmental conditions.
Abnormalities that originate during the formation of enamel are commonly
referred to as developmental defects of enamel (DDE) [8]. The presentation and
severity of DDE are dependent on the stage of enamel development at the time of
the insult, as well as the extent and duration of the adverse condition [9]. Quantitative
deficiencies of DDE, which usually arise from disruptions of matrix formation, are
known as enamel hypoplasia and may be expressed as pits, grooves, and thin or
missing enamel [8]. In contrast, qualitative enamel deficiencies are usually associ-
ated with altered enamel mineralization and may be expressed as changes in the
translucency or opacity of the enamel that may be diffuse or demarcated, and col-
ored white, yellow, or brown [8]. Generally, it is thought that the more immature the
stage of enamel formation, the more vulnerable to damage. Disturbances which
occur during the secretory stages of enamel formation are generally thought to
reduce the quantity of enamel formed, and this is usually expressed as enamel hypo-
plasia. In contrast, disturbances at the final stages are usually associated with altered
mineralization of the enamel which manifests clinically as opacities. As the various
primary teeth in a child’s mouth may be at different stages of enamel formation at
the time of an adverse condition, a spectrum of DDE, ranging from mild opacities
to severe enamel hypoplasia, can result from a single insult.
As DDE are permanent records of enamel changes, the location of a defect on the
enamel surface can suggest the timing of the events that disrupted enamel forma-
tion. Although exact timing is often difficult to identify, knowledge of the chronol-
ogy of development of the primary tooth crowns may be useful in estimating the
approximate times of the insults (Table 1.1). Table 1.1 shows that the primary teeth
usually commence mineralization in utero, starting with primary central incisors at
approximately 15–19 weeks, canines at 16–22 weeks, first molars at 19–22 weeks,
and second molars at 20–22 weeks [1]. At birth, the amount of enamel formed is
approximately three-quarters, two-thirds, and one-third of the primary central inci-
sor, lateral incisor, and canine crowns respectively. In addition, at birth, the first
molar cusps are usually formed, but not coalesced, and the second molar cusp tips
are commencing initial mineralization. Table 1.1 also shows that crown formation is
1 Dental Enamel Defects in the Primary Dentition: Prevalence and Etiology 3
Table 1.1 Chronology of tooth crown formation of the primary dentition

Tooth formation Amount of crown formed at
Primary tooth commences birth Crown completed
Incisors 15–19 weeks in utero Central incisors: three-quarters 1.5–3 months
Lateral incisors: two-thirds
First molar 16–22 weeks in utero Cusps formed, not coalesced 5.5–6 months
Canine 19–22 weeks in utero One-third of cusp 9–10 months
Second molar 20–22 weeks in utero Tips of cusps 10–11 months
Reprinted from Sunderland et al. [1]. With permission from Elsevier
complete in the primary incisors by 3 months, the first molars by 6 months, the
canines by 10 months, and the second primary molars by 12 months. After complete
crown formation, the newly formed enamel undergoes a process of maturation and
hardening that continues post-eruption [4].
The enamel formed prenatally may be demarcated from that formed postnatally
by an area of altered enamel known as the neonatal line. This band of abnormal
enamel has a disorganized prism alignment and contains more organic material
compared to the adjacent enamel [10]. As the entire primary dentition commences
calcification before birth, the neonatal line is usually present in all primary teeth
[11]. It may widen to a clinically visible area of abnormal enamel if a child experi-
ences adverse neonatal conditions such as fetal distress and difficult birth delivery.
Many DDE associated with perinatal illnesses are thus located at the neonatal line.
Prevalence
Several indices have been utilized to record DDE, the most popular being a descrip-
tive index, the Developmental Defects of Enamel (DDE) index which does not
attempt to identify the etiology [8]. There have been several modifications of this
index, including simplified versions that can be applied for screening purposes.
Many authors use the simplified modifications of the index to record DDE in the
primary dentition for practical reasons [8]. Variations in prevalence of DDE reported
in different populations are likely to be the result of differing criteria being used to
define enamel defects. In addition, there are population variations resulting from
differences in general health, and background fluoride exposure levels may also
contribute to differences in the reported prevalence of DDE. Furthermore, in many
studies, the recording of DDE in primary teeth several years post-eruption may be
complicated by difficulties in diagnosing DDE once the lesions have become cari-
ous or have been restored [12]. Finally, differing field conditions during examina-
tion for DDE, such as variations in lighting and whether the teeth are dried prior to
recording of the defects, may also contribute to differences in reported prevalence.
As there are few high-quality studies, the true prevalence of DDE in the primary
dentition is unclear. Most prevalence studies on the primary dentition have been
based on convenient samples from the general or special population groups such as
medically compromised children. Table 1.2 lists selected reports of prevalence of
DDE in the primary dentition published since 1996. There are significant variations
4 W.K. Seow
Table 1.2 Prevalence of DDE in the primary dentition by country

Authors Year Country Prevalence
Li et al. [13] 1995 China 22 %
Slayton et al. [14] 2001 USA 33 %
Montero et al. [15] 2003 USA 49 %
Lunardelli and Peres [16] 2005 Brazil 24 %
Chaves et al. [17] 2007 Brazil 44 %
Elfink et al. [18] 2008 Holland 5 % (primary 2nd molars only)
Hong et al. [19] 2009 USA 4 % (primary molars only)
Casanova-Rosado et al. [20] 2011 Mexico 10 %
Seow et al. [21] 2011 Australia 25 %
Correa-Faria et al. [22] 2013 Brazil 30 %
Masumo et al. [23] 2013 Tanzania 33 %
Ghanim et al. [24] 2013 Iraq 7 % (primary 2nd molars only)
in prevalence rates among different countries and population groups. A Chinese

study showed that primary teeth with defective enamel were seen in 24 % of chil-
dren, with opacities contributing 2 % and enamel hypoplasia 22 % [13]. In the USA,
the study of Slayton and co-workers [14] reported a total prevalence of DDE in the
primary dentition of 33 %, with 6 % of healthy children having at least one tooth
with enamel hypoplasia and 27 % having enamel opacities [14]. In another USA
study, Montero and co-workers reported an overall prevalence of DDE in the pri-
mary dentition of 49 % [15], while in Mexico, a DDE prevalence of only 10 % was
found [20]. In Australia, the prevalence of DDE was reported to be 25 % in a pri-
mary school cohort [21], compared with a rate of approximately 24–44 % in Brazil
[16, 17, 22]. In Holland, the prevalence of hypomineralized second primary molars
was reported at 5 % and 4 % at the child and tooth level, respectively, with the
majority of DDE being demarcated opacities [18]. More recently, a study in Iraq
reported that 7 % of children had hypomineralization defects in at least one second
primary molar [24]. In Tanzania, the prevalence of enamel defects was 33 %, with
diffuse opacities constituting the most common defects (23 %), followed by hypo-
plasia (8 %) and demarcated opacities (5 %). In that study, the most frequently
affected teeth were the primary central incisors (approximately 30 %), whereas
lower central incisors (4–5 %) were least frequently affected [23]. Many indigenous
communities, for example, in Australia, Canada, and the USA are reported to have
higher rates of DDE, probably due to increased risks for poorer general health com-
pared to other communities [25].
Distribution
In a study of over 3,200 primary teeth, 5 % of primary teeth had some form of DDE,
and the most prevalent defects were found, in descending order, in the mandibular
second molar, maxillary second molar, mandibular canine, mandibular first molar,
maxillary first molar, maxillary lateral and central incisors, and maxillary canine
[21]. Only a very small percentage of the mandibular central and lateral incisors
exhibited DDE, and these were mainly enamel opacities [21]. In addition, the most
common type of DDE found in the primary dentition was the demarcated opacity,
followed, in turn, by diffuse opacity and enamel hypoplasia. In another study, the
maxillary primary central and lateral incisors were affected by enamel hypoplasia at
the highest frequencies (41 % and 39 %), followed by the maxillary canines (26 %),
maxillary first molars (22 %), and mandibular first molars (19 %) [13].
Etiology
Table 1.3 shows the plethora of conditions that have been associated with DDE in
primary teeth. Hereditary conditions such as amelogenesis imperfecta are caused
by abnormalities in genes involved in enamel formation [26]. Other forms of DDE
that may be inherited include those that are inherited as familial disorders or dys-
morphic syndromes that show enamel defects [27]. Acquired systemic conditions
that can cause DDE may be encountered perinatally, neonatally, or postnatally
and include conditions such as birth trauma, metabolic conditions, and infections.
Adverse conditions experienced by the mother during pregnancy that may cause
DDE in the child include severe maternal vitamin D deficiency [28] and infection
with syphilis [29]. Local factors impacting on the oral cavity, such as trauma and
radiation, can also cause many DDE in the primary dentition. However, evidence
Table 1.3 Etiology of Generalized defects

developmental dental defects I. Inherited
in the primary dentition Amelogenesis imperfecta
Generalized inherited disorder or syndrome with enamel
defect
II. Acquired systemic condition perinatally, neonatally, or
postnatally
Maternal conditions during pregnancy, e.g.,
cytomegalovirus infection, vitamin D deficiency
Birth trauma
Preterm birth
Isolated cleft lip and palate
Nutritional deficiencies
Renal and liver conditions, e.g., renal failure, biliary atresia
Celiac disease
Endocrine, e.g., hypocalcemia, hypoglycemia
Infections from bacteria, viruses and fungi
Chemicals and toxins
Other systemic conditions
Localized factors
I. Trauma, e.g., laryngoscopy
II. Radiation, e.g., cancer treatment
III. Local infection
6 W.K. Seow
for the associations between many of the acquired systemic conditions and DDE
are based mainly on clinical studies and case reports. There are only a few instances
such as the use of tetracyclines where direct causal links have been demonstrated
between an individual adverse condition and enamel changes in primary teeth [30].
Systemic Factors
Hereditary Conditions
Amelogenesis Imperfecta
Amelogenesis imperfecta is a genetic condition in which both dentitions are charac-
terized by enamel defects and will be discussed in detail in Chap. 5.
Generalized Inherited Disorder or Syndrome with DDE

There are several hereditary syndromes that affect the development of enamel in the
primary and permanent dentitions (see Chap. 4). In inherited dermatological syn-
dromes involving the skin, hair, and nails e.g. ectodermal dysplasia, epidermolysis
bullosa, and tuberous sclerosis, both primary and permanent dentitions usually
show generalized DDE [2]. In addition, hereditary conditions associated with
defects in mineralization pathways that involve the parathyroid glands and vitamin
D metabolism often show abnormalities of enamel development. The hypoparathy-
roidism featured in the velocardiofacial syndrome is thought to be associated with
DDE in the primary dentition. The links between hypoparathyroidism and enamel
defects are also encountered in rare congenital conditions such as the autoimmune
polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome [31]. In the inher-
ited types of rickets, e.g., vitamin D-resistant rickets, generalized enamel hypopla-
sia often results from chronic hypocalcemia/hypophosphatemia present in this
condition [32].
Acquired Systemic Conditions
Numerous acquired conditions have been associated with DDE in the primary denti-
tion. Such conditions may be systemic or local and may be timed to the antenatal,
perinatal, or postnatal periods of development. Prenatal factors that have been asso-
ciated with DDE in the primary dentition include failure to access antenatal care,
increased maternal weight gain during pregnancy, pre-eclampsia and maternal
smoking [33]. Maternal vitamin D deficiency during pregnancy that is associated
with hyperparathyroidism has also been associated with enamel defects [28].
Birth Trauma and Adverse Perinatal Conditions

During the time of birth, adverse factors that have been reported to cause DDE
include birth trauma, hypoglycemia, hypocalcemia and neonatal tetany. Many chil-
dren with cerebral palsy caused by fetal distress and children with toxic levels of
Fig. 1.1 The maxillary

primary left central incisor
from a premature born child
shows severe enamel
hypoplasia that is most likely
caused by traumatic
intubation
bilirubin (hyperbilirubinemia) associated with systemic conditions such congenital

bile duct and liver disease have DDE in the primary dentition. In these children it is
thought that the damage sustained by the ameloblasts reflects the systemic distur-
bances caused by these conditions [34, 35].
Premature Birth
The DDE found in prematurely born children may be associated with neonatal com-
plications of birth prematurity such as respiratory, cardiovascular, gastrointestinal
and renal abnormalities, intracranial hemorrhage, hyperbilirubinemia and/or ane-
mia. Deficient gastrointestinal absorption and inadequate supplies of calcium and
phosphorus have also been associated with DDE in the primary teeth of prematurely
born children [36]. Children who are born premature with low birth weight have
been reported to show a higher prevalence of DDE compared to children born full
term with normal birth weight. In children with birth weights less than 1,500 g and
between 1,500 and 2,500 g, the prevalences were found to be 62 and 27 %, respec-
tively, compared with only 13 % in children with normal birth weight [37]. In addi-
tion, in utero insults associated with small-for-gestational status have been recently
suggested as an important cause of enamel hypomineralization/hypoplasia in pri-
mary teeth of very low birth weight children [38].
Local trauma may occur from laryngoscopy and endotracheal intubation which
are often required in prematurely born children during management of respiratory
distress. This can disrupt development of teeth [39]. In a preterm child, due to the
lack of fulcrum support from an extremely small mandible, the laryngoscope is
often placed on the anterior maxillary alveolus during intubation. This may result
in inadvertent pressure being exerted on the developing primary maxillary incisor
teeth. In severe cases, crown distortions, dilacerations and enamel hypoplasia/
hypomineralization can result from such trauma from the laryngoscope. As the
pressure from the laryngoscope is usually exerted on the left side, the most com-
mon teeth affected from laryngoscope trauma are the maxillary left incisor teeth.
Figure 1.1 shows a maxillary primary left central incisor with severe enamel hypo-
plasia in a prematurely born child caused by traumatic intubation during the neo-
natal period.
8 W.K. Seow
Isolated Cleft Lip and Palate

Children with isolated cleft lip and palate have a higher DDE prevalence compared
to normal children, most likely due to the local tissue disruption caused by the cleft-
ing anomaly on enamel formation. DDE in the primary maxillary central incisors
has been reported in 43 % of children with unilateral cleft lip, with the defects
occurring mainly on the cleft side [40]. In another study of 4-year-old children with
cleft lip and palate, 56 % had enamel defects which were mostly opacities [41].
Malnutrition and Nutritional Deficiencies

Postnatal factors occurring in children under the age of 12 months that may cause
DDE in the primary dentition include malnutrition [42] and nutritional deficiencies
particularly intake deficiency and gut malabsorption of vitamins A, C and D; cal-
cium; and phosphorous [43]. In addition, extended breastfeeding without solid sup-
plementation can cause suboptimal nutrition that may be associated with DDE in
young children [33].
Liver and Renal Conditions

As the liver and kidneys are involved in the activation of vitamin D and the calcifica-
tion of bone and teeth, children with liver and renal diseases may be at increased
risk of DDE. In one study over 19 % of children with chronic kidney failure were
shown to have DDE in the primary teeth compared to only 3 % of otherwise unaf-
fected controls [44]. In congenital liver diseases, high levels of circulating bilirubin
cause disruption of ameloblast function which can lead to formation of defects in
the developing enamel (Fig. 1.2) [45].
Celiac Disease and Gastrointestinal Malabsorption

Children with celiac disease may have malabsorption and mineral deficiencies
associated with gut enteropathy. Celiac disease is caused by inflammation of the
bowel resulting from gliadins (gluten proteins) found in wheat and barley trigger-
ing the formation of antibodies which react with the small-bowel tissue. Atrophy
of the intestinal villus results from the inflammation, and absorption of nutrients
such as vitamin D, calcium and phosphorus from the small bowel is affected [46].
As a result of the malabsorption, children with celiac disease are at high risk for
DDE [47, 48]. Scanning electron microscopic studies have shown that the enamel
of children with celiac disease is less mineralized and more irregular compared to
normal teeth [49]. All permanent teeth in children with celiac disease are at risk
however in the primary dentition; the molars are more likely to be affected as they
undergo a significant part of their mineralization after the introduction of gluten
into the diet [50].
Infections
Serious systemic infections during pregnancy and in infancy have been shown to be
associated with DDE in the primary dentition. Potential mechanisms include the
infective microorganisms damaging the ameloblasts directly or altering their cellu-
lar function indirectly through their metabolic products. High temperatures in young
Fig. 1.2 (a) The restored

primary dentition of a child
with a history of hyperbiliru-
binemia from birth. (b) Note
the attempt to improve the
aesthetics of the upper
incisors by placement of
labial composite resin
veneers (Courtesy of
Professor B Drummond)
children associated with urinary tract infections, otitis media and respiratory tract
diseases may also affect ameloblast function resulting in defects of enamel [51].
Bacterial infections including congenital syphilis and meningococcal disease have
also been shown to cause DDE in the primary dentition [52]. Viral infections, in
either the mother during pregnancy or the infant postnatally such as chickenpox,
rubella, measles, mumps and cytomegalovirus are also well known to be associated
with DDE [29]. Figure 1.3 shows a mandibular primary second molar with enamel
hypoplasia that is associated with a previous severe viral infection that occurred at
approximately 12 months of age.
Chemicals and Toxins

Ameloblasts are also highly sensitive to many chemicals and drugs, and DDE have
been reported to result from exposure to agents such as fluoride and some antibiot-
ics or cytotoxic drugs such as those used in chemotherapy. High doses of fluoride
have been shown to cause hypoplasia and enamel opacities in animal models [53].
However prolonged, inadvertent or deliberate ingestion of fluoride toothpaste by
2- to 3-year-olds can only cause hypomineralization of developing permanent
enamel as mineralization of the primary teeth is already completed by this age [54].
Ingestion of fluoride by the mother during pregnancy is not linked to DDE as little
fluoride crosses the placental barrier. Mild diffuse opacities in the primary dentition
have been reported following exposure to high levels of fluoride in water [55]. One
10 W.K. Seow
Fig. 1.3 A mandibular

primary second molar
showing enamel hypoplasia
that is associated with a
severe viral infection at
approximately 12 months of
age
study has suggested that children ingesting fluoride supplements from 6 to 9 months
of age have an increased risk for fluorosis in the primary second molars [56].
High levels of lead from environmental exposures, accidental or pica ingestion
have been shown to cause DDE in the primary dentition [57]. Tetracyclines are also
well known to cause dental discolorations and enamel hypoplasia [30]. Although
most previous reports of tetracycline staining are of permanent teeth, any primary
teeth developing during the time of tetracycline intake could also theoretically be
affected.
Other Systemic Conditions

Multiple birth children are at increased risk for DDE. In a controlled twin study, 21
and 22 % of monozygotic and dizygotic twins had DDE, compared to only 15 % in
singleton children [58]. To date, minimal genetic influence has been found for DDE
from twin studies and the higher prevalence of DDE in twins is likely to be associ-
ated with the greater rate of neonatal complications such as premature births expe-
rienced by multiple birth children.
Although many clinical conditions have been identified as suggested causes of
DDE, it is also possible that the defects result from undiagnosed or subclinical con-
ditions where there is damage to the ameloblasts without obvious clinical symptoms
in the children. For example, in a study of babies who died of sudden infant death
syndrome (a condition of unknown causes), there was good correlation between
identified enamel defects in the primary teeth and the antemortem history and the
autopsy findings [59].
Local Factors Causing DDE
Local insults such as trauma involve only the teeth in the immediate area of damage
in contrast to systemic factors which usually affect all developing teeth. For exam-
ple, local trauma exerted through the thin buccal cortical bone is thought to be the
cause of demarcated opacities commonly observed on the labial surfaces of primary
canines [60]. The reason for the primary canines being at highest risk for DDE is the
fact that the cortical buccal bone overlying the canines is thin, and the developing
tooth buds situated beneath the cortical bone are easily traumatized by external
pressure from accidents, falls or blows etc. Developing teeth exposed to radiation
for treatment of tumors or leukemia are also known to be at risk for a range of devel-
opmental defects including DDE [61].
In conclusion, the high prevalence of enamel defects that is reported in the pri-
mary dentitions of some children reflects the vulnerability of these developing teeth
to environmental changes during gestation and in the immediate postnatal period.
Given the reported complications associated with DDE, such as increased caries
susceptibility, it is important that these defects are identified in young children as
early as possible so that appropriately targeted prevention can be established.
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Enamel Defects in the Permanent
Dentition: Prevalence and Etiology 2
Robert P. Anthonappa and Nigel M. King
Abstract
The prevalence of developmental defects of enamel (DDE) in the permanent
dentition in developed countries has been reported to be in the range of 9–68 %
and with no gender predilection. Several etiological factors have been implicated
as being responsible for DDE in the permanent teeth. Although local, systemic,
genetic or environmental factors have been attributed to DDE frequently they are
likely to be multifactorial in nature. These factors are discussed in relation to the
timing of enamel development with consideration of the evidence, or lack
thereof, for the association between the putative etiological factors and the nature
of the subsequent abnormalities.
Introduction
The first permanent tooth to begin calcification is the first molar. This occurs around
the time of birth, while the anterior teeth commence calcification between 4 and
6 months of age in a sequential order from the central incisor to the canine. The max-
illary lateral incisor is the exception as calcification of this tooth occurs around
10–12 months of age [1]. At around 6 years of age, the first permanent molar tooth
begins to erupt into the oral cavity and by the age of 14 years, most children have all
of their permanent teeth erupted except for their third molars (Table 2.1). Many fac-
tors have been implicated in the etiology of developmental defects of enamel (DDE)
in permanent teeth. This chapter discusses these factors in relation to the timing of
R.P. Anthonappa, BDS, MDS, PhD • N.M. King, BDS Hons MSc Hons, PhD (*)
Department of Paediatric Dentistry, School of Dentistry, Faculty of Medicine,
Dentistry and Health Sciences, University of Western Australia,
17 Monash Avenue, Nedlands, Perth, WA 6009, Australia
e-mail: [email protected];
[email protected], [email protected]

16 R.P. Anthonappa and N.M. King
Table 2.1 The calcification and eruption dates of permanent teeth
Permanent Calcification Crown formation Eruptiona

tooth type begins at completes at Maxillary Mandibular
Central incisor 3–4 mo 4–5 y 7–8 y 6–7 y
Lateral incisor Maxilla: 10–12 mo 4–5 y 8–9 y 7–8 y
Mandible: 3–4 mo 4–5 y
Canine 4–5 mo 6–7 y 11–12 y 9–11 y
First premolar 18–24 mo 5–6 y 10–11 y 10–12 y
Second premolar 24–30 mo 6–7 y 10–12 y 11–13 y
First molar Birth 30–36 mo 5.5–7 y 5.5–7 y
Second molar 30–36 mo 7–8 y 12–14 y 12–14 y
Third molar Maxilla: 7–9 y >16 y >16 y
Mandible: 8–10 y
mo months, y year
a
It is noteworthy that the sequence is not simply in rank order
enamel development and considers the evidence, or lack thereof, for the association
between the etiological factors and the nature of the subsequent abnormalities.
Prevalence of DDE in the Permanent Dentition
Mouth and tooth prevalence are the most commonly used systems to report the
prevalence data for DDE. Mouth prevalence is determined by the inclusion of any
individual who has been found to have at least one tooth affected by the condition,
while tooth prevalence illustrates the percentage of teeth affected per person. Mouth
prevalence figures reflect the extent of the distribution of enamel defects in a popu-
lation group because individuals who are mildly and severely affected are grouped
together. Tooth prevalence indicates the proportion of teeth affected and hence
reflects the severity of the condition [2].
Table 2.2 summarizes the prevalence of DDE in the permanent dentition as
reported in the literature. Wide variations exist in the literature because of the use of
various terminologies and the different diagnostic criteria employed to describe the
enamel defects in the permanent dentition [21, 22, 24, 26]. Nevertheless, the major-
ity of reports have failed to demonstrate any difference in the prevalence of enamel
defects between girls and boys [12, 27]. Furthermore, for all types of enamel defects,
the published mouth prevalence in the permanent dentition ranges from 9.8 % to
93 % [8, 26], while tooth prevalence figures range from 2.2 % to 21.6 % [26, 28].
Etiology of DDE in the Permanent Dentition
Enamel morphogenesis is a continuous, complex process that starts with the secre-
tion of enamel matrix proteins followed by mineralization and finally maturation.
This process has been shown to start at the cusps on the molars and the incisal part
2 Enamel Defects in the Permanent Dentition: Prevalence and Etiology 17
Table 2.2 The prevalence figures, reported in the literature, for any type developmental defects
of enamel in the permanent dentition of healthy children
F level Age Prevalence %

Author Year Country (ppm) (years) Mouth Tooth
Suckling et al. [3] 1985 New Zealand 1.0 12 56.6 18.8
Dooland and Wylie [4] 1989 Australia 1.0 8–9 – 25.5
0 15.6
Dummer et al. [5] 1990 UK <0.1 15–16 50.1 5.71
26.2 11.8
Nunn et al. [6] 1992 UK <0.2 15 64.1 38.7
– 57.5
1.0 78.9 59
– 83.9
1.0–1.3 83.9 66.2
– 81.5
Fyffe et al. [7] 1996 UK – 13–14 48.7 –
Rugg-Gunn et al. [8] 1997 Saudi Arabia 0.25 14 75 –
0.80 82 –
2.71 93 –
Hiller et al. [9] 1998 Germany <0.02 8–10 39.9
Dini et al. [10] 2000 Brazil 0.7 9–10 26.1 –
Jalevik et al. [11] 2001 Sweden Low 7–8 33.3 –
Zagdwon et al. [12] 2002 UK <0.1 7 14.5 7.2
Ekanayake and 2003 Sri Lanka <0.3 14 29 –
van der Hoek [13] 0.3–0.5 35
0.5–0.7 43 –
>0.7 57 –
Cochran et al. [14] 2004 Finland <0.01 8 59 –
Greece <0.01 43 –
Iceland 0.05 54 –
Portugal 0.08 49 –
UK <0.1 48 –
The Netherlands 0.13 70 –
Ireland 1.0 69 –
Mackay and Thomson 2005 New Zealand – 9–10 51.6 –
[15]
Balmer et al. [16] 2005 UK <0.1 8–16 – 27.3
Australia 0.9–1.1 51.6
Wong et al. [17] 2006 Hong Kong 1.0 (1983) 12 92.1 –
0.7 (1991) 55.8 –
0.5 (2001) 35.2 –
Hoffmann et al. [18] 2007 Brazil – 12 46.4 –
Muratbegovic et al. [19] 2008 Bosnia and <0.1 12 32.8 –
Herzegovina
Arrow [20] 2008 Australia 0.8 7 22 –
Kanagaratnam et al. 2009 New Zealand – 9 35a –
[21]
(continued)
Table 2.2 (continued)
F level Age Prevalence %

Author Year Country (ppm) (years) Mouth Tooth
Seow et al. [22] 2011 Australia 0.1 13.5b 58 –
Casanova-Rosado 2011 Mexico – 6–12 7.5 –
et al. [23]
Robles et al. [24] 2013 Spain 0.07 3–12 52 8.3
Vargas-Ferreira 2014 Brazil – 8–12 64 –
et al. [25]
a
Both fluoridated and non-fluoridated areas
b
Mean age
Fig. 2.1 Hypoplasia of the

maxillary central incisors
Fig. 2.2 Hypomineralization

and hypoplasia of the
maxillary and mandibular
incisor teeth
of the incisors, progressing to the cervical areas of the teeth [29]. However, there is
still limited understanding of how mineralization progresses across the crowns of
the teeth. This could be important in determining the timing of defects to relate to
specific disturbances caused by systemic disorders. Disturbances in the different
stages of enamel formation may result in a range of enamel defects with quite dif-
ferent clinical appearances and structural changes. Defective formation of the
enamel matrix results in hypoplasia, a quantitative defect, depicted by generalized
thinning or pitting types of defects (Fig. 2.1). Defective calcification of an otherwise
normal fully developed organic enamel matrix results in hypomineralization, a
qualitative defect (Fig. 2.2). This is seen clinically as changes in color and
Fig. 2.3 (a) Caries in the mandibular second primary molar has led to the intra-radicular infection
which has resulted in hypoplasia of the developing second premolar. (b) Hypoplasia of the maxil-
lary permanent canine as a consequence of infection of the primary predecessor. (c) Hypoplasia in
the form of missing enamel is exhibited by this mandibular second premolar following infection of
the primary second molar
translucency of the enamel and presents as enamel opacities which can be either
demarcated or diffuse [2, 30].
Although the etiology of enamel defects may be attributed to local, systemic,
genetic, or environmental factors, most are likely to be multifactorial in nature. This
makes it difficult to identify a single cause for many cases of DDE. The time frame
of exposure and the mechanism underpinning the causative factors determine the
presentation of these defects. Defects on a single tooth or only a few teeth suggest a
local etiological factor e.g. a defect in a permanent tooth due to damage (trauma or
infection) to its primary predecessor (Fig. 2.3a–c). Alternatively, a systemic factor
(both short and longer term) may affect all the teeth that are developing during the
time of the insult and lead to what is described as a chronological defect. Genetic
factors can be considered separately. Defects caused by genetic factors are most
often (although not always) generalized in distribution, affecting both the primary
and permanent dentitions. They may present as either enamel defects alone as seen
in amelogenesis imperfecta (see Chap. 5) or as enamel defects associated with other

general genetic disorders/syndromes (see Chap. 4).
Enamel defects can be classified clinically as demarcated and diffuse opacities
and hypoplasia. The location of isolated defects depends on the stage of amelogen-
esis at the time of the insult or injury [31]. The general consensus regarding the etiol-
ogy of isolated opacities, which may be demarcated or diffuse and present as white,
creamy, or yellow in color, is that amelogenesis is affected by a disturbance during
the mineralization phase. It remains unclear why this would involve only an isolated
patch of enamel on the crown and not the whole surface. Conversely, hypoplasia
occurs when there is a disturbance during the secretory stage of amelogenesis while
the enamel is only partly mineralized. Thus, enamel defects with similar presenta-
tions may have been caused by a variety of etiological factors. Furthermore, the same
etiological factor can produce enamel defects with different presentations depending
on the timing of the insult. Examples of this are commonly seen following primary
tooth trauma. When a maxillary anterior primary tooth is intruded in infancy (during
the first year of life), the crown of the permanent successor may suffer severe struc-
tural damage with missing enamel and even dilaceration of the root or the crown,
while an intrusion in the later preschool years may only cause an isolated labial
hypomineralized enamel opacity on the permanent successor (Fig. 2.4a, b).
Fig. 2.4 (a) Hypoplasia of

the maxillary permanent
incisor tooth as a conse-
quence of trauma to the
predecessor. (b)
Hypomineralization and
hypoplasia of the maxillary
central incisor teeth as a
consequence of trauma to the
predecessor
Determining the Etiology
Based on the number of teeth affected, the possible etiological factors for DDE in
permanent teeth can be categorized as being local or general. However the evidence
is equivocal, with the majority of published reports being animal studies or case
reports of children with specific systemic disorders. The putative etiological factors
reported in the literature are summarized in Table 2.3. Only a few of these factors
have good evidence supporting a direct causal effect, e.g., trauma to a primary pre-
decessor or high levels of ingested fluoride during early childhood.
Localized Enamel Defects
When only one or few adjacent teeth exhibit an enamel defect, it is usually con-
sidered to be caused by a very localized or isolated factor rather than a more
generalized systemic or genetic factor [32]. The most common causes of localized
enamel defects are trauma, chronic radicular infection resulting from pulpal
necrosis in a primary predecessor tooth, surgery in the adjacent area or radiation
therapy. Other isolated defects with incompletely formed enamel such as those
associated with dens invaginatus and dens evaginatus may be due to a genetic
influence in certain teeth.
Intrusive and lateral luxation injuries to the primary teeth often result in enamel
defects in the succedaneous permanent teeth [33, 34]. This occurs most often in the
anterior teeth as they are more likely to suffer the direct impact of trauma from fall-
ing or being struck by an object than the posterior teeth. The severe consequences
arise because of the direct or nearly direct impact of the apex of the root of a primary
incisor on the crown or follicle of the developing permanent successor or may occur
as a consequence of post-traumatic complications of inflammation and infection.
Furthermore, if the trauma to the primary tooth leads to pulpal necrosis, then there
is a greater likelihood of enamel defects occurring in the succedaneous permanent
tooth. This can also occur following severe dental caries with pulp exposure leading
to untreated chronic infection [35]. Surgical procedures such as extraction of pri-
mary teeth, removal of supernumerary teeth, cleft palate repair or distraction osteo-
genesis have all been reported to cause localized enamel defects in the succedaneous
or adjacent permanent teeth [36–39]. Untreated carious lesions extending into the
pulp of primary teeth may result in pulpal necrosis and infection which may result
in DDE in the succedaneous permanent teeth (Fig. 2.3) [40–42]. The reported
defects have ranged from demarcated opacities to hypoplastic defects [43].
Generalized Enamel Defects
Generalized enamel defects are those defects that are seen either on the crowns of
groups of teeth or in all the teeth. As mentioned previously, the stage of amelogen-
esis in the particular tooth germ at the time of the insult or injury is often critical to
the resulting location and type of enamel defect. The timing of the disturbances
Table 2.3 List of etiological factors, reported in the literature, responsible for the formation of
enamel defects in the permanent dentition
Systemic
Local Perinatal and neonatal Postnatal Hereditary conditions
Trauma Neonatal Nutritional and 22q11 deletion syndrome
Primary tooth hypocalcemia gastrointestinal
Surgery disturbances
Distraction resulting in
osteogenesis hypocalcemia and
Tooth forceps vitamin D
deficiency
Chronic periapical Severe perinatal and Bacterial and viral Autoimmune
infection in a primary neonatal hypoxic infections polyendocrinopathy-
tooth injury associated with candidiasis-ectodermal
high fever dystrophy
Cleft lip and palate Prolonged delivery Exanthematous Candidiasis
diseases endocrinopathy syndrome
Radiation Prematurity Juvenile Cleidocranial dysostosis
hypothyroidism
Burns Low birth weight Hypothyroidism Celiac disease
Osteomyelitis Twins Hypogonadism Congenital adrenal
hyperplasia
Jaw fracture Cerebral injury Phenylketonuria Congenital contractual
arachnodactyly
Neurological Alkaptonuria Congenital unilateral facial
disorders hypoplasia
Hyperbilirubinemia Renal disorders Ectodermal dysplasias
Prolonged neonatal Congenital heart Ehlers-Danlos syndrome
diarrhea and vomiting disease
Severe neonatal Congenital allergy Epidermolysis bullosa
infections
High fever Oxalosis Focal dermal hypoplasia
Mercury poisoning Heimler’s syndrome
(acrodynia)
Fluoride Hypoparathyroidism
Prolonged use of Ichthyosis vulgaris
medicines
Prolonged diarrhea Lacrimo-auriculo-dento-
and vomiting digital syndrome
Radiation and Morquio syndrome
cytotoxic therapy Mucopolysaccharidosis
Oculodentodigital
dysplasia
Orodigitofacial dysostosis
Prader-Willi syndrome
Pseudohypoparathyroidism
Seckel syndrome
Tricho-dento-osseous
syndrome
Tuberous sclerosis
Vitamin D-resistant rickets
William’s syndrome
during tooth morphogenesis will determine the location and type of defects and the
number of teeth that will be affected. Homologous pairs of teeth will usually have
enamel defects in similar locations although the severity of the defects may not
always be the same suggesting that even homologous teeth do not always mineralize
at exactly the same rate. As the process of enamel development occurs in the differ-
ent tooth types over different developmental times, the locations of enamel defects
will differ between different homologous pairs of teeth [44]. Developmental defects
with this type of distribution are referred to as generalized defects of enamel and
may be caused by environmental factors or systemic conditions that have either a
defined time of influence or an ongoing influence throughout childhood, or they
may be caused by genetic factors. These conditions and their association with DDE
are discussed more fully in Chaps. 4 and 5.
Environmental Factors
Several environmental factors have been associated with DDE. These are believed
to cause systemic disturbances that affect enamel development rather than the envi-
ronmental agent affecting the ameloblasts directly. Environmental agents such as
lead, mercury, bisphenol A (an endocrine-disrupting chemical), some drugs such as
anticancer agents and tetracycline and some trace elements including fluoride and
strontium have been implicated in DDE. The systemic ingestion of these chemical
substances may exert an adverse effect on enamel formation during and after fetal
development [45, 46]. Exposure to such substances during amelogenesis may result
in the formation of defective enamel depending on the stage of enamel develop-
ment, the timing of exposure, the length of exposure and the underlying health of
the individual [47]. It should be remembered that some of the substances also have
a very positive effect, such as the ingestion of low levels of fluoride to improve
enamel maturation and decrease dental caries risk.
DDE arising from excess fluoride ingestion have been found in areas with high
natural levels of fluoride in the drinking water. Ingestion of excess fluoride during
tooth development can result in dental fluorosis, a form of enamel hypomineral-
ization where the white striations contain less mineral and retain more develop-
mental enamel proteins. The hypomineralization can vary from minor white
striations to small or more extensive opacities [48, 49]. The first 3 years of life is
generally understood to be the window of maximum susceptibility for the devel-
opment of fluorosis in the permanent maxillary central incisor teeth [50].
Nevertheless, for the whole permanent dentition, excluding the third molars, the
first 6–8 years of life is an important period when exposure to appropriate levels
of fluoride as defined in local guidelines should be followed [51]. Fluorotic hypo-
mineralization defects do have specific characteristics which allow them to be
differentiated from defects caused by other factors [52], and this can be useful for
the clinician to consider when diagnosing DDE. The characteristic lesions in fluo-
rosis are dull and chalky in appearance; they may vary in color from chalky white,
yellow, or brown, and in some cases there are small pits which accumulate organic
matter producing yellow to brown spots (Fig. 2.5). When diagnosing DDE that
Fig. 2.5 (a) Fluorosis is

a
evident in this permanent
dentition of a child who was
brought up in an area with
9 ppm of fluoride in the
drinking water. (b) An
example of less severe
fluorosis
may be related to fluoride, a careful history of total fluoride ingestion as well as

medical and developmental histories should be taken for the appropriate develop-
mental period of the affected teeth. Another trace element that can have an influ-
ence on the development of hypomineralization in enamel is strontium which has
been shown to be associated with enamel hypomineralization similar to that
caused by excess fluoride [53].
Several animal experiments have shown that teeth are very sensitive to the effects
of dioxins [54]. The most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-para-dioxin
(TCDD), arrests degradation and/or removal of enamel matrix proteins which is a
pre-requisite for the completion of enamel mineralization [55]. It has been hypothe-
sized that prolonged breast-feeding might increase the risk of DDE due to the envi-
ronmental contamination of breast milk with dioxins or dioxin-like compounds [56,
57]. A dose-response relationship between high levels of dioxins or polychlorinated
biphenyls (PCBs) exposure (serum concentration) and DDE in permanent teeth has
been reported [58, 59]. However the evidence remains mixed with other studies
reporting contradictory findings [11] and more recent studies failing to identify any
correlation between DDE in children living in areas polluted by dioxins and in those
living in areas with low pollution [60, 61]. It has also been reported that there is an
increase in incidence of diffuse white/creamy mottling of enamel with elevated lev-
els of chemicals such as fluorine, ammonia and sulfur in the atmosphere [62]; hyper-
vitaminosis D [63]; chronic lead poisoning [64]; diphosphonate poisoning [65]; and
polychlorinated biphenyl poisoning [66]. Antineoplastic therapy in the form of radia-
tion treatment and/or chemotherapy can affect any cells including ameloblasts and
consequently lead to DDE [67]. It has been reported that central nervous system
irradiation with scattered irradiation of 0.72–1.44 Gy to the dental arches can result
in a range of enamel defects in developing permanent teeth [68, 69].
Genetic Disorders
Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders that

affects the development of dental enamel resulting in varying degrees of hypoplasia,
hypomineralization and/or hypomaturation [70]. A single-gene defect can occur as
X-linked, autosomal dominant, or autosomal recessive inheritance. There is evi-
dence that AI may present as part of a hereditary syndrome, examples of which are
epidermolysis bullosa [71, 72], pseudohypoparathyroidism [73], and tricho-dento-
osseous syndrome [74]. See Chaps. 4 and 5.
Systemic Conditions
It has been suggested that perinatal and postnatal problems, hypoxia and malnutri-
tion may be related to the occurrence of DDE in permanent teeth. However, the
mechanisms are not clearly understood and it is difficult to link any of the condi-
tions directly to the defects. Children with low birth weights have been shown to
be more at risk for developing DDE in their primary teeth. However the evidence
is weaker in relation to the permanent dentition [75]. Similarly, problems at the
time of delivery such as caesarean section and labor in excess of 20 h and poor
respiratory response in the postnatal period (hypoxia and respiratory diseases in
early childhood) have all been linked with the occurrence of DDE, but currently
there is insufficient evidence to be confident about any of these as direct causes of
DDE [76].
There are numerous reports of DDE in the permanent dentition being associated
with diseases and infectious conditions occurring in early childhood. Infectious dis-
eases occurring during early childhood that may be related to DDE include chick-
enpox, asthma, measles, mumps, scarlet fever, exanthematous fevers, pneumonia
and urinary tract infections. Other conditions such as convulsions, tuberculosis,
diphtheria, whooping cough, otitis media, bulbar polio with encephalitis, gastroin-
testinal disturbances, cyanotic congenital heart disease, neurological disorders and
renal disorders have also all been mentioned in association with DDE.
Vitamin D deficiency, hypocalcemia, hypophosphatemia and hyperparathyroid-
ism have also all be implicated in DDE in the permanent dentition. Vitamin
D-dependent rickets (VDDR) is a condition which appears to be increasing in prev-
alence either due to vitamin D deficiency in the mother during pregnancy or vitamin
D deficiency in the young child [77]. Vitamin D deficiency contributes to the devel-
opment of hypocalcemia and hypophosphatemia which is then compounded by sec-
ondary hyperparathyroidism which in turn increases renal inorganic phosphate (Pi)
clearance, effectively worsening the hypophosphatemia. Consequently the low
concentrations of Ca2+ and Pi prevent proper mineralization of the organic bone

matrix and this also leads to defects in enamel mineralization [78].
There is a growing body of literature reporting associations between DDE and
systemic conditions such as celiac disease, cystic fibrosis and tuberous sclerosis
though the mechanisms involved are often not fully understood [79–82].
Hypocalcemia has also associated with the occurrence of enamel hypoplasia in the
permanent dentition in hereditary vitamin D-resistant rickets, X-linked hypophos-
phatemia, and hypoparathyroidism [83].
Despite the numerous reports of DDE in association with all of these conditions,
there is little strong evidence to support any condition as being a primary etiological
agent responsible for the formation of the enamel defects in the permanent
dentition.
Summary
The prevalence of DDE in the permanent dentition (in developed countries) is

reported to be between 9 and 68 %. This wide variation can be attributed to the use
of different criteria and terminologies to describe enamel defects. The etiology of
enamel defects may be local or systemic, genetic, or acquired in origin. The clinical
presentation of DDE varies greatly depending on the etiology and severity. Single-
tooth defects can be attributed to a local factor, whereas in those of systemic etiol-
ogy many or all of the teeth that are developing during the time of influence of the
etiological factor are affected (chronological defects). Defects with a genetic etiol-
ogy form a separate entity, usually affecting both the primary and permanent teeth.
Identifying the presence of DDE and establishing a diagnosis are essential to inform
appropriate treatment planning in both the short and longer term (see Chap. 8).
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Molar Incisor Hypomineralization
and Hypomineralized Second Primary 3
Molars: Diagnosis, Prevalence,
and Etiology
Karin L. Weerheijm, Marlies E.C. Elfrink,

and Nicky Kilpatrick
Abstract
Molar incisor hypomineralization (MIH) is a term used to describe a specific
clinical entity in which there are demarcated opacities in erupting first perma-
nent molars, frequently in combination with similar opacities in permanent inci-
sors. Recently, comparable lesions have been reported in second primary molars
and are referred to as hypomineralized second primary molars (HSPM). This
chapter describes the diagnosis, etiology, and prevalence of MIH and HSPM
and discusses the clinical characteristics and implications of this subgroup of
DDE. Given the specific distribution of the developmental defects associated
with MIH (and HSPM), the timing of any causative environmental disruption
can be hypothesized to be between the 18th week of pregnancy and around
3–5 years of age. However, the evidence surrounding specific factors remains
weak, not least because of a lack of consensus regarding assessment protocols
and limited understanding as to the exact pathogenesis. Etiology seems to be
multifactorial, and the etiological factors can be found in the pre-, peri-, and
postnatal period. The literature suggests the worldwide prevalence of MIH varies
K.L. Weerheijm, PhD (*)

Department of Cariology Endodontology Pedodontology, Academic Centre for Dentistry (ACTA),
Paediatric Dentist, Kindertand Zuid and Member Paediatric Research Project (PREP),
Milletstraat 28 hs, Amsterdam 1077 ZE, The Netherlands
M.E.C. Elfrink, PhD
Department of Cariology Endodontology Pedodontology, Academic Centre for Dentistry (ACTA),
Paediatric Dentist, Mondzorgcentrum Nijverdal and Member Paediatric
Research Project (PREP), Stationsstraat 7, Nijverdal 7443 BX, The Netherlands
N. Kilpatrick, BDS, PhD
Cleft and Craniofacial Research, Murdoch Childrens Research Institute,
Flemington Road, Parkville, Melbourne, VIC 3052, Australia

32 K.L. Weerheijm et al.
between 2.8 % and 44 %, whereas for HSPM, figures of between 4.9 and 9.0 %
have been reported. The presence of HSPM and demarcated opacities in erupt-
ing permanent incisors represents risk indicators for subsequent MIH. As MIH is
associated with hypersensitive teeth, posteruptive loss of enamel and rapid caries
progression early diagnosis is clinically very important.
Introduction
Despite a general decline in caries prevalence over the past 30 years, there remains a
subgroup of children in whom rapid caries progression, particularly affecting the first
permanent and second deciduous molars, still occurs. These children present fre-
quently to dentists who are confronted with large defects during or soon after the
eruption of the affected teeth. In 1987 Koch et al. [1] reported the prevalence of
hypomineralized first permanent molars in different Swedish birth cohorts. These
molars have subsequently been referred to in the literature, as non-fluoride hypomin-
eralization, idiopathic enamel hypomineralization, non-endemic mottling of enamel,
or cheese molars [2]. The phenomenon, known as molar incisor hypomineralization
(MIH) was first recognized in 2001 and defined as hypomineralization of one to four
first permanent molars often in combination with affected permanent incisors
(Fig. 3.1) [3]. Subsequently, MIH-like lesions have been recognized in second pri-
mary molars (Fig. 3.2) leading to the description of hypomineralized second primary
molars (HSPM) [4] also called deciduous molar hypomineralization (DMH) [5].
Fig. 3.1 Example of MIH with molar as well as incisor opacities. Notice the white demarcated
opacity 11, yellow demarcated opacity 21. Yellow brown demarcated opacities erupting 46, brown
demarcated opacities with occlusal buccal posteruptive enamel loss 36, as well as demarcated yel-
low brown opacities in erupting 16 and 26 (Courtesy of Dr. H. Pohlen, Alsdorf, Germany)
3 Molar Incisor Hypomineralization 33
Fig. 3.2 Mild HSPM in the

85 while the erupting 46
shows already severe MIH
(posteruptive enamel loss on
both mesial cusps)
Diagnostic Criteria
In 2003, following a consensus meeting of the European Academy of Pediatric

Dentistry (EAPD), criteria for epidemiological studies of MIH were developed
including recognition of the potential for MIH-like hypomineralization defects to
occur in second primary molars [4]. In 2009 in Helsinki, the EAPD updated these
criteria [6] such that currently the criteria for MIH include demarcated opacities,
posteruptive breakdown (or PEB) and both atypical restorations and extractions of
the permanent molars and/or incisors. HSPM is defined similarly as hypomineral-
ization of one to four second primary molars [7, 8]. To diagnose HSPM, the same
criteria are used as for MIH with “atypical caries” being included in addition to
“atypical restorations.” Especially in the primary dentition, cavities may not be
restored in certain populations.
To arrive at a diagnosis of MIH, it is important to identify white, yellow or brown
demarcated opacities on at least one first permanent molar. The greater the number
of affected molars in an individual patient the greater the risk that the incisors will
also be affected [2, 9]. The presence of opacities on the permanent incisors is not
mandatory for the diagnosis of MIH. However, opacities that only occur on perma-
nent incisors do not lead to a diagnosis of MIH. This is because the etiology of
opacities confined to permanent incisors is likely to be different to that of the more
widespread MIH condition. Traumatic injuries (particularly intrusive ones) to pri-
mary incisors impact on the developing tooth germs and commonly lead to local-
ized anomalies of the permanent successors [2, 4, 10].
Clinical Features
MIH is a hypomineralization defect affecting the quality (as opposed to the quan-
tity) of the enamel. It is identified visually as an alteration in translucency of the
enamel, with a sharp demarcation between the affected and sound enamel, known
as a demarcated opacity. The color of the hypomineralized area is white, yellow or
brown and the area has a dull (porous) or shiny surface appearance (Fig. 3.3). MIH
is not only variable in expression between patients but also within an individual
patient. The number of affected first permanent molars per child can vary from one
to four and the expression of the defects may vary from molar to molar. Within one
patient, intact demarcated opacities can be found in one molar, while in another
molar in the same patient, the porous enamel is already broken down (asymmetrical
appearance). The porous brittle enamel can easily chip off under the masticatory
forces very soon after eruption. This chipping off has been described in the litera-
ture as posteruptive enamel loss or PEB [4]. Sometimes the loss of enamel in PEB
can occur so rapidly after eruption that it seems as if it was not formed initially
(Fig. 3.4). However, it is important that the clinician distinguishes between PEB and
hypoplasia. Hypoplasia is a primary quantitative defect of the enamel that occurs
during tooth development. The resulting enamel may be thin or actually missing and
may be characterized as pits or grooves across the tooth surface. The color and loca-
tion of the demarcated opacities in MIH-affected molars are indicative of the
Fig. 3.3 Yellow to brown

demarcated opacity covering
almost the entire occlusal
surface of the recently
erupted 16 (Courtesy of Dr.
M. van Ulsen, Amsterdam,
the Netherlands)
Fig. 3.4 Tooth 16 with posteruptive enamel loss and opacity on the palatal surface. The same
tooth after 1 year posteruptive enamel loss with cavity formation
Fig. 3.5 Incisors with

demarcated opacities in a
child with severe
MIH. Notice the white
opacities in teeth 31 and 41,
the light yellow/white
opacities in teeth 11 and 21,
and the dark yellow opacities
in the 32 and 42
relative risk for PEB; brown, dull, and porous opacities on cuspal tips are thought to
be weaker than white and shiny ones on smooth surfaces and therefore more vulner-
able to chipping [9].
The clinical appearance of the location, size, and form of the HSPM- and MIH-
related carious lesions and restorations often do not fit with normal caries distribu-
tion patterns. These lesions and restorations have been reported as atypical caries or
atypical restorations in some epidemiological studies [4]. When the incisors also
show opacities most commonly these remain intact because the chewing forces have
less impact on incisors compared with molars (Fig. 3.5).
Both MIH and HSPM are very inconvenient for the child. The child may experi-
ence pain and sensitivity from the affected teeth particularly when exposed to hot
and cold foods and drinks. Even if the (porous) hypomineralized enamel is intact,
toothbrushing can cause sensitivity [2, 3]. In the event of PEB caries can progress
rapidly increasing the risk of toothache. Pain-free treatment, which can be challeng-
ing because the teeth are sensitive, is important to avoid behavioral management
problems or the development of dental anxiety in the future [11].
Etiology of MIH
Tooth development is under strict genetic control; however it is also very sensitive to
environmental changes. Ameloblasts, which are highly specialized calcium-
transporting cells, play an integral role in all three of the stages of enamel formation:
matrix formation, initial calcification and final maturation [12]. If ameloblast function
is disrupted during the secretory phase, there will be irreversible damage to the cells
and the teeth are characterized by a deficiency of tooth substance that ranges from
minor pits and groves to total absence of enamel; this is termed enamel hypoplasia and
is a quantitative defect. If, however, disruption of ameloblasts occurs later during
either the calcification or maturation phase, then the teeth will manifest in a qualitative
defect termed enamel hypomineralization and can present as an enamel opacity [13].
As discussed in Chaps. 1 and 2, ameloblasts are highly susceptible to environ-
mental disruptions leading to developmental defects in the enamel (DDE).
Depending on the timing of the disruption, which can be from the time the first
primary tooth starts to form (15–19 weeks in utero) to the completion of the matura-
tion of the third permanent molar (around 12 years of age), the defects manifest
differently across either dentition. However MIH is a very distinct form of DDE in
which the enamel of the first permanent molars (+/− the incisors) is specifically
hypomineralized. First permanent molars begin to develop in the fourth month in
utero, but calcification does not start until around the time of birth. For an environ-
mental disruption to contribute to MIH specifically, it would therefore likely occur
from sometime around the time of birth to 3–5 years of age by which time matura-
tion of the coronal enamel on the first permanent molars (and incisors) is complete.
Recent in vitro studies have suggested an even narrower window of susceptibility
around 6–8 months of age based upon the histological, mechanical, and chemical
properties of affected first molar teeth [14, 15]. In general, the putative causes of
MIH are similar to those identified in Chaps. 1 and 2 in association with more gen-
eralized DDE in both the primary and permanent dentitions. Table 3.1 is a summary
of the possible etiological factors for MIH. The factors are divided into pre-, peri-
and postnatal factors with medical problems being commonly mentioned. Fluoride
does not appear to influence the occurrence of MIH [25].
The strength of the evidence surrounding the etiology of MIH specifically
remains weak [18, 25]. There are a number of reasons for this including:
(i) The historical lack of consensus surrounding both the definition of MIH and how
to record it, leading to the use of a wide variety of often unvalidated indices.
(ii) Reliance on retrospective data either using parental recall of the perinatal
period or, slightly more reliable but nevertheless generally incomplete, retro-
spective chart reviews.
Table 3.1 Factors putatively associated with MIH

Factor Reference
Prenatal
Lifestyle Health Maternal illness or infection [16, 17]
Maternal hypocalcemia [16, 17]
Nutrition [16, 18, 19]
Perinatal
Health Infant hypoxia [16, 18, 20, 21]
Very low birth weight [22, 23]
Premature birth [18, 21, 24]
Calcium shortage [16, 18, 19]
Misc medical problems [18]
Postnatal
Lifestyle Breastfeeding [14, 17, 18, 21,
25–27]
Nutrition [14, 19]
Calcium shortage [16, 18, 19]
Environment Dioxins and polychlorinated [1, 18, 25, 26, 28–35]
bisphenols
Environmental pollution [31, 33]
Health Childhood illnesses (in general) [16–18, 21, 25, 26,
36]
Chicken pox and other viral infections [17]
Otitis media [21, 26]
Asthma, lung problems, allergy [17, 21, 26, 37]
Fevers (irrespective of cause) [21, 38]
Medications (in general) [17, 18, 25, 26, 39]
Antibiotics [17, 39–41]
Antiasthmatic medication [42]
(iii) Under-recording of the problem. First permanent molars affected by MIH are
susceptible to both PEB and rapid carious attack shortly after emerging into
the oral cavity. Many studies exclude restored or carious teeth from the assess-
ment which is likely to lead to an under-reporting of MIH, while others may
incorrectly classify PEB as hypoplasia. Similarly, severely affected molars
often require early extraction. Many studies include population samples of
children over 10 years old and few make any attempt to discover why missing
teeth have been extracted – this is also likely to lead to under-reporting of
MIH.
A further confounding factor when attempting to unravel the etiology of MIH is

how to account for the typically asymmetric distribution of the hypomineralized
lesions in MIH. This makes it difficult to attribute definitive causality between an
environmental disruption and the presence of MIH. This may be explained in part
by variations in the timing of mineralization of homologous pairs of teeth i.e. lower
second molars [43]. It is also possible that there are genetic factors [44, 45] and
local environmental factors within developing tooth germs themselves that may pre-
dispose to MIH. As understanding of the structure and composition of MIH-affected
enamel evolves the etiology of this condition will become clearer but is almost
certainly multifactorial and complex.
Etiology of HSPM
As with MIH, the etiology of HSPM appears to be multifactorial. Three studies have
been published to date with the pre- and perinatal factors being reportedly more
important in HSPM than in MIH [46–48]. Ninety-four percent of children with
HSPM have been reported to have at least one medical problem: 24.5 % occurring
prenatally, 45.3 % perinatally, and 9.4 % postnatally [46] with the greater the num-
ber of medical problems the greater the risk of HSPM. Furthermore, the ethnicity of
the child, maternal alcohol consumption during pregnancy, low birth weight and
fever episodes in the child’s first year of life have been identified as risk factors for
HSPM [47]. Conversely, use of medications during pregnancy (specifically antibiot-
ics and antiasthmatic and anti-allergic medications) does not seem to influence the
occurrence of HSPM [47, 48].
Prevalence of MIH
The reported prevalence of MIH varies between 2.8 and 44 %. However despite the
publication of recommended diagnostic criteria for [4, 6], the lack of consensus sur-
rounding examination protocols, choice of index and population characteristics
means that it is still hard to make valid comparisons between the various epidemio-
logical studies [14, 25]. Table 3.2 summarizes the reported prevalence of MIH
worldwide including the indices used in each study. In addition to differences in
reported prevalence of MIH between countries, differences are also noted across
birth year. For example, in the study of Koch et al. [1], the prevalence of MIH varied
between 4.4 and 15.4 % across the different birth years with a peak in prevalence for
those children born in 1970. These data were reproduced later by Jalevik et al. in
Swedish children born in 1990 [26]. Most studies show an equal distribution of
MIH between sexes [26, 55, 71] and, although Leppäniemi et al. [55] found a pre-
disposition for MIH in the upper jaw, most studies fail to show any quadrant predi-
lection for MIH defects [9, 26, 68, 71].
Prevalence of HSPM
Compared with MIH, there are very few prevalence studies on HSPM. Table 3.3
summarizes the available data which suggests that the prevalence of HSPM varies
between 4.9 and 9.0 %. HSPM is also equally distributed between sexes and arches
[7]. HSPM is now also recognized as a risk factor and clinical indicator for MIH
(OR: 4.4 (95 % CI: 3.1–6.4) [72]. Even relatively mild expressions of HSPM
increase the chances of future MIH (Fig. 3.2) [72]. In children with mild HSPM, the
Table 3.2 Overview of the prevalence studies on MIH

Country Prevalence (%) Score criteria Reference
Australia 22 mDDE Arrow [49]
Australia 44 mDDE Balmer et al. [50]
Bosnia and Herzegovina 12.3 EAPD 2003 Muratbegovic et al. [51]
Brazil 40.2 EAPD 2003 Soviero et al. [52]
Brazil 19.8 EAPD 2003 da Costa-Silva et al. [53]
China/Hong Kong 2.8 EAPD 2003 Cho et al. [54]
Denmark 37.3 EAPD 2003 Wogelius et al. [42]
Finland 17 Alaluusua 1996 Alaluusua et al. [30]
Finland 19.3 Alaluusua 1996 Leppaniemi et al. [55]
Germany 9.9 EAPD 2003 Petrou et al. [56]
Greece 10.2 EAPD 2003 Lygidakis et al. [16]
India 9.2 EAPD 2003 Parikh et al. [57]
Iran 20.2 EAPD 2003 Ghanim et al. [58]
Iraq 21.5 EAPD 2003 Ghanim et al. [59]
Italy 13.7 MIH 2001 Calderara et al. [60]
Jordan 17.6 EAPD 2003 Zawaideh et al. [61]
Libia 2.9 MIH 2001 Fteita et al. [62]
Lithuania 9.7 EAPD 2003 Jasulaityte et al. [63]
New Zealand 14.9 mDDE Mahoney and Morrison [64]
New Zealand 18.8 mDDE Mahoney and Morrison [65]
Spain 17.8 EAPD 2003 Martínez Gómez et al. [66]
Spain 21.8 EAPD 2003 Garcia-Margarit et al. [67]
Sweden 4.4–15.4 Koch 1987 Koch et al. [1]
Sweden 18.4 mDDE Jalevik et al. [26]
The Netherlands 9.7 Weerheijm 2001 Weerheijm et al. [68]
The Netherlands 14.25 MIH 2001 Jasulaityte et al. [69]
Turkey 14.9 EAPD 2003 Kuscu et al. [70]
Table 3.3 Overview of the Country Prevalence (%) Reference

prevalence studies on HSPM
Iraq 6.6 Ghanim et al. [46]
The Netherlands 4.9 Elfrink et al. [7]
The Netherlands 9.0 Elfrink et al. [72]
odds ratio (OR) for MIH was 5.3 (95 % CI: 2.9–9.4) and in children with severe
HSPM, the OR was 4.0 (95 % CI: 2.6–6.3).
Clinical Implications
Opacities on second primary molars (HSPM) and erupting permanent incisors are
potential indicators for MIH. While MIH cannot be confirmed until the complete
eruption of all four first permanent molars the dental team should be alert for such
lesions as soon as teeth erupt. In the case of the second primary molars, this is around
2 years of age. This emphasizes the importance of raising parental awareness of oral
health and establishing a dental home early in their child’s life. Understanding these
lesions as predictors of MIH means that it is possible to inform patients of the poten-
tial implications and need for proactive prevention and dental management. More
frequent dental checkups may be needed during the period of first permanent molar
eruption [72]. When opacities on newly erupting first permanent molars are first
identified, it is important to discuss the diagnosis of MIH not only because hypomin-
eralized teeth cause discomfort and develop caries more easily but also because the
permanent incisors may be affected. This can prepare the individual child and their
parents for future esthetic issues that may become evident once the incisors erupt.
However it is also equally important to reassure affected children and their parents
that permanent teeth other than first molars and incisors are unlikely to be hypomin-
eralized because the timing of development of the remainder of the permanent denti-
tion does not coincide with that of the first molars and incisors.
Future Goals
In most countries where more than one prevalence study has been performed (see
Tables 3.2 and 3.3), the more recent study shows a higher prevalence. It is unknown
if this is an expression of increasing prevalence or an example of improved recogni-
tion of this particular dental enamel defect. Data from around the world and from
different birth cohorts are important not only for future dental service planning but
also in helping the search for better understanding of the etiological factors involved
in MIH and HSPM. From that point of view it now seems advisable to incorporate
assessment of MIH and HSPM prevalence figures with standardized score criteria
into national epidemiological caries prevalence studies in order to answer the ques-
tion as to whether the prevalence of MIH and HSPM is stable or whether it increases
or decreases over time.
Conclusion
HSPM and MIH require early diagnosis. HSPM as well as demarcated opacities
on erupting permanent incisors can be used as predictor for MIH though not
exclusively. Children who experience one or more of the possible etiological fac-
tors need to be checked for HSPM and/or MIH. Children with HSPM or MIH
need increased surveillance by the dental team including more frequent dental
checkups and additional preventive advice particularly around the time of erup-
tion of the second primary and first permanent molars. Prevention and treatment
options for MIH and HSPM will be addressed further in Chaps. 8, 9, 10 and 11.
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Syndromes and Diseases Associated
with Developmental Defects of Enamel 4
Mike Harrison, Angus Cameron, and Nicky Kilpatrick
Abstract
Some patients have what may be described as “syndromic teeth.” The size, number
or crown/root morphology can indicate that the patient is affected by a recognized
malformation syndrome. Developmental defects of enamel (DDE) can sometimes
be part of a constellation of developmental changes elsewhere in the body and may
even provide diagnostic clues. If the underlying condition includes processes that
may affect enamel formation in more generalized, non-genetic ways, it can be dif-
ficult to be precise about the mechanism of the defect. Examples include renal dis-
ease and congenital cardiac defects, both of which can be of genetic origin and
disturb enamel formation by genetic and/or pathological means. This section will
describe some diseases and syndromes reported to exhibit DDE, with some guid-
ance about whether they are likely to have direct or indirect association.
Introduction
As is discussed in other chapters (Chaps. 1, 2 and 5), developmental defects of

enamel (DDE) have been reported to occur in association with a wide range of sys-
temic conditions. For convenience this chapter is divided into diseases and
M. Harrison, BDS, MScD, MPhil (*)

Department of Pediatric Dentistry, Guy’s and St Thomas’ Dental Institute,
Floor 22 Guys Tower, Great Maze Pond, London SE1 9RT, UK
A. Cameron, BDS, MDSc
Department of Pediatric Dentistry, Westmead Hospital and The University of Sydney,
Darcy Rd, Westmead, NSW 2145, Australia

46 M. Harrison et al.
Systemic disease Genetic disease

Non-genetic effect on ameloblasts Non-genetic effect on ameloblasts Direct genetic effect on ameloblasts
Enamel defect
Fig. 4.1 Classification of the etiology of enamel defects in relation to systemic diseases or genetic
syndromes
syndromes, but in reality there is much overlap with many systemic diseases having
an identified genetic origin e.g. cystic fibrosis.
These disorders of enamel will be considered in three ways (see Fig. 4.1):
(i) Those presenting with systemic disease as a pathological but non-genetic effect
on ameloblasts
(ii) Those presenting with a genetic disease and with a similar pathological but
non-genetic effect on the ameloblasts
(iii) Those specific genetic diseases in which the affected gene is known to be
directly involved in amelogenesis
It is important to distinguish between the terms hypoplasia and hypomineraliza-

tion in the diagnosis of enamel defects. Hypoplasia is a defect in the quantity of the
enamel. It results from a disorder of amelogenesis during the appositional or initial
secretory stage of enamel formation. It may appear as thinner enamel, pits, or
grooves. Adjacent enamel may also be hypomineralized. Hypomineralization
relates to a deficiency in the quality of the enamel, presenting primarily as an opac-
ity (or porosity) in the enamel. This may be present superficially or through the full
thickness of the enamel. Most hypomineralization defects occur during the later
maturation phases of tooth development.
Systemic Disease with a Non-genetic Effect on Ameloblasts
Preterm and Low Birth Weight Infants
It is not uncommon for infants to be born as early as 25 weeks gestation and not
only to survive, but develop with relatively few physical or intellectual conse-
quences. However the stigmata of the preterm infant can manifest even in children
born up to 36 weeks, related to conditions including perinatal respiratory distress,
intracranial bleeds, pulmonary immaturity, persistent ductus arteriosus and ven-
tricular septal foramina, necrotizing enterocolitis and some debilitating infections.
Long-term ventilation via oral or nasal intubation, hyperbilirubinemia leading to
jaundice and suboptimal nutrition all contribute to the comorbidity. Neonatal
hypocalcemia presents in all newborn infants up to 48 h until the development of
4 Syndromes and Diseases Associated with Developmental Defects of Enamel 47
normal calcitonin and parathyroid hormone levels. However this hypocalcemia is

often more severe in preterm neonates resulting in altered calcification of the
enamel matrix.
The timing of development of the primary and permanent dentitions means that
amelogenesis in the primary dentition is particularly vulnerable to disturbances as a
consequence of prematurity. Thus, in the primary dentition, there is a direct association
between low birth weight (<1,500 g) and both enamel opacities and hypoplasia [1].
Although the actual process of mineralization of permanent dentition enamel
does not commence until around the time of a full-term birth, some studies have
reported an increased risk of enamel defects in the first permanent molars [2–4].
However, the strength of the evidence to support a causal relationship between pre-
term birth and DDE in the permanent dentition remains limited at this time [1].
Renal Disease
Renal function is essential in homeostatic regulation of the calcium and phosphate

salts needed for the formation of all mineralized tissues. Although odontogenesis is
notably different from osteogenesis its processes are equally susceptible to dysregu-
lation of mineralization resulting from renal failure. Hypoplastic horizontal enamel
defects are characteristic of acute renal disease in early childhood. The position of
the defects on the crowns of the permanent teeth is often strikingly coincident with
the age of the child at the onset of disease. Normal full-thickness enamel formation
will be seen following remission or resolution of the acute phase.
Nephrotic Syndrome
Nephrotic syndrome is a non-specific kidney disorder associated with damage to the

glomeruli which alters their capacity to filter substances transported in the blood.
Despite the term “syndrome” this is a heterogeneous range of conditions whose
genetic basis is currently not fully understood. It has been reported to cause hypo-
mineralization defects [5] though the mechanism is somewhat unclear. A failure of
the highly selective filtration in the glomerulus leads to heavy loss of albumin, lipids
and other proteins. Widespread edema is the initial feature but loss of macromole-
cules and binding proteins leads to significant morbidity and even mortality. The
primary cause of this edema is failure of water and salt excretion and it must be
presumed that this also disrupts calcium and phosphate homeostasis, resulting in
defects in tissues which are undergoing mineralization.
Celiac Disease
Enamel defects occur with varying severity in patients with celiac disease, an
immune-mediated disorder in which damage to the mucosa of the small intestine
Fig. 4.2 Grade I enamel defects in a 14-year-old girl diagnosed with celiac disease at the age of
9 years (Courtesy of Dr AK Natarajan, New Zealand)
occurs causing malabsorption when susceptible individuals ingest proline- and

glutamine-rich proteins (“gluten”) in wheat, rye, and barley [6]. The risk of enamel
defects has been reported to be higher with the presence of HLA-DR52–53 and DQ7,
human leukocyte antigens [7]. The prevalence has been reported in the primary den-
tition as between 5.8 and 13.3 % and in the permanent dentition between 9.5 and
95 % with incisors being the most commonly affected teeth [8–11]. This is not unex-
pected as the crowns of the incisors form in the first year of life when gluten is first
introduced into the diet. The severity of the defects is related to the length of time of
gluten exposure before the condition is diagnosed. Once gluten is removed from the
diet, symptoms will disappear but enamel defects will remain. The classification of
enamel defects in celiac disease is usually that reported by Aine in 1986; Grade 0
exhibits no defects; Grade I exhibits a color defect with cream, yellow, or brown
opacities; Grade II exhibits rough enamel surface with shallow horizontal grooves or
pits and may include opacities and discoloration; Grade III exhibits structural defects,
a rough surface, deep horizontal grooves, vertical pits and large discolored opacities;
and Grade IV exhibits severe structural defects with pointed cusp tips and/or thinned
uneven incisal edges. Usually defects can be detected in a pattern across all four
quadrants. Figure 4.2 shows a typical pattern of Grade I enamel defects in a 14-year-
old female diagnosed with celiac disease at 9 years of age.
There are two possible mechanisms underpinning the DDE lesions seen in celiac
disease; one relates to malabsorption leading to hypocalcemia, while the other sug-
gests that there may be an immune response to the ameloblasts [12]. Irrespective of
the mechanism, the pattern of the DDE should always be recorded carefully by cli-
nicians in all patients who have a diagnosis of celiac disease. Conversely when a
Fig. 4.3 (a) Shows the

a
clinical image and (b) radio-
graph of a 10-year-old treated
with chemotherapy and
radiotherapy for a hepatoblas-
toma age 2 years
pattern of specific enamel defects occurs and no other cause can be determined,
clinicians should consider celiac disease in the differential diagnosis. Questions in
the history should include occurrence of recurrent aphthous ulceration, abdominal
pain, diarrhea, poor weight gain, fatigue, anemia or a family history of celiac dis-
ease. A referral should be made to a pediatrician or gastroenterologist for testing
with a description of the oral signs that have been detected.
Childhood Oncology
The enamel organ is very sensitive to the toxic effects of chemotherapeutic agents
and radiation therapy. The effects of radiation may be attributable to both determin-
istic effects (non-stochastic, dose dependent) and stochastic effects (random, no
minimum dose). Agenesis, microdontia, and ridges of hypoplasia may be seen,
almost always with concomitant disturbances of dentin development and root mal-
formations in particular (Fig. 4.3a, b).
The leukemias are the most common group of childhood malignancies; thus the
effects of therapy on amelogenesis tend to be generalized. Therapy for solid tumors
such as brain and ocular lesions is often more targeted and more likely to affect one
side or even one quadrant. The severity of the defects will be determined primarily
by the age of the child when therapy is commenced and then by the type, intensity
and duration of therapy [13].
Genetic Systemic Disease with an Indirect Effect

on Amelogenesis
The processes of odontogenesis, including amelogenesis, are dependent on com-

plex temporal and spatial interaction between genes and gene products, the contem-
porary understanding of which is less than comprehensive. While this section
summarizes some monogenic diseases where the causative gene is currently not
thought to be involved in amelogenesis, there may be a future time when a direct
cause-and-effect model is identified.
Rickets
The term “rickets” has been traditionally used to describe the skeletal disease associ-
ated with deficiency in vitamin D, be that a dietary deficiency or one resulting from
insufficient exposure to sunlight. However more recently the term has been expanded
to include inherited metabolic bone diseases causing defects in mineral metabolism.
Advances in understanding the molecular basis of disorders of hard tissue formation
and regulation have led to discovery of specific genes and their protein products
which, when mutated, lead to specific bone diseases. As is often the case, where
skeletal bone metabolism is defective, odontogenesis is affected in some way [14].
Vitamin D-Dependent Rickets (VDDR)
Deficiency of vitamin D and calcium was a very common cause of rickets in the past.
However it almost disappeared in the Western world during the early twentieth century
thanks to the fortification of foods with vitamin D. More recently there has been a resur-
gence in the prevalence of VDDR which has been linked to inadequate exposure to
sunlight. The factors behind this remain putative but include heightened awareness of
the risk of skin cancer, cultural clothing practices leading to women being fully covered
and dark-skinned people living in northern (cloudy) climates with little daily sunlight.
Enamel and dentin defects have long been reported in VDDR, with hypoplastic
(often discolored) enamel, large pulp chambers, short roots and interglobular dentin
spaces [15]. These defects are closely linked to circulating levels of the active meta-
bolic form of vitamin D, namely 1,25-dihydroxyvitamin D3. Direct effects on the
enamel organ and odontoblasts can cause defects in both matrix secretion and min-
eralization resulting in hypoplastic enamel which may also be hypomineralized
(Fig. 4.4). Importantly early diagnosis of VDDR and appropriate dietary supple-
mentation can improve both skeletal and dental mineralization.
X-Linked Hypophosphatemic Rickets (XLHR)
While rare, XLHR is the most common cause of familial rickets with an inci-
dence of 1:20,000 births [16]. The disease is related to an isolated phosphate
Fig. 4.4 Vitamin

D-dependent rickets showing
hypoplastic enamel defects
transport defect caused by mutations in the PHEX gene that results in increased
inhibition of both skeletal and dental mineralization. This X-linked dominantly
inherited condition is characterized clinically by hypophosphatemia (reduced
phosphate level in the blood), growth retardation, rickets and well-recognized
dental manifestations. Initial descriptions of XLHR emphasized the poor clini-
cal response to vitamin D rather than the distinctive finding of marked hypo-
phosphatemia, hence the historical use of the term “vitamin D-resistant
rickets.”
As with some other familial forms of rickets, XLHR is associated with spontane-
ous dental abscesses which are probably associated with the thin, hypomineralized
dentin and large pulp chambers. The enamel in these conditions often appears mac-
roscopically normal though enamel hypoplasia, cracks and defects have been
reported [17]. The mechanism behind these enamel defects, which are reported to
occur in up to 28 % of XLHR affected individuals [18], is currently unclear; how-
ever they may well contribute to the apparently spontaneous nature of these
abscesses (Fig. 4.5a, b). The dental manifestations can be particularly miserable for
the affected individuals and are also difficult to manage clinically [19]. Early clini-
cal and molecular diagnosis of these familial disorders may lead to timely correc-
tion of the metabolic defect. While medical management, aimed at controlling
serum calcium and phosphate, undoubtedly has a positive effect on skeletal devel-
opment, there is also evidence that the associated dental defects may be partially or
totally rescued [20].
Cystic Fibrosis
Cystic fibrosis (CF) is a chronic respiratory disease with associated gastrointes-

tinal disease, exocrine pancreatic insufficiency and delayed growth. It is caused
by mutations in the cystic fibrosis transmembrane regulator protein (CFTR).
Skeletal and dental developmental delays are known comorbidities in CF and
the incidence of hypoplastic enamel defects has been reported to be higher than
Fig. 4.5 Show the relatively

normal macroscopic
appearance of the primary
dentition of a child with
X-linked hypophosphatemic
rickets. Note the abscess
associated with the non-
carious upper left second
primary molar
in the normal population [21, 22]. Currently the exact mechanism behind the
occurrence of DDE in CF is unknown, and as such these defects may simply
represent those expected in any debilitating illness of early childhood. However
CFTR is known to regulate the carbonic acid buffer system, controlling the pH
critical for ameloblast function and apatite deposition [23] and therefore it is
possible that there is some direct genetic impact on enamel formation yet to be
identified.
Tuberous Sclerosis (TS)
TS is a genetic disorder that can affect multiple organ systems with benign hamar-
tomas. It is considered a common epilepsy syndrome and may be associated with
autism spectrum disorder and other neurocognitive disabilities. It has long been
recognized that enamel pits (hypoplasia) are a variable feature of TS. These pits
may be widespread, mimicking some pitted forms of amelogenesis imperfecta
(AI), or sparse with fewer than 10 pits in an entire dentition (Fig. 4.6). There is
Fig. 4.6 Tuberous sclerosis,

showing enamel pits, some
made more visible by
chromogenic bacterial stain
debate as to whether the presence of enamel pits in first-degree relatives of indi-

viduals with TS is a sign of asymptomatic carrier status. Screening for the presence
of enamel pits in TS relatives is not however yet considered a reliable method of
diagnosis [24].
Other Syndromes with Enamel Defects
The Online Mendelian Inheritance in Man (OMIM) database is a catalogue of sev-

eral thousand human malformation syndromes [25]. A search for “enamel defects”
among these generates a considerable number of positive results. Many of these
syndromes are extremely rare. Reports of dental manifestations associated with
these syndromes are even more uncommon and potentially unreliable as the dental
phenotype is rarely reported by a dentist. One example of a syndrome reportedly
associated with DDE is Usher syndrome in which hypoplastic enamel has been
described in a very small number of cases [26]. However it is important to treat with
circumspection reports of enamel defects being associated with specific rare syn-
dromes, unless the numbers are sufficient to support a true association. Furthermore
in syndromes where systemic illness or failure to thrive are features of early child-
hood, the enamel defects may be secondary to the illness and any association with
the syndrome itself may be spurious.
The increased reported incidence of enamel defects in 22q11.2 deletion syn-
drome (velocardiofacial syndrome) is a good example of a positive association hav-
ing being demonstrated in a large cohort study including a comprehensive dental
examination [27]. Although affected children can variously demonstrate hypocalce-
mia and/or hypoparathyroidism, congenital cardiac anomalies and premature birth,
this study found the presence of enamel hypoplasia and hypomineralization defects
to be independent of the primary disorder.
Syndromes with Direct Genetic Effect on Ameloblasts
There are very few truly syndromic AI conditions and equally few monogenic dis-
orders with proven influence on amelogenesis. Those listed below are far from an
exhaustive list, but it is likely that many syndromes reported to express enamel
defects as part of the phenotype will in time reveal an expanded family of genes
directly involved in amelogenesis.
Tricho-Dento-Osseous Syndrome (TDO)
TDO manifests as kinky hair shafts, thin hypoplastic enamel, and increased thick-
ness of cranial bones. Abscess formation is common due to the morphology of the
taurodontic pulp chambers and extended pulp horns combined with rapid attrition
of the enamel (Fig. 4.7). The responsible gene for TDO has been identified as
DLX3, a homeobox gene expressed in all three affected tissues. A causative expla-
nation of the pathogenesis of the hypoplastic enamel defect appears in a report by
Nieminen and coworkers [28] explaining how the DLX3 expression pattern fits
with the finding that the principal dental tissue affected in TDO is the epithelially
derived enamel.
RAS/MAPK Pathway Syndromes (Noonan, Costello, LEOPARD,

and Cardio-Facio-Cutaneous Syndromes)
Recently it has been established that abnormal RAS signaling does actually have
a negative effect on enamel formation in animal and human subjects with Costello
syndrome [29]. Disorders with mutations in the molecules of the combined
RAS/MAPK pathways lead to a number of other recognizable malformation
Fig. 4.7 Tricho-dento-

osseous syndrome, showing
thin hypoplastic enamel
defects with some mild
discoloration. Tooth
sensitivity has resulted in
extremely poor oral hygiene
syndromes, notably Noonan, LEOPARD, and cardio-facio-cutaneous syndromes.

While hypoplastic enamel defects in these related conditions may be secondary
to their associated syndromic cardiac anomalies, it may, in future, be possible to
establish a direct developmental cause.
Enamel-Renal Syndrome/Enamel-Renal-Gingival Syndrome
Hunter and others reported nephrocalcinosis associated with AI and postulated that
a clinical presentation of AI should prompt referral for renal ultrasound [30].
Subsequent similar reports were termed enamel-renal syndrome and it is now
accepted that a small cohort of patients with hypoplastic, hypomineralized AI with
multiple unerupted teeth may develop nephrocalcinosis. Furthermore, a clinically
related group of AI patients with gingival fibromatosis have been found to have
causative mutations in the FAM20A gene [31] (see Chap. 5).
Epidermolysis Bullosa (EB)
These conditions are characterized by severe fragility and blistering of the skin follow-
ing minimal lateral pressure or trauma. Clinical types of EB are described by the level of
tissue separation within the epidermis (EB simplex), basement membrane (junctional
EB) and underlying connective tissue (dystrophic EB). The latter types, junctional and
dystrophic EB, are associated with enamel defects ranging from thin hypoplasia through
to widespread pitting or furrowing (Fig. 4.8a, b). A higher incidence of caries is noted in
these groups [32] though this is also likely to be linked to the difficulties in maintaining
oral hygiene when the oral mucosa is prone to blistering (Fig. 4.8c).
Autosomal Recessive Cone-Rod Dystrophy and Amelogenesis

Imperfecta (Jalili Syndrome)
This is an extremely rare autosomal recessive form of severe hypomineralization AI

in combination with reduced visual acuity, color vision abnormalities, photophobia
and visual field loss. The causative gene has been identified as CNNM4, a gene
involved in metal transportation. Interestingly, the clinical and radiographic appear-
ances of the enamel are similar to those seen in AI resulting from mutations in a
matrix metallopeptidase gene MMP20. Specialized metal transport is necessary in
the phototransduction cascade in the retina, where CNNM4 is also shown to play a
role [33]. This monogenic condition demonstrates how mutations in a single gene
expressed in development or regulation of different tissues can cause explainable
dysplasia or dysfunction in each.
Fig. 4.8 (a) Localized thin

a
enamel hypoplasia of the
primary incisors in a child
with junctional EB. (b) A
primary molar from a child
with EB showing characteris-
tic pitted enamel and bizarre
cusp morphology. (c) The
characteristic intraoral bullae
seen in a child with junctional
EB which can hamper
effective oral hygiene
c
Summary
Severe illness in early childhood can have an adverse effect on enamel formation.
Where genetic conditions feature enamel defects, they can either be directly attribut-
able to gene expression patterns during amelogenesis or the result of the impact of
systemic disease on ameloblast function. Very few conditions have been investigated in
sufficient detail to precisely determine the pathogenesis of the enamel defect. In the
future, modern in situ molecular technology should be able to demonstrate functional
pathology of disease-causing gene products during odontogenesis, at least in an animal
model of any given condition. Having said this, the mechanisms underpinning many
dental anomalies remain mysterious even in some relatively common genetic or chro-
mosomal anomalies such as trisomy 21, where anomalies of tooth number (hypodontia
and hyperdontia) and microdontia are common. Although it may seem an obscure aca-
demic exercise to be aware of these rare conditions, there are occasions when accurate
description of an enamel defect is an important step in diagnosing a rare disorder.
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Amelogenesis Imperfecta: Current
Understanding of Genotype-Phenotype 5
John Timothy Wright
Abstract
There are nearly 100 hereditary conditions that affect enamel formation.
Hereditary enamel conditions not associated with other tissue or developmental
defects are traditionally referred to as amelogenesis imperfecta (AI). Enamel
malformations involve either a deficiency in the amount of enamel (hypoplasia),
a decrease in the mineral content or change in the composition of enamel (hypo-
mineralization), or a combination of these two manifestations. The different
amelogenesis imperfectas are challenging to diagnose and treat as they are
extremely diverse in their clinical presentation and are genetically heteroge-
neous. There are multiple genes now known to cause AI and these different genes
code for proteins that are critical for normal enamel formation. Ten genes with
mutations known to cause AI have already been discovered, and the powerful
new molecular technologies now available will help identify new genes that are
associated with enamel defects. Understanding the etiology of hereditary condi-
tions affecting enamel and how the enamel differs from normal (amount and/or
composition) will allow clinicians to better advise their patients and select opti-
mal treatment approaches.
Introduction
Enamel formation involves many diverse processes that are highly controlled at the
molecular level. These processes and developmental pathways can be sensitive to
environmental conditions that can disrupt the complex processes critical for nor-
mal biomineralization [1]. There are nearly 100 hereditary conditions that affect
enamel formation that are recorded in the Online Mendelian Inheritance in Man
J.T. Wright, DDS, MS

Department of Pediatric Dentistry, University of North Carolina,
CB#7450 Brauer Hall, School of Dentistry, Chapel Hill, NC 27599-7450, USA

60 J.T. Wright
database [2]. Most of these hereditary enamel defects are associated with syn-
dromes where tissues other than enamel also are affected. Hereditary enamel con-
ditions not associated with other tissue or developmental defects are traditionally
referred to as amelogenesis imperfecta (AI) [3]. These hereditary conditions pre-
dominantly affect the quantity and/or quality of enamel in the absence of other
developmental traits [4]. The different amelogenesis imperfectas are challenging to
diagnose and treat as they are extremely diverse in their clinical presentation and
are genetically heterogeneous. Prior to the identification of any genes known to
cause AI, several studies described the prevalence and phenotype (clinical appear-
ance) of AI [5–8] in a variety of populations around the world. Studies conducted
in the United States, Israel [9, 10] and Scandinavian countries [9–13] indicate the
prevalence of AI to range from about 1:700 to 1:14,000. It is likely that most gen-
eral populations will have a prevalence of around 1:6,000–8,000 with the preva-
lence of specific subtypes varying in different populations. The purpose of this
chapter is to provide clinicians with a guide that will help them identify the differ-
ent AI types, the different causes of these conditions and how the specific genetic
cause can be related to a specific clinical appearance or phenotype. How this
knowledge is important for identifying a diagnosis and then for selecting different
treatment approaches will also be addressed.
Classification of Amelogenesis Imperfecta
Since the first descriptions of hereditary enamel defects, a variety of nomenclatures

and nosologies have been used for classifying the different AI types [14]. The vari-
ous hereditary enamel defects were given descriptive names (e.g. hypoplastic, hypo-
calcified, yellow brown, etc.) depending on their clinical and histological features.
Carl Witkop Jr. developed a classification system recognizing four main AI types
that considered the phenotype, perceived pathogenesis and mode of inheritance:
hypoplastic, hypomaturation, hypocalcified and hypomaturation-hypoplastic with
taurodontism [4]. These main groups were then subdivided into 14 subtypes based
on more distinctive clinical features and the Mendelian mode of inheritance. When
this classification system was developed none of the genes causing these conditions
were known, and it would indeed be nearly a quarter century before the first paper
on an AI gene was published. Part of the Witkop classification was based on what
he perceived was the underlying developmental mechanism or pathogenesis that
would lead to the clinical phenotype [6]. Hypoplastic AI was considered a distur-
bance in ameloblasts where these enamel-forming cells did not generate enamel
matrix adequately leading to a deficiency in amount or thickness of enamel.
Hypomaturation AI was thought to be a defect in the specific stage of enamel devel-
opment when proteinases were actively processing the remaining enamel matrix
and final enamel crystallite growth occurred (maturation stage). The hypocalcified
AI group was thought to be a defect in the biomineralization process of the enamel
mineral that continued from initiation of mineralization through development of the
entire enamel thickness. The enamel thickness in the hypomaturation and hypocal-
cified AI types was thought to be essentially normal as the ameloblasts were
5 Amelogenesis Imperfecta: Current Understanding of Genotype-Phenotype 61
secreting the enamel matrix over the full thickness of the enamel, but the mineral-
ization of the enamel was perturbed through these different mechanisms. Some AI
cases were observed to have hypoplasia and hypomineralization of the enamel as
well as taurodontism or apical displacement of the furcation in molar teeth [15].
Many of these cases were found to actually represent families with the tricho-dento-
osseous syndrome [16].
As the molecular basis of the AI conditions have been elucidated and the pheno-
types more carefully characterized using a variety of techniques, numerous investi-
gators have called for a new nomenclature that includes the molecular basis of these
conditions [17–19]. Indeed it became clear early on that there was a need to have a
consistent nomenclature to describe the many different genetic mutations occurring
in the same gene (allelic mutations) [20]. Standardized nomenclature has been
adopted for classifying mutations for AI and other conditions and there have been
some suggested changes in the AI classification but there is not at this time a clas-
sification system for AI that includes all the current genetic information [21]. Many
clinicians still use the Witkop classification and it remains, for the most part, a use-
ful way to communicate the phenotype and likely mode of inheritance. Several
modifications to the Witkop classification have been proposed (Table 5.1) based on
our increasing understanding of the pathogenesis of these conditions and these
modifications attempt to simplify some of the subtypes that were based primarily on
descriptive phenotypes (e.g., rough, smooth) [4, 22].
Inheritance of Amelogenesis Imperfecta
The early reports of enamel defects identified that they could be inherited by all the
known modes of Mendelian inheritance: autosomal dominant, autosomal recessive
and X-linked recessive [9]. The prevalence of the different subtypes varies with auto-
somal recessive AI types appearing to have a higher prevalence compared with the
autosomal dominant AI types in Middle Eastern countries [10]. The presence of a
family history of an enamel defect is very helpful in diagnosing whether the condi-
tion is indeed AI and what the AI subtype might be. Clinicians should ask patients
and parents if anyone in the family has a similar enamel defect. If so, which family
members and was there male-to-male transmission suggesting autosomal dominant
inheritance. Were males and females similarly affected or did females often show a
decreased level of severity? In the case of autosomal inherited traits, males and
females will typically be similarly affected. However, if the trait is X-linked, males
will typically have more severe manifestations compared with females due to
lyonization [23]. Female cells only express one of their X chromosomes in any given
cell so they will present a mosaic profile of affected and unaffected cells when they
carry a mutation on a gene that resides on their X chromosome. Thus, enamel in
females can be mildly or severely affected depending on the number of ameloblasts
expressing DNA from the X chromosome with or without the mutant gene. This
phenomenon of lyonization is clearly seen in the different X-linked AI subtypes
where female enamel may be only mildly hypoplastic or variable in color changes
that can present as streaks down the enamel of the tooth crown (Fig. 5.1) [24].
62
Table 5.1 Nomenclature and genetic basis for AI

Witkop classification Modified classification OMIM # Gene
TYPE I hypoplastic
IA – hypoplastic pitted (AD) AD generalized hypoplastic ? LAMB3
IB – hypoplastic local (AD) AD generalized hypoplastic 104500 ENAM
IC – hypoplastic local (AR) AR local hypoplastic 204650 ENAM
ID – hypoplastic smooth (AD) AD generalized thin hypoplastic ? ?
IE – hypoplastic smooth (X linked) X-linked generalized thin hypoplastic 301200 AMELX
IG – enamel agenesis (AR) AR generalized thin hypoplastic 614253 FAM20A
(enamel-renal syndrome) 204690
TYPE II hypomaturation
IIA – pigmented hypomaturation (AR) AR pigmented hypomaturation (IIA1) 204700 MMP20
(IIA2) 612529 KLK4
(IIA3) 613211 WDR72
(IIA4) 614832 C4ORF
IIB – hypomaturation (X linked) X-linked hypomaturation 301200 AMELX
IIC – snowcapped (X linked) X-linked snowcapped 301200 AMELX
TYPE III hypocalcified
IIIA – hypocalcified (AD) AD hypocalcified 130900 FAM83H
IIIB – hypocalcified (AR) AR hypocalcified Not listed SLC24A4
TYPE IV hypomaturation-hypoplastic with taurodontism
IVA – hypomaturation-hypoplastic with (AD) Tricho-dento-osseous syndrome AI 104530 DLX3
taurodontism (AD) TDO 190320
IVB – hypomaturation-hypoplastic with taurodontism (AR) ? ? ?
J.T. Wright
Fig. 5.1 All mutations in the

AMELX gene that cause
premature stop codons and
loss of the C-terminus of the
protein cause hypoplastic
enamel. Females with these
mutations will have variable
areas of thick and thin enamel
as seen in this affected
female’s permanent dentition
The clinical phenotypes seen with the different genetic mutations are markedly
different. These phenotypic variations occur for several different reasons. There are
multiple genes now known to cause AI and these different genes code for proteins
that have diverse functions. Thus, it is not surprising that mutations in the amelo-
genin gene that codes for the most abundant enamel matrix protein (amelogenin)
would be associated with a very different phenotype compared with mutations in a
gene coding for a proteinase like MMP20 that is involved in processing the enamel
matrix proteins. There are now over 10 different genes coding for different AI types
as reviewed in Table 5.1 [19, 25–27]. These genes code for proteins that are part of
the extracellular matrix, proteinases that process the matrix, proteins involved in
cellular attachments, proteins involved in ion regulation, genes that regulate the
expression of other genes and genes whose protein functions remain unknown at
this time (Table 5.2).
Hypoplastic Amelogenesis Imperfecta
The primary feature of the different types of hypoplastic AI is some degree of thin-
ning of the enamel. The currently known genes associated with this phenotype
include AMELX, ENAM, LAMB3, and FAM20A. Currently all the AMELX muta-
tions causing loss of protein due to signal peptide changes or loss of the C-terminus
of the amelogenin protein result in a generalized thinning of the enamel layer in
males and variable thinning in females (Fig. 5.1). Females with these types of
AMELX mutations will have vertical furrows and grooves affecting the enamel
thickness [20]. The difference in phenotype between males and females with
X-linked AI is due to lyonization as described previously.
Many of the families identified as having autosomal recessive generalized hypo-
plastic amelogenesis imperfecta (OMIM #614253 AI and gingival fibromatosis syn-
drome) and mutations in the FAM20A gene have been shown to have
microcalcifications in their kidneys and thus have enamel-renal syndrome
(OMIM#204690) [28–30]. This condition has been reported using a variety of
64 J.T. Wright
Table 5.2 Amelogenesis imperfecta genes and function

Gene Protein Functiona
AMELX Amelogenin Most abundant enamel matrix protein (90 %)
important in enamel structure formation
ENAM Enamelin Enamel matrix protein important in crystallite
elongation
WDR72 WD repeat domain 72 Intracellular protein may involve vesicle
turnover
FAM83H Family with sequence Intracellular protein may involve keratin
similarity 83, member H interaction
MMP20 Matrix metalproteinase 20 Removal of enamel matrix during secretory
stage
KLK4 Kalikrien 4 Removal of enamel matrix during maturation
stage
C4ORF26 Chromosome 4 open Extracellular phosphoprotein with capacity to
reading frame 26 promote nucleation of mineral
DLX3 Distal-less 3 protein Transcription factor
LAMB3 Laminin 5 beta chain Cell attachment
SLC24A4 Solute carrier family 24 group4 Calcium transporter
a
The specific function or functions of the different AI-associated genes and the proteins they pro-
duce are not well understood, and most of the purported protein functions listed remain to be
confirmed and fully elucidated
names with the typical oral phenotype including generalized thin hypoplastic
enamel, failure of eruption of teeth and gingival enlargement (Fig. 5.2a, b).
Management of the dentition can be very difficult due to the combination of these
features and the rather common occurrence of resorption of the unerupted teeth.
Mutations in the ENAM gene are associated with two distinct phenotypes.
Mutations that cause a loss of protein are thought to result in a localized pitted pheno-
type due to haploinsufficiency (only a single functional copy of a gene) where a
greatly diminished amount of protein is produced by the ameloblasts because only
one of the two allelic ENAM genes produces a functional protein [31, 32]. This phe-
notype (OMIM#104500) is inherited as an autosomal dominant trait and is character-
ized by horizontal pitting or grooves that decorate the clinical crown. These hypoplastic
pitted/grooved areas are juxtaposed between areas of enamel that are full thickness.
The enamel color appears normal indicating a normal mineral content. Other ENAM
mutations produce a generalized thin hypoplastic phenotype (OMIM#104500)
through a dominant negative mechanism where it is thought that some dysfunctional
protein is produced that interferes with the normal process causing a more global
amelogenesis dysfunction and thin enamel over the entire dental crown. There are a
few case reports of hypoplastic AI due to ENAM mutations being inherited through
an autosomal recessive manner (OMIM#204650) [33].
Some presentations of AI have been shown to be associated with mutations that
have effects in other tissues. Hypoplastic AI has recently been associated with
mutations in genes that are important in cell-to-cell attachments such as LAMB3
[27]. The protein product from the LAMB3 gene and two other genes form the pro-
tein laminin 5 that is critical for anchoring the epidermis and dermis. Some
Fig. 5.2 (a) AR generalized

a
thin hypoplastic AI with a
failure of some teeth to erupt
as seen in this 10-year-old
females panoramic radio-
graph result from FAM20A
mutations. (b) Clinically the
teeth were small and spaced
due to the very thin enamel,
and the gingiva was fibrotic
and overgrown in the
maxillary anterior region.
This affected individual also
had multiple small calcifica-
tions in her kidneys
consistent with the diagnosis
b
of enamel-renal syndrome
mutations in this gene are associated with junctional epidermolysis bullosa (OMIM#
226700, 226650) that is associated with tissue fragility and a propensity to develop
large blisters and a hypoplastic pitted to generalized thin enamel phenotype [34].
Recently families with no predilection or history of blistering or skin manifestations
have been identified to have LAMB3 gene mutations associated with a hypoplastic
enamel phenotype. It is likely that other genes important in cell-cell or cell-matrix
interactions or other ameloblast critical functions will be found to be associated
with hypoplastic enamel defects in the future. The majority of enamel defects
reported with syndromes are of the hypoplastic phenotype although many of these
conditions have not been fully characterized to determine if hypomineralization
also is a phenotypic component.
Hypomaturation Amelogenesis Imperfecta
Hypomaturation AI phenotypes are associated with multiple genes that impact

on the maturational process of amelogenesis (i.e. protein processing to allow
crystallite mineralization and growth). Five genes are currently associated with
this classification and phenotype (AMELX, MMP20, KLK4, WDR72, C4ORF26)
66 J.T. Wright
Fig. 5.3 The permanent dentition of males with the P70T mutation in the gene that codes for
amelogenin have X-linked hypomaturation AI have a relatively normal enamel thickness with the
coronol two thirds of the crown having a brown discoloration and the cervical area being white
opaque in color. The primary molars all have a white opaque coloration
[19, 25, 35]. Mutations in the first three of these genes are known to involve pro-
cessing of the enamel matrix. The role of WDR72 is not clear and the C4ORF26
protein may be important in regulation of crystallite mineralization. The clinical
phenotype that results from all of these mutations includes enamel that is typically
of normal thickness but is hypomineralized, has an increased protein content com-
pared with normal fully mineralized enamel and as a result is abnormal in color
and appearance [19]. Inheritance is either X-linked or autosomal recessive depend-
ing on the gene involved.
X-linked hypomaturation AI results from AMELX mutations that cause the ame-
logenin protein to be processed abnormally and at a slower rate [36]. For example,
the AMELX P70T mutation causes a change of the proline amino acid at position 70
to a tyrosine and this alters a major proteinase cleavage site for MMP20, the pri-
mary proteinase for processing the amelogenin protein. In affected males, this
results in enamel that in the primary dentition has a white opaque coloration and a
brown coloration with a white opaque cervical enamel in the permanent dentition
(Fig. 5.3) [37]. Females will have vertical striping of this discoloration due to
lyonization [23].
The proteinases primarily responsible for processing the enamel matrix proteins
(e.g. amelogenin, enamelin, ameloblastin, amelotin, etc.) are MMP20 and KLK4
[38]. Although MMP20 (a matrix metalloproteinase) is primarily active during the
secretory stage of development, it is associated with hypomaturation AI due to its
role in matrix processing that is a requisite for normal mineralization. KLK4 on the
other hand is active in the maturation stage and is an aggressive serine proteinase
that cleaves a variety of proteins to help ensure as much enamel matrix is processed
and removed as possible to allow the enamel crystallites to grow and mineralize to
the fullest extent. Enamel is normally about 85 % mineral per volume or 95 % by
Fig. 5.4 (a) All autosomal

a
recessive hypomaturation AI
types reported to date have a
brown to orange coloration
and enamel that is develop-
mentally of normal thickness
but that often fractures from
the teeth as they erupt due to
the enamel’s reduced mineral
content. (b) The panoramic
radiograph of this female that
has a WDR72 mutation
shows the unerupted teeth
have a normal outline of the
crown, but there is little
contrast between enamel and
dentin due to their similar
mineral content. The primary
molars and maxillary incisors b
show marked enamel loss,
while the first permanent
molars also are beginning to
show enamel fracturing
weight [39]. All of the hypomaturation AI types that have been characterized bio-
chemically have retention of protein and decreased mineral content [40].
Interestingly, the mineral content varies substantially between the different hypo-
maturation AI types with the X-linked form having a higher mineral content than
the proteinase-associated AI types, while the C4ORF26-associated AI has a very
low mineral content and very high protein content [19, 24, 41]. Typically, the higher
the protein content, the lower the mineral content and the more likely the affected
individual is to have hypersensitivity of the teeth to thermal and chemical stimuli
and loss of enamel as the teeth come into function.
The degree of enamel mineralization can be assessed clinically by features such
as coloration of the dentition (discoloration is associated with decreased mineral
content and increased protein content), enamel loss and fracturing and lack of radio-
graphic contrast between enamel and dentin on radiographs (Fig. 5.4a, b). The pres-
ence and appearance of these phenotypic features can be helpful in determining
which AI type an individual has as well as what the appropriate treatment might be.
Enamel that is discolored, poorly mineralized, suffers fracturing from the crown and
is associated with hypersensitivity displays phenotypic features that should lead the
clinician to consider some type of full coronal coverage treatment.
68 J.T. Wright
Fig. 5.5 (a) Individuals with

a
autosomal dominant
hypocalcified AI typically
have a markedly reduced
mineral content and
generalized yellow brown
discoloration that affects all
the teeth similarly as seen in
the incisors of this child that
has a FAM83H mutation. The
teeth are frequently
hypersensitive and it is
common to have marked
gingival irritation and heavy
calculus formation. (b)
Radiographically this b
10-year-old child’s enamel
has been lost from all of the
first permanent molars except
around the cervical area.
There is little contrast
between enamel and dentin,
and the unerupted crowns
have a normal morphology
Hypocalcified Amelogenesis Imperfecta
The primary feature of hypocalcified AI is the marked reduction in the mineral con-
tent of the enamel that can be similar or even less than that of normal dentin. Most
cases of hypocalcified AI are inherited as an autosomal dominant trait and are
caused by mutations in the FAM83H gene. Typically all of the teeth in both the pri-
mary and permanent dentitions are similarly affected. The lack of mineral and
increased protein content diminishes the insulating properties of the enamel and
hypersensitivity is often a feature of this AI type. Affected individuals frequently
have marked gingival inflammation and can have extensive calculus formation
(Fig. 5.5a). The incompletely mineralized enamel contrasts poorly with the dentin
on radiographs and tends to break away from the teeth as they come into function
shortly after emergence into the oral cavity (Fig. 5.5b).
Some families have FAM83H mutations that are located farther in the 3-prime
direction resulting in a genetic code that would generate a protein that is not as
truncated as those produced by most FAM83H mutations. This slightly less trun-
cated protein may have some functionality resulting in affected individuals having
a localized hypocalcified phenotype with the cervical area of enamel typically being
affected, while the rest of the dental crown is relatively normal. This is a relatively
uncommon phenotype as most cases of hypocalcified AI involve the entire dental
crown. There also can be autosomal recessive hypocalcified AI cause by mutations
in the SLC24A4 gene although these cases appear to be rare as well.
Hypomaturation/Hypoplastic Amelogenesis
with Taurodontism
Taurodontism or elongation of the pulp chamber due to apical displacement of the

floor of the pulp chamber and root furcation appears to occur with the different AI
types with a prevalence similar to that in the general population [42]. Many of the
cases reported in the literature as “AI with taurodontism” have later been recognized
to be the autosomal dominant trait tricho-dento-osseous syndrome (TDO) that is
caused by a mutation in the DLX3 gene [42–44]. This gene regulates the expression
of other genes and is involved in hair, tooth, and bone formation which are the three
primarily affected tissues of the TDO syndrome. Two families with a different
mutation in the DLX3 gene do not display a bone phenotype and have a less severe,
but noticeable, course hair phenotype [45, 46]. As increasing phenotypic variability
is discovered from mutations in the same gene, it becomes evermore challenging to
determine how best to classify and name these conditions.
Malocclusion and Amelogenesis Imperfecta
The presence of class III malocclusion with or without a skeletal open bite is much
more prevalent in individuals with AI than the general population. Studies indicate
around 25–45 % of individuals with AI will have these types of malocclusions [47,
48]. This phenotypic feature can occur in any of the AI types and is not always
associated with self-reported dental hypersensitivity. It has been proposed that this
could represent a direct effect of the mutated gene or may be a secondary effect. It
seems likely that most of the open bite and class III malocclusions are not due
directly to the dysfunctional mutant protein but due to other factors that remain
unclear such as changes in bite force and tone of the muscles of mastication. These
malocclusions certainly add greatly to the complexity, expense and duration of
management of some AI cases.
Future Directions and Amelogenesis Imperfecta
The diagnosis of AI and its molecular causes at the gene level have advanced greatly
since the first genetic mutation was identified in the amelogenin gene in 1991. New
molecular techniques such as whole-genome sequencing make it possible to iden-
tify causative mutations with only a few affected individuals. Consequently, there
are now 10 plus genes with mutations known to cause AI and there is no doubt that
these powerful molecular technologies will help identify new genes that are associ-
ated with enamel defects. Knowing the molecular basis of the different AI types
allows affected individuals and their families to have a definitive diagnosis that in
the past was extremely challenging to obtain given the many types of AI and the
diverse syndromic conditions that affect enamel formation. Clinicians that know the
AI type and how the enamel is affected will be better able to identify treatment
strategies and select the materials that are likely to generate optimal outcomes.
70 J.T. Wright
Understanding whether one should restore using bonding approaches or full-

coverage restorations is often predicated on understanding how well or poorly the
enamel is mineralized. It seems unlikely that there will be direct therapeutics related
to our molecular understanding of the AI etiologies in the short term; however, this
is occurring with other conditions and could be a possibility in the future.
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Molar Incisor Hypomineralization:
Structure, Composition, and Properties 6
Erin K. Mahoney and Rami Farah
Abstract
The first permanent molars in molar incisor hypomineralization (MIH) are
characterized by localized demarcated lesions or opacities within the enamel.
These lesions are often rough and plaque retentive and at risk of rapid caries
and post-eruptive breakdown (PEB). There is increasing evidence to suggest
that the physical, chemical and mechanical properties of MIH-affected enamel
are different to those of otherwise healthy enamel. Studies suggest that the
hardness and modulus of elasticity of MIH-affected enamel are reduced by
between 50 and 75 % and are accompanied by a simultaneous 20 % reduction
in mineral content. Furthermore, the protein content of affected enamel is up to
15 times higher than in sound enamel particularly in the darker brown opaci-
ties. These findings may explain why hypomineralized enamel fractures easily
under occlusal function causing PEB. Scanning and transmission electron
microscopic studies have shown that the microstructure of this enamel is more
disorganized and, when etched with phosphoric acid, it does not show the typi-
cal etching pattern. This may contribute clinically to the compromised bonding
of adhesive dental materials to affected teeth. Knowledge of the physical and
mechanical properties and composition of developmentally defective enamel
helps clinicians understand the challenges associated with treating affected
individuals.
E.K. Mahoney, BDS, MDSc PhD (*)

Department of Dentistry, Hutt Valley District Health Board,
84 Te Anau Road, Hataitai, Wellington 6021, New Zealand
R. Farah, BDS, MPhil, DClinDent, PhD
Department of Oral Sciences, University of Otago,
310 Great King Street, Dunedin 9016, New Zealand

74 E.K. Mahoney and R. Farah
Introduction
The first permanent molars in children with MIH are characterized by localized demar-
cated hypomineralized enamel lesions or opacities with compromised mechanical
properties. These hypomineralized lesions are often rough and plaque retentive which,
coupled with hypersensitivity, makes adequate oral hygiene difficult. The net result is
a predisposition to rapid caries and post-eruptive breakdown (Fig. 6.1). Over the past
15 years, there has been a growing body of research focused on understanding the
physical and chemical properties and the behavior of such hypomineralized lesions.
This is important as it helps clinicians to make informed treatment choices and pro-
vides greater insight into the likely long-term prognosis of these compromised teeth.
This chapter summarizes what is known about the structure, composition and
properties of hypomineralized enamel and relates this knowledge to the clinical
appearance and behavior of MIH-affected teeth. The first part of this chapter briefly
reviews otherwise healthy sound enamel, while the second part describes the macro-
and microscopic appearance of MIH enamel, its chemical and structural properties
and their impact on its mechanical behavior.
Sound Enamel
Fully formed, sound enamel is 96 % weight and 86 % volume mineral (inorganic).

It is produced by ameloblasts, which are highly specialized calcium transporting
cells that are lost once amelogenesis is complete and the tooth erupts. Enamel is
unique in the body, as it does not have the ability to heal or regenerate once tooth
eruption is complete. The resulting enamel in health is a well-organized, highly
mineralized, hard tissue that can withstand significant occlusal forces and the chal-
lenging oral environment.
Enamel mineral is initially a carbonated apatite which, through a process of
maturation, is ultimately composed predominately of hydroxyapatite crystals
(Ca10(PO4)6(OH)2) with trace elements such as magnesium, fluoride, strontium and
lead. Although highly mineralized enamel does allow some movement of molecules,
Fig. 6.1 An upper first

permanent molar affected by
MIH showing characteristic
predisposition to post-
eruptive breakdown
superimposed with dental
caries
6 Molar Incisor Hypomineralization: Structure, Composition, and Properties 75
in comparison to dentine its permeability in health is minimal. The orientation of

the crystals together forms the rod structure (prism), which represents the “mineral-
ized trail” taken by the ameloblasts and their Tomes processes as they migrate along
an undulating course from the amelodentinal junction (ADJ) to the enamel surface.
Enamel rods are between 3 and 7 μm in diameter. There are approximately 1,000
crystals found in each rod and each rod interdigitates with the neighboring ones.
Where the rods meet, the crystals have different directions to this in the neighboring
rods, thus creating a very narrow interface with slightly increased space between
the crystals containing a greater abundance of organic matter. This area between the
different rods is known as inter-rod areas or rod sheaths (Fig. 6.2).
Enamel does contain some organic material but only 1 % by weight (2 % by
volume) and with a further 4 % water by weight (12 % by volume). The organic
component of enamel is composed of proteins and lipids, which are produced
mainly by the ameloblasts, although some may be derived from exogenous sub-
stances such as blood and serum. An area of higher concentration of organic mate-
rial is found in the “tuft” region. Enamel tufts lie along with lamellae and spindles
and are normal defects found in mature enamel but may represent an area of
mechanical weakness. The role of the protein in enamel is still unclear but is thought
to affect the behavior of this complex tissue, reducing its brittleness and imparting
it with more metallic-like mechanical properties [1].
Hypomineralized Enamel
Macroscopic Changes
Clinically, MIH enamel defects appear as well-demarcated opacities within other-

wise normal-looking enamel. These opacities are generally visible to the naked eye
and vary in color from creamy-white to yellow or brown and affect the cuspal areas,
Fig. 6.2 Basic organization

of the enamel rods as seen
under the SEM. (a) Typical
rod structure. (b) Inter-rod
area (rod sheath)
Fig. 6.3 A section through

an extracted MIH-affected
first permanent molar
showing the lesion extending
from the ADJ outwards
through the occlusal surface
with apparently unaffected
cervical enamel
inclined planes and smooth surfaces. When MIH teeth, with clinically obvious
opacities, are extracted and sectioned prior to any in vitro testing, the lesion usually
extends from the ADJ to the surface of the tooth and the cervical enamel appears
normal macroscopically (Fig. 6.3).
Mechanical Properties
The term “mechanical properties” refers to the characteristics of a material that

determine how it reacts when subjected to some type of force. Understanding the
mechanical properties of hypomineralized enamel helps clinicians predict the
behavior of MIH-affected teeth. Two properties in particular, hardness and elastic
modulus, have been the focus of most research. The hardness of a material provides
a measure of its resistance to permanent indentation and is considered to reflect its
susceptibility to abrasive wear. Elastic modulus provides information on how a
material flexes under loading/pressure such as occlusal forces. Both hardness and
elastic modulus testing rely on dropping an indenter of a known size and shape into
the material under test. The size or depth of the resulting indent is measured, and the
resulting “hardness” is calculated as pressure (force/area). The elastic modulus
depends on the shape of the loading/unloading curve of the indenter and is also
measured in the units of pressure. Unfortunately, different studies use different units
such as GPa or Knoop hardness number (KHN), which makes inter-study compari-
sons difficult.
Sound enamel has a hardness of between 3.5 and 5.0 GPa while its modulus of
elasticity is 77.25 ± 3.15 GPa (see Table 6.1) [2, 3]. This confirms that sound enamel
is very hard and resistant to wear. In comparison sound dentine has a low wear
resistance, with a hardness of around 0.83 GP and is more flexible than enamel with
a modulus of elasticity of approximately 20–25 GPa [4]. Hypomineralized enamel
has been shown to have mechanical properties that are similar to those of dentine as
Table 6.1 Hardness and modulus of elasticity of hypomineralized vs sound enamel

Average hardness Average modulus of
(GPa) elasticity (GPa)
Sound enamel (control tooth) 3.66 ± 0.75 75.57 ± 9.98
Sound dentine 0.83 ± 0.13 20–25
Hypomineralized enamel 0.53 ± 0.31 14.49 ± 7.56
opposed to those of sound enamel. Hardness values for enamel from hypomineral-
ized first permanent molars have been reported as low as 0.5 GPa up to approxi-
mately 2 GPa with a modulus of elasticity of around 15 GPa [2, 3]. This 50–75 %
reduction in the mechanical properties suggests that hypomineralized enamel has a
low resistance to wear and will flex on loading which helps explain why MIH-
affected teeth appear clinically weaker and more prone to fracture. Further work by
Crombie and colleagues has shown that in general (although not always) white/
cream-colored opacities are harder than yellow-brown lesions [2]. This information
can be used clinically to help predict which teeth are likely to fracture or wear on
eruption and which may be able to be monitored over time.
The mechanical properties of sound enamel do vary across the tooth surface
[5– 7]. This has also been found in the enamel of hypomineralized first permanent
molars with the surface of the lesion being harder than the body [8]. Furthermore,
there is a transitional zone between the apparently sound enamel of the cervical
region and the hypomineralized defect (Fig. 6.4a–c). This transitional zone is
approximately 500–600 μm (0.5–0.6 mm) in width, with a linear reduction in
mechanical properties from the sound to affected enamel [9].
Studies have confirmed that the hardness and modulus of elasticity of enamel in the
cervical region are essentially normal. This means that clinicians can expect this region
to support normal bonding for restorative materials such as resin-based composites
whereas adhesion in hypomineralized regions of enamel may be compromised.
Microstructure
In an attempt to explain why the mechanical properties of hypomineralized enamel

differ so significantly from sound enamel, microstructural studies have been com-
pleted using both scanning electron microscopy (SEM) and transmission electron
microscopy (TEM). SEM uses the reflection of a beam of electrons that are scanned
across the surface of a specimen reflected to form an image. It allows detailed three-
dimensional analysis of the surface of a given specimen. TEM allows for higher
resolution by transmitting a beam of electrons through an ultrathin specimen.
Depending on the composition and thickness of the specimen, some of the electrons
are scattered and disappear and the unscattered electrons hit a fluorescent screen,
which can be photographed or visualized directly. This allows investigation to a
higher resolution than light microscopy and SEM.
HYPOMINERALISED
LAST ENAMEL
INDENT
LINE OF TRANSITION ZONE

INDENTATIONS
250 µm UNAFFECTED
PARALLEL TO ADJ ENAMEL
FIRST
INDENT
b Hardness of Control Tooth

5
4
Hardness GPa
0
0 1000 2000 3000 4000
Distance from CEJ (microns)
c Hardness of Test Tooth

6
5
Hardness (GPa)
4
3
WIDTH OF TRANSITION REGION
2
1
0
0 1000 2000 3000 4000
Distance from CEJ (microns)
Fig. 6.4 (a) A cross section through an MIH-affected first permanent molar showing the transi-
tional zone between the occlusal-affected enamel and the normal cervical enamel. (b) Hardness of
unaffected control tooth from enamel at CEJ (cementoenamel junction) to a position level with the
dentine cusp tip. (c) Hardness of first permanent molar seen in (a) showing the transitional area
found between the sound and hypomineralized enamel
Enamel
Sheath
Fig. 6.5 A TEM image of hypomineralized enamel crystals showing the increased width of the
enamel sheath structure (Courtesy of Zonghan Xie, Mark Hoffman, and Michael Swain)
The microstructure of sound enamel confirms its well-organized rod architecture

and well-defined borders with narrow inter-rod regions without defects or porosities
[10]. This also applies to the clinically normal looking, sound cervical enamel of
MIH teeth. Under SEM, the affected enamel does show some of the basic architec-
ture of the enamel rods, but there is always a varying degree of disorganization with
increased porosities [9–11]. In moderately affected areas, the boundaries between
the enamel rods are somewhat blurred, and the crystals are not tightly packed. In the
more severely affected areas, the rods are very thin with wide gaps in between con-
taining what appears to be organic material. The border between the normal cervical
enamel and the affected occlusal part is always distinct. This can give clinicians
further confidence when extending adhesive restorations onto the clinically normal-
looking cervical enamel.
TEM studies of hypomineralized enamel are difficult to do as they require very
thin samples for analysis. However, a few studies have been reported in which the
higher magnification associated with TEM has allowed visualization of individual
crystals within the enamel. TEM imaging of sound enamel shows that the apatite
crystals are well organized with elongated crystals running along the long axis of
the enamel rods. The rod sheaths are barely distinguishable and the organic material
in this region is minimal. In contrast, TEM images of hypomineralized enamel have
shown that this enamel is more porous and the crystals more loosely packed. The
rod sheaths also show increased porosity making the sheath significantly wider than
in sound enamel (see Fig. 6.5) [12]. It has been hypothesized that the wider sheath
structure and less densely packed crystals mean that the enamel rods are more easily
deformed under occlusal loading.
Restorative materials such as resin-based composites require micromechanical
retention to bond effectively to the tooth surface. Successful adhesion to enamel is
promoted by acid etching prior to placement of the resin-based material. The effect
of phosphoric acid etchant on hypomineralized enamel is therefore important. SEM
studies have consistently shown that, regardless of the etching time, exposure of
hypomineralized enamel to phosphoric acid fails to produce any of the traditional
etching patterns seen in sound enamel [13, 14]. It has been suggested that this
abnormal etching pattern may be the result of excess proteins remaining in the com-
promised enamel preventing normal acid dissolution [10].
The microshear bond strength of a resin-based composite to hypomineralized
enamel has been shown to be significantly less (up to a 54 % reduction) compared
with that to sound enamel [13]. Furthermore, SEM studies confirmed a high fre-
quency of cohesive failures within the compromised enamel as opposed to an adhe-
sive failure at the interface with the composite material. This suggests that the
hypomineralized enamel failed when stress was applied i.e. the enamel itself was
weaker than the strength of the bond between the resin and compromised enamel.
The less densely packed crystals in the rods are associated with reduced mineral
density and in turn compromised mechanical properties. Mineral density is an indi-
cation of the degree of mineralization of a given material. The higher the mineral
density, the more mineralized the tissue and the more tightly packed the crystals.
The reduced mineral density of MIH enamel has been confirmed using x-ray
microtomography [15, 16]. This technique utilizes a small version of the computer-
ized tomography (CT) scan to take multiple radiographic images of the specimen
under study from multiple angles. A computer then uses the multiple radiographs to
reconstruct a three-dimensional image of the specimen (in black and white as in
conventional radiographs). Just as in conventional radiographs, the whiter the speci-
men (or enamel in this case), the more mineralized it is, and the darker the enamel,
the less mineralized it is (hypomineralized). This is referred to as the gray-level
reading of the enamel. The gray level can be read (given a number) depending on
how white or dark it is, and this number can then be used to directly calculate the
mineral density of enamel. The mineral density of affected MIH enamel is, on aver-
age, around 20 % lower than that of sound enamel and varies across the lesion [15].
Cervically, where the enamel appears clinically normal, the mineral density is nor-
mal; however it drops across the transitional zone into the affected occlusal region.
The mineral density is lowest in the center of the lesion. Using x-ray microtomog-
raphy it was also demonstrated that the MIH defects follow the incremental lines of
enamel formation. Three dimensionally, this suggests that defects are shaped like an
irregular cone, with the narrow tip located close to the ADJ and the wider base fan-
ning out towards the enamel surface.
In addition to a reduction in the mineral density, the less densely packed crystals
are associated with a 5–25 % increase in porosity as demonstrated using polarized
light microscopy [2, 11, 17]. The high porosity in MIH enamel, combined with wide
dentinal tubules, may allow for easier irritation of the thermal and chemical stimuli
to the pulp. Rodd and co-workers demonstrated quantitative changes in the pulpal
tissue of hypomineralized teeth, with increased neuronal and vascular expression of
a noxious heat receptor in some pulpal regions [18]. This is indicative of underlying
pulpal inflammation. Clinically, this inflammation leads to heightened pulpal excit-
ability and sensitivity in the affected teeth, making a simple procedure like brushing
the teeth or drinking a cold or a warm beverage difficult for MIH-affected
individuals. This hypersensitivity can also make it difficult to achieve adequate

local anesthesia. The use of local anesthesia supplemented by sedation or systemic
pain relief can be helpful in treating affected children [19, 20].
There is a link between the color or shade of the enamel and the severity of the
defect. Clinically, the darker the enamel i.e. yellow-brown as opposed to white-
chalky, the more porous it is and the less its mineral density [17, 21]. This suggests
that the darker the enamel opacity, the more likely it is to fracture under normal
occlusal loads which has been demonstrated in one prospective cohort study [22].
Composition
Enamel is made up of two phases: an inorganic (mineral) phase of hydroxyapatite

crystals and an organic phase of mainly proteins and some lipids. The proteins are
mainly intrinsic enamel proteins such as enamelin and amelogenin.
The inorganic component of MIH enamel has been studied extensively using a
variety of methods. The conventional calcium hydroxyapatite crystals found in nor-
mal enamel is the only calcium phosphate phase present in MIH enamel [3]. The
calcium and phosphate content is lower in MIH enamel than in sound enamel [23],
but they have similar Ca/P ratios. However, MIH-affected enamel has increased
carbon content which reflects an increase in both carbonate [2] and protein content
[24]. The increase in carbonate makes the affected enamel more susceptible to den-
tal caries because carbonated crystals dissolve more easily under caries acid attack.
However, the increased protein content increases enamel resistance to acid attack,
as the proteins are more resistant to acid dissolution. As a result the association
between caries and MIH remains unclear.
As for other trace elements, there is probably a slightly higher amount of magne-
sium in MIH enamel than in sound enamel, which suggests some form of disruption
to amelogenesis. However, concentrations of chlorine, strontium, sodium, and
potassium in MIH enamel are comparable (or slightly higher) to those in sound
enamel [9, 23].
As mentioned earlier there is an inverse relationship between the clinical appear-
ance of the opacities seen in MIH and its mineral density, with darker lesions con-
taining less mineral. Conversely, there is a positive correlation between the shade
and the amount of protein contained in these lesions. Studies have shown that brown
MIH enamel has a 15–21-fold higher protein content than sound enamel. The pro-
tein content of both white/opaque and yellow enamel is approximately eight times
higher than sound enamel [21, 24]. Increases in protein content have also been
reported in the hypomineralized enamel that characterizes both hypomaturation and
hypocalcified amelogenesis imperfecta (AI) types (see Chap. 5) [25, 26]. However,
while the proteins identified in AI enamel are mainly intrinsic enamel proteins (e.g.,
amelogenins, enamelins), those found in MIH enamel are mainly serum and blood
proteins. Indeed MIH enamel has been reported to have essentially normal levels of
amelogenins [27]. The main protein found in MIH enamel is albumin with other
serum proteins, such as alpha-1-antitrypsin and antithrombin III also present.
Hemoglobin and proteins involved in tissue injury and its repair, or in bleeding and
coagulation, have also been detected, but with less abundance than serum proteins
[24, 27].
The presence of serum proteins in MIH enamel is peculiar. While minute amounts
of albumin and other serum proteins do enter enamel during development, they are
degraded and removed during the maturation phase [28]. Only trace amounts are
detected in mature sound enamel. It is unclear how such an abundance of serum
proteins (and some hemoglobin) can gain access into MIH enamel. The most likely
explanation is that there is “leakage” of serum (and perhaps blood) into MIH enamel
during its formation. If this leakage occurs during the transition and maturation
stages of amelogenesis it is likely to have a detrimental effect because albumin has
the capacity to bind to the immature apatite crystals, inhibiting their growth [29]. In
normal enamel formation, albumin degradation in the maturation stage is a prereq-
uisite for maximal crystal growth. In addition, alpha-1-antitrypsin and antithrombin
are serine proteinase inhibitors, interfering with the function of the proteinase kal-
likrein 4 (KLK4). KLK4 secreted during these stages of amelogenesis degrades the
organic matrix remaining from the secretion stage. This facilitates the continued
deposition of minerals into enamel required for full mineralization of hard enamel.
The presence of antitrypsin and antithrombin may impair KLK4 activity resulting in
hypomineralized enamel with the associated elevated protein and reduced mineral
content.
Conclusion
The structure, composition, and properties of hypomineralized enamel are fun-
damentally altered which in turn affects its behavior and response to both the oral
environment and dental treatment. Biomaterial science and scientists, through
the use of a variety of in vitro techniques, can help clinicians understand these
differences. Further research, which should also extend to hypomineralized pri-
mary enamel, is required to identify ways to optimize mineralization of develop-
mentally defective enamel and to improve both prevention and treatment
strategies in the future.
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The Psychosocial Impacts
of Developmental Enamel Defects 7
in Children and Young People
Zoe Marshman and Helen D. Rodd
Abstract
Within pediatric healthcare, increasing importance is being placed on the
patient’s own experience of illness and related treatments. Clearly there is a
need for dentists to also appreciate how various oral conditions may impact on
their young patients. The dental literature has a long tradition of epidemiologi-
cal, clinical, and laboratory research relating to developmental defects of
enamel (DDE). Psychosocial research, however, is a more recent line of
enquiry, and one that is still in its infancy, particularly where children and
young people are concerned. In this chapter we will consider how disturbances
in enamel formation can affect the appearance and function of teeth which, in
turn, can impact on an individual’s emotions and social interactions. In addi-
tion, the need for patients to undergo, sometimes complex and prolonged,
courses of treatment may bring its own positive or negative effects. We will
first broadly consider the various approaches that can be used to gain insight
into children’s perspectives of oral conditions and dental treatment. The psy-
chosocial impacts of DDE will then be described in terms of how they affect
the individual, how dental interventions affect the individual, and, lastly, how
others view young people with DDE.
Z. Marshman, BDS, MPH, DDPH, PhD (*)

Academic Unit of Dental Public Health, School of Clinical Dentistry, University of Sheffield,
Claremont Crescent, Sheffield, South Yorkshire S10 2TA, UK
H.D. Rodd, BDS (Hons), PhD
Department of Oral Health and Development, School of Clinical Dentistry,
University of Sheffield, Claremont Crescent, Sheffield, South Yorkshire S10 2TA, UK

86 Z. Marshman and H.D. Rodd
Introduction
Over the last decade, there has been growing appreciation of the relationship
between oral health status and children’s quality of life or well-being. This has led
to a wealth of studies exploring the impact of dental disease, dentoalveolar trauma,
malocclusion, and dental or craniofacial anomalies on both oral health-related and
general health-related quality of life [1–6]. Furthermore, greater emphasis is now
being placed on young patients’ perspectives and experiences of dental care and
their participation in decision-making [7]. It is speculated that changes in how chil-
dren are viewed and engaged in dentistry may underpin and facilitate future enamel
defect-related research and service evaluation.
Research into the impacts of DDE may be driven by different agendas. Firstly, at
the population level, there has been a need to establish whether DDE constitute a
public health concern in the ongoing debate about the risks/benefits of water fluori-
dation. Indeed, the majority of psychosocial DDE-related research to date has been
conducted in areas of natural or artificial water fluoridation in both developed and
developing countries. Secondly, at the patient level, clinicians need to fully under-
stand the impacts of DDE for each individual in order to better meet their needs and
treatment expectations.
The media and celebrity industry also play a key role in shaping how society
views and values appearance. Many children are growing up in a world where unre-
alistic body images are portrayed as desirable. A “perfect” smile of straight and
artificially white teeth is inherent to this globalized representation of beauty. There
is little tolerance for tooth color that deviates from the norm, placing a greater psy-
chosocial impact on the individual and presenting more complex clinical and ethical
challenges for the dentist.
Child-Centered Approaches to Research

and Service Evaluation
A variety of methods, both qualitative and quantitative, may be used to engage chil-
dren in research about their oral health and experiences of treatment [8]. Oral
health-related quality of life (OHRQoL) questionnaires have dominated quantita-
tive research in this field. The most frequently used child measures include the age-
specific Child Perceptions Questionnaires (CPQ11–14 and CPQ8–10) [9–11], the Child
Oral Health Impact Profile (Child OHIP) [12], and the Child Oral Impacts on Daily
Performances (Child OIDP) Questionnaire [13]. It should be borne in mind that
these instruments are generic OHRQoL measures, and although they have been
used with children with DDE [1, 14–16], they are not specific for enamel condi-
tions. Studies have also employed proxy (parent) assessments of child OHRQoL in
relation to DDE [2], but these will not be reviewed in this chapter as the focus is on
children’s self-reported impacts. Multidisciplinary research has also examined the
relationship between the impact of DDE and various psychological constructs such
as coping styles or self-esteem [17, 18].
7 The Psychosocial Impacts of Developmental Enamel Defects 87
In view of the recognized limitations of questionnaires in capturing the full spec-

trum of an individual’s experiences, qualitative methods have been used to gain a
more detailed insight into the impacts of DDE. Common approaches have included
interviews, focus groups, and written diaries [16, 19–22], but there is considerable
scope to utilize more diverse participatory activities such as video diaries, photo-
elicitation, creative writing, drawings, and role play.
Psychosocial Impacts of Enamel Defects on the Individual
Background
As mentioned previously, both qualitative and quantitative approaches have been

employed to determine the impacts of DDE on children, with greatest insights
gained from studies which have incorporated a mixed method approach. A key find-
ing to emerge from the literature is that there is no clear relationship between the
severity of the condition, as measured by normative data (e.g., epidemiological indi-
ces of enamel defects), and the impact of DDE from the child’s own perspective [23,
24]. This may be attributed to the complex interplay between individual character-
istics such as coping strategies and concepts of the self (e.g., self-esteem and self-
confidence) which may all modify a person’s response to having a visible difference
[20, 24–26]. One area which remains completely un-researched is whether the etiol-
ogy of the DDE, inherited or environmental, has any bearing on the reported
impacts. The prevalence of DDE in the general population has, however, been con-
sidered as a modifying factor on how children feel about their teeth. Interestingly,
there are conflicting reports as to whether children living in areas where DDE are
the “norm” (regions of endemic dental fluorosis) actually experience any less nega-
tive impacts relating to social interactions and satisfaction with their appearance
[27–29]. The following sections will review some of the key studies which have
described or measured impacts in young populations relating to a variety of DDE.
Impacts Relating to Dental Fluorosis
In the main, the psychosocial literature has focussed on children with DDE on per-
manent teeth attributed to dental fluorosis [28] and less is known about how condi-
tions such as amelogenesis imperfecta (AI), molar incisor hypomineralization
(MIH), or trauma-related sequelae affect individuals.
One of the earliest studies to consider the psychosocial impact of severe dental
fluorosis was conducted with 13- to 15-year-olds living in Tanzania [27]. The main
finding was that 70 % of respondents said that the way their teeth looked hindered
them from smiling freely. Interestingly, the negative impact of DDE on smiling has
been a common theme throughout the literature.
A more detailed investigation was later carried out in Tanzania, in an area where
75 % of the population had a Thylstrup-Fejerskov Index (TFI) score of ≥2 [14]. To
Fig. 7.1 Photograph of teeth

of a participant with
development enamel defects
who said: “I always wanted to
change my teeth, they are like
multi-coloured… I’m loads
bothered” (girl, aged 14)
appreciate the appearance of teeth which may be classified as having a TFI of 4 or

9, see Figs. 7.1 and 7.4, respectively. A sample of 478 young people, with a mean
age of 15.7 years, completed a modified version of OIDP. They were asked how
often they had experienced problems with their mouth or teeth in relation to seven
daily performances: eating, speaking and pronouncing clearly, cleaning teeth, sleep-
ing and relaxing, smiling without embarrassment, maintaining emotional state, and
enjoying contact with people. Significantly more females than males reported them-
selves to be affected on at least one daily performance. Overall, young people who
reported either oral impacts on their daily performance and/or discoloration of
upper anterior teeth were more likely to be dissatisfied with both their oral condition
and their dental appearance.
A similar study in Brazil also investigated the impact of fluorosis using a modi-
fied version of OIDP, this time with 513 schoolchildren aged 6–15 years [15]. No
differences in impact on daily activities (eating, speech, oral hygiene, sleep, smil-
ing, emotional stability, studying, and socializing) were found between those nor-
matively assessed as having fluorosis or not. Robinson and coworkers [30] issued
the CPQ11–14 to a sample of 174 12-year-old Ugandan children, 24 % of whom had
dental fluorosis. They reported that more participants with socially noticeable fluo-
rosis (TFI>2) had impacts on their OHRQoL than those with mild or no fluorosis,
although the difference was not significant.
Studies in developed countries, where any fluorosis is likely to be less severe,
have suggested that there is no impact on OHRQoL [1, 31]. Indeed, a study of 8- to
13-year-old Australian children found that those with a TFI of 2 had better OHRQoL
than their peers with normal enamel [1]. However, it was not clear whether this could
be attributed to the “whiteness” of affected teeth or reduced caries incidence.
Impacts Relating to Amelogenesis Imperfecta
Although there have been comparatively few studies on the psychosocial aspects
of AI [32], it is evident that this condition has far greater impact than dental
fluorosis. This is not surprising in view of the often severe functional problems,
relating to dental hypersensitivity and tooth tissue loss, which may accompany
compromised aesthetics. The first, and landmark, study of the psychosocial
impacts of AI was conducted with a mainly adult population, although a few ado-
lescent participants were included [19]. Interestingly, social avoidance and dis-
tress were found to be greatest among younger patients. More recently, a mixed
method study involving children from a UK dental hospital has made a significant
contribution to our understanding of how AI affects younger people [16]. In-depth
interviews were conducted with seven children, aged 13–16 years. A further 40 AI
patients, aged 10–16 years, completed the CPQ11–14 as well as some additional
questions generated from the previous interviews. Participants reported impacts
relating to aesthetics as well as function. Children did not like to show their teeth,
especially for photographs and in social settings.
I don’t like smiling with my teeth because I don’t like them (girl, aged 13)
When all my friends are talking I’d want to join in but don’t want to show my teeth
(girl, aged 16)
For some children, tooth sensitivity was actually more of an issue than aesthetics.
It is the sensitivity more than the colour, the colour doesn’t bother me, it’s more the sensitiv-
ity (girl, aged 15)
If there was no problem with sensitivity, I’d drink faster and bite down on ice lollies and not
cringe when I think of it (girl, aged 13)
Impacts Relating to DDE of Unknown Etiology
The only study to utilize in-depth interviews to explore the impact of DDE was
conducted in the UK with populations receiving either a non-fluoridated or fluori-
dated (1 ppm) water supply [23]. A theoretical framework, based on symbolic inter-
actionism was used to guide and interpret the qualitative data. Twenty-one 10- to
15-year-old young people were interviewed, with TFI scores ranging from 0 to 5.
The impact of DDE was frequently described in terms of how much dental appear-
ance “bothered” the individual. Photographs of the teeth of two participants have
been included to illustrate the clinical severity of the DDE.
I don’t like the colour, I’m conscious about it, when I am talking I don’t like showing
them…. I’m actually quite bothered (boy, aged 15)
I always wanted to change my teeth, they are like multi-coloured… I’m loads bothered
(girl, aged 14) (Fig. 7.1)
I’ve got some marks on the side of these two teeth, but they don’t bother me (girl, aged 13)
Interestingly, DDE impacted most on individuals whose sense of self was defined
by appearance and who depended on perceived approval from others about
Fig. 7.2 Photograph of teeth

of a participant with
developmental enamel
defects who said: “I’m happy
with the way I am, it doesn’t
really matter what you look
like, its personality” (girl,
aged 12)
appearance. No association was found between gender, age, severity of DDE, and
the reported impacts. However, this research was the first to identify that a sense of
self may explain variation in the impact of DDE on young people. The following
selected quotes illustrate how DDE were found to impact variably on the partici-
pants, in terms of how they felt about their own dental appearance.
I don’t want to look at myself in the mirror ‘cos I know I’ll look horrible…. (girl, aged 14)
I’m happy with the way I am, it doesn’t really matter what you look like, its personality.
(girl, aged 12) (Fig. 7.2)
Another important finding was the degree to which children were teased or ques-
tioned about the marks on their teeth, particularly when new people were encoun-
tered. Again, there was considerable variation in how teasing and name-calling
impacted on young people, which may have related to how much importance the
individual placed on their appearance as a whole.
I don’t’ like the thing on my tooth and I don’t like my big ears. Whenever I get into an argu-
ment with someone that’s the first thing they go on about (boy, aged 11)
When people are being nasty they always say things about my teeth, I don’t really care (girl,
aged 12)
Whenever I go on holiday or when I meet some new friends I don’t know they say “I don’t
mean to be bad, but I think you’ve got something on your teeth there”… They thought I
wasn’t brushing them and stuff… (boy, aged 11)
Teasing and Bullying
Teasing, name-calling, and bullying are a common occurrence in childhood and

adolescence. Lovegrove and Rumsey [26] found that over half of their sample of
654 British 11- to 14-year-olds had encountered appearance-related teasing or bul-
lying. In a study of children with AI, 50 % reported being teased about their teeth
[16]. This figure concurs with findings from an earlier study of children with a range
of DDE, where 56 % stated that they had been subject to unkind remarks about their
teeth [22]. Although Marshman and colleagues [23] found variation in how teasing
and name-calling impacted on young people, for some young people, being subject
to teasing may be the motivation for seeking cosmetic treatment, and the clinician
needs to be sensitive to such issues. However, young patients may be self-conscious
and not always forthcoming about this matter, especially when meeting a dentist
they do not know well. An empathetic approach is clearly needed, and the dentist
should be able to direct patients to available support services, such as online anti-
bullying resources (www.kidscape.org.uk).
The Impacts of Treatment for Enamel Defects
Dental Anxiety
The management of DDE encompasses a wide range of treatment regimens, which

broadly aim to preserve tooth structure, prevent dental caries, reduce symptoms
such as thermal hypersensitivity, and improve dental appearance. Some children
face a lifetime of dental interventions in order to maintain their compromised denti-
tion, and this may present considerable demands in terms of treatment compliance
and costs for affected individuals and their families. Jälevik and Klingberg [33]
highlighted the impacts of repeated treatment episodes for 9-year-old Swedish chil-
dren with molar incisor hypomineralization (MIH). They found that children with
MIH were more dentally anxious and were more likely to exhibit clinical behavior
management problems than children in a control group. Interestingly, their longitu-
dinal findings for the same group of children, 9 years later, revealed that although
patients with MIH had poorer oral health (a significantly higher DMFT), they were
no longer more dentally anxious then their non-MIH controls [34]. Clinical impres-
sions suggest that children with AI may also be more dentally anxious than their
peers [35], but this has yet to be evidenced by research findings. It is hypothesized
that because these children frequently experience and anticipate oral pain from nor-
mally innocuous thermal, mechanical, and osmochemical stimuli, they understand-
ably become more dentally anxious.
Psychosocial Outcomes
Patient-reported outcome measures are becoming more recognized within pediatric

healthcare [36] but have yet to be well developed within dentistry. A recent Cochrane
systematic review sought to compare clinical-reported and patient-reported out-
comes (satisfaction with esthetics and sensitivity) following restorative care of chil-
dren with AI [37]. Unfortunately, no studies met the inclusion criteria, but it was
encouraging to see that the authors had recognized the need to seek children’s views
on what treatment outcomes were important to them.
To date, only one study appears to have considered the impact of treatment on
young people with DDE [22]. This service evaluation sought the views of 67 young
people, aged 7–16 years, who had received microabrasion and/or composite restora-
tions on their upper incisors for a variety of visible enamel defects. Participants
completed a simple 10-item questionnaire which was developed with service users.
There was also a free text box for patients to write further comments. Prior to any
intervention, children reported high levels of worry and embarrassment. However,
following treatment, children said they felt happier and were more confident.
I am a lot happier now, people don’t pick on me (girl, aged 10)
I cannot fault my treatment which has made me gain some confidence, which has helped me
in this difficult year of exams (girl, aged 16)
Interestingly, the study also revealed unmet treatment expectations as some

young people reported disappointment that their teeth “weren’t perfect” after inter-
ventions. This finding clearly highlights the need for clinicians to communicate
effectively and manage patient expectations more realistically at the outset of treat-
ment. The media and celebrity culture may be influencing children to desire an
unnaturally white and uniform dentition, which presents clinicians with ethical,
financial, and clinical concerns.
I was looking forward for seeing my teeth completely white but they were not completely
white. It looked better than it was but they should have said that it wasn’t going to do all my
teeth white (boy, aged 14)
It is encouraging to see that a more recent study, conducted with children with
AI, did seek young patients’ expectations at the outset of treatment [16]. The authors
asked 40 children what was the single most important thing they wanted from their
course of treatment? The majority (63 %) stated that they hoped for an improvement
in the color of their teeth, and 18 % said they wanted a better smile. For 10 %, a
reduction in tooth sensitivity was the most important outcome.
Timing of Interventions
Another consideration is how the timing of any dental treatment, particularly for
largely esthetic interventions, impacts on the individual. Clinical anecdote suggests
that some children, who have been previously unconcerned about their dental
appearance, are prompted to request treatment because of a significant social event
(e.g., being a bridesmaid at a wedding) or change in their circumstances.
One study explored the experiences of 11- to 12-year-old children with a variety
of visible facial and dental differences, including DDE, during their transition to
secondary (high) school [17, 20, 22]. A 2-week diary was developed with children
and incorporated both open and closed questions with space to include drawings.
Fig. 7.3 Extract from the

diary of 11-year-old girl who
had undergone microabrasion
of her incisal opacities prior
to moving to her new school
Children also completed the CPQ11–14. Participants discussed a variety of aspects

about the transition to secondary school including concerns about their appearance
in their new social environment.
I had like brown marks on the front two teeth, I didn’t know what they were going to say
about them…. it was a worry before I went to big school. (girl, aged 11)
Some children discussed their oral conditions such as cleft lip and how they dealt
with questions from peers about it, while others reported having sought treatment to
improve the appearance of enamel defects prior to starting secondary school
(Fig. 7.3).
It should be noted, however, that heightened appearance-related concerns were
not limited to oral conditions as some children stated that they had tried to lose
weight, have their hair cut, or not to wear glasses prior to the transition. This enquiry
demonstrated how impacts from DDE may be more or less important to a young
person at different times during their life course, and dental care professionals
should be sensitive to these issues when planning courses of treatment.
Another important consideration, relating to the provision of dental treatment, is
how this may impact on a child’s school attendance and social activities. The need
for frequent dental visits, often at a specialist practice some distance from home, is
likely to have a social impact on the child and their family. However, our review of
the literature failed to reveal any studies in this area.
In general, the evidence base is lacking to support the psychosocial benefits of
DDE-related treatment for young people. This should be a priority for future
research as it becomes increasingly important that treatments are justified and eval-
uated in terms of patient benefit. Longitudinal studies are paramount to consider
both the short- and long-term psychosocial effects of different dental interventions
and thereby develop and safeguard services for young people with DDE.
Social Judgments in Relation to Enamel Defects
Appearance-Related Judgments
There is a wealth of literature to support the association between an individual’s

appearance, especially facial appearance, and how they are perceived by others
[38]. A fascinating study by Dion showed that children who were considered less
attractive than other children would be viewed as more likely by an adult to have
committed a misdemeanor and were viewed as less honest [39]. The seminal work
by Langlois and colleagues [40] also demonstrated that attractive children were
rated more positively for a number of personal attributes than those considered
unattractive. Regrettably, we live in a society where appearance does matter, and
those who look different may elicit negative judgments which have important social
consequences, including even future job prospects.
Children’s Views of Other Children with Enamel Defects
The first study to consider how a child’s dental appearance influenced how their
peers and adults viewed them was conducted by Shaw [41]. Children, depicted in
photographs, as having well-aligned teeth and normal facial appearance were
judged to be better looking, more desirable as friends, more intelligent, and less
likely to behave aggressively than children with a malocclusion or cleft lip.
More recently, a similar methodology was employed to determine whether, or
not, young people made value judgments, or ascribed certain social attributes, to
other young people with visible enamel defects [21]. Focus groups were first con-
ducted with children aged 11 to 16 years to identify what terminology they used,
or judgments they made, in relation to photographs of teeth with a range of
DDE. Two common themes emerged from these discussions with participants
perceiving that people with DDE were “lazy” or “did not care about their appear-
ance” (Fig. 7.4).
Fig. 7.4 Children’s

judgments relating to this
photograph of a child with
severe dental fluorosis
included: [this person] “has
no personal hygiene,” “has
eaten too much syrup,” and
“is lazy”
The investigators then recruited 547 school children, aged 11–12 and 14–15 years,
to rate full-face photographs of a boy and girl using a social attribute questionnaire
that had been previously developed with young people. The 11 social attributes
included: kind, rude, clever, honest, cares about appearance, careful, lazy, confident,
helpful, stupid, and naughty. Half the participants were shown photographs of the
boy and girl with normal teeth, and half were shown digitally modified photographs
of the same children with a visible enamel defect affecting one upper incisor. The
key finding was that young people did make negative social judgments on the basis
of DDE. Age and socioeconomic status did not have an effect on raters’ scores, but
girls were more positive in their assessment than boys. Affected individuals may be
unfairly judged by others which may, in turn, impact on their self-esteem, social
interactions, and life prospects.
Summary and Clinical Implications
This brief review of the literature, albeit an emerging literature, suggests that hav-
ing a DDE can impact on children and young people in a variety of ways. Generic
oral health-related quality of life questionnaires have provided conflicting findings,
but qualitative enquires have given a richer and more meaningful insight into the
range and severity of psychosocial impacts. Appearance-related impacts are fore-
most with some children reporting embarrassment, upset, and reluctance to smile
or show their teeth in normal social interactions. In addition, some children may
experience dental hypersensitivity as well as compromised esthetics, which are
likely to have negative impacts on daily activities. For young patients requiring
extensive dental treatment, there is the potential to develop dental anxiety. Studies
have also shown that some children with DDE are subject to dental appearance-
related teasing and may incur negative social judgments from their peers. Most of
the research to date has been conducted on the impact of DDE in the permanent
dentition with little knowledge about the nature or severity of the impact of DDE
on younger children.
Some individuals with a visible difference cope better than others but the reasons
for their resilience have not been fully elucidated. This observation is supported by
the finding that there is no simple correlation between the severity of the enamel
defect and the resultant impact. Further research, in collaboration with social sci-
ence experts, is indicated to explore these complex and dynamic relationships,
throughout childhood and adolescence.
The “take-home” message for clinicians is that children and young people with
DDE require an empathetic and insightful approach. Every effort should be made to
provide timely and aesthetic care, which addresses the young patient’s individual
concerns and circumstances. However, unrealistic treatment expectations may be
encountered, and these need to be met with good communication and appropriate
support. It is important that robust pediatric patient-reported outcome measures are
developed for future use, so that we can be sure that our treatment is actually help-
ing to reduce the psychosocial impacts of having an enamel defect.
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Examination and Treatment
Planning for Hypomineralized 8
and/or Hypoplastic Teeth
Bernadette K. Drummond and Winifred Harding
Abstract
When children present with teeth with developmental defects of enamel (DDE),
achieving long-term successful outcomes for the teeth is dependent on establish-
ing a diagnosis of the problems and on immediate, short- and longer-term treat-
ment planning. Good records (medical and dental history as well as clinical
radiographic, photographic, and histologic examination) that are available for
successive clinicians who treat the child are also important. It is also important
to consider referral for medical evaluation if it is thought the defects are related
to a general systemic or genetic condition that has not been investigated. This
chapter provides guidance on the process of examination required to establish a
diagnosis and possible treatment options including the impact on the developing
occlusion when those options may involve extractions.
Introduction
It can be difficult to diagnose if enamel is hypomineralized or hypoplastic and to

establish how the appearance, color, and position of defects may affect the quality of
the enamel. Currently there is no recommended clinical charting for developmental
defects of enamel (DDE) that reflects the diagnosis and indicates how the teeth should
be managed. Establishing a diagnosis can identify potential long-term issues includ-
ing the impact of the type of defect on enamel bonding. There is also not a good evi-
dence base for restorative management or bonding protocols for DDE-affected teeth.
B.K. Drummond, BDS, MS, PhD (*)

Department of Oral Sciences, Faculty of Dentistry, University of Otago,
310 Great King Street, PO Box 647, Dunedin 9054, New Zealand
W. Harding, BDS, MDS
Department of Oral Sciences, Discipline of Orthodontics, Faculty of Dentistry,
University of Otago, 310 Great King Street, PO Box 647, Dunedin, New Zealand

100 B.K. Drummond and W. Harding
Despite many papers describing the structure and composition of defective enamel
(see Chaps. 5 and 6), there is still limited understanding of how enamel with decreased
mineral and/or with increased protein content can be successfully managed with cur-
rently available restorative procedures. Understanding the diagnosis will allow the
immediate needs to be considered including management of sensitivity, poor esthet-
ics, and posteruptive breakdown (PEB). Because the defects are usually diagnosed in
young children, once the immediate problems have been managed, an intermediate
management plan should be developed to preserve the teeth until permanent restora-
tions can be placed, often over a decade later. Early management may include using
preventive materials to decrease caries risk and sensitivity, masking defects to improve
appearance, and temporarily and/or permanently restoring hypoplastic defects. It can
seem tempting to extract teeth when only one or a few teeth are affected, but full
assessment of occlusal development is important to consider orthodontic treatment
needs. Young patients have a wide range of coping skills, and sedation or general
anesthesia may be required to optimize outcomes. There are also financial implica-
tions. While funding may be available to support dental treatment during childhood, it
may not be as accessible in early adulthood when definitive restorations are planned.
Long-term planning should therefore also take in to consideration the ability of the
child/family to afford anticipated treatment. Families require a significant amount of
knowledge of the problems associated with DDE to understand that the affected teeth
will require a lifetime of dental care even when they remain caries and erosion free.
This chapter considers what should be included in the examination, diagnosis, and
treatment planning when children present with teeth with DDE.
Description of Enamel Defects
The appearances of DDE have been described in previous chapters (Chaps. 1, 2, 3,

and 5) but are summarized again in Table 8.1. While the descriptors have been
mainly developed for epidemiological studies, they are useful clinically to help
diagnose the type of defect.
Table 8.1 Descriptions of enamel defects that have been used in epidemiological studies
Demarcated
Type of defect Extent of defects Diffuse opacities opacities
Normal Less than one third Diffuse lines White cream
Diffuse opacity Between one and two Diffuse patchy Yellow brown
thirds
Demarcated opacity At least two thirds Diffuse confluent
Hypoplasia Staining
Hypoplasia pits Pits
Hypoplasia grooves Loss of enamel
Hypoplasia, missing enamel,
discoloration
Any other
8 Examination and Treatment Planning 101
Clinical History
As many opacities and hypoplastic defects appear to have no obvious cause, a care-
ful and accurate history can pinpoint the timing in relation to possible associated
medical events when the defects may have occurred. There will often be a history of
repeated attempts to restore teeth with DDE or of a child who is often described as
uncooperative. This suggests that because of the sensitivity of affected teeth, chil-
dren have been more anxious, and local anesthesia has not been successful [1]. In
older children, first molars in molar incisor hypomineralization (MIH) may have
already been extracted. Table 8.2 summarizes the information that is useful in the
clinical history.
The problems, signs, and symptoms given by the child should be recorded. It can
sometimes be difficult to elicit concerns or a pain history from younger children but
suitable questions often help identify the issues, as suggested in Table 8.3 and
described in Chap. 7.
Table 8.2 Information from the clinical history

Information Relevance
Family history May suggest a genetic cause (Chap. 5)
Birth history Neonatal events (Chaps. 1, 2, and 4)
Pregnancy history Pregnancy history and mother’s health
Childhood systemic Timing of childhood illnesses (Chap. 4)
illnesses
Drug and medication Evidence of drugs, medication, and supplements affecting enamel
history development (Chaps. 2 and 3)
Allergies Enamel defects in with conditions such as celiac disease (Chap. 4)
Hypocalcemia Associated with prematurity, Vitamin D deficiency, and maternal
diabetes (Chaps. 1 and 2)
Nutritional problems Exclusive breast feeding beyond 6 months, Vitamin D deficiency
(Chaps. 1 and 2)
Caries history From the primary dentition. If only second primary molars
restored – suggestive these teeth may have had DDE
Table 8.3 Children’s history indicating teeth problems

Question/comment Explanation
It hurts to brush my teeth Teeth are too sensitive
My teacher says I don’t clean my teeth Many people think opacities and other DDE are due
properly to a lack of brushing
Mother describes child never smiling Suggests that children do not like their appearance
My friends make fun of me Demonstrates a social problem for the child
My teeth have sharp edges An issue for children with hypoplastic or fractured
enamel
Can’t eat ice cream Indicates a significant sensitivity problem
Parents say child eats slowly or refuses Suggests sensitive teeth and food trapping
some foods
Clinical Examination
The clinical examination should note the sites, size, and appearance of DDE on
individual primary and/or permanent teeth. This can help to differentiate between
isolated insults during development or a genetic- or systemic-related problem that
has affected all the teeth. DDE in selected primary teeth can indicate a potential
problem in permanent teeth. Developmental defects of the primary second molar
alone are suggestive of hypomineralized second primary molars (HSPM) which are
predictive of MIH as discussed in Chap. 3. Developmental defects that affect all the
primary teeth may indicate a more generalized impact in the permanent dentition
(Chaps. 4 and 5). The texture and color of the enamel indicate the presence of hypo-
plasia and/or hypomineralization. The darker the color, particularly in MIH, the
higher the enamel protein content, indicating increased risk of cohesive failure of
bonded restorations [2]. Texture can be determined by gently running a probe across
the surface. Enamel that is opaque may have a relatively smooth texture reflecting
the fact that the surface enamel has mineralized further after eruption. However it is
important to remember that from the bonding perspective, the subsurface is still
hypomineralized. Color and texture will partly determine the restorative approaches.
In hypomineralized enamel without hypoplasia or breakdown, attempts can be
made to improve the appearance using microabrasion with and without bleaching or
possibly resin infiltration. This is discussed further in Chap. 11. Areas of posterup-
tive breakdown or hypoplasia should be noted as well as the position of normal
enamel that can be utilized to optimize bonding and achieve a sound marginal seal
for restorations. In most MIH-affected first permanent molars, there is a band of
relatively normal enamel at or below the gingival margin as shown in Fig. 8.1. This
allows for good permanent crown margins in late adolescence once pulps have
matured and teeth have erupted to provide an acceptable crown height. The chal-
lenge in a young child is how to achieve protection of the crowns and pulps of
affected teeth until late adolescence (Chaps. 9 and 11 discuss management options).
Care should be taken when diagnosing caries. What appears to be caries visually
may be found to be sound dentine with posteruptive enamel breakdown after the
surface has been cleaned and dried. This is important as non-carious dentine should
Fig. 8.1 View of extracted

lower first molar crown
showing “normal” enamel at
or below the gingival margin
(Courtesy of Dr. Rami Farah)
be preserved when restoring hypomineralized teeth and so consideration needs to be

given to dentine, as well as enamel bonding in the restorative technique. This is
discussed further in Chap. 11.
Radiographic Examination
Panoramic radiography is essential to establish the presence or absence of all

permanent teeth and to assess the stage of development of the dentition. This is
very important if extractions are being considered as part of the management
plan. Calcification of the second premolar crowns will be evident in the early
mixed dentition. However, calcification of the third molar crowns does not begin
until 7–10 years of age, and this should be taken into account when taking radio-
graphs and planning treatment (Fig. 8.2). The developmental stages of each
tooth and anomalies in shape and size as well as in eruption paths should be
recorded to consider the possibility of other associated conditions. Bitewing
radiographs can help determine if caries is occurring alongside hypomineraliza-
tion when the shapes of radiolucent lesions are compared and the dentine is
examined (Fig. 8.3).
Fig. 8.2 Panoramic

radiograph of a 9-year-old
boy with severe hypomineral-
ization of the upper first
molars. Third molars are not
evident
Fig. 8.3 Right posterior

bitewing radiograph of an
11-year-old girl with gold
overlays on the upper and
lower right first molars. Note
the hypomineralized enamel
on the mesial and distal
surfaces and suspected
enamel caries on the mesial
of the lower first molar
Histological Examination
When a systemic or genetic cause for the DDE is suspected, it is recommended that
any available teeth be examined histologically. The histological appearance will
help to determine a more accurate diagnosis and provide the clinician with a better
understanding of the condition and likely behavior of the tissues when planning
restorative care. Histology can be carried out on exfoliated primary teeth or ideally
on permanent teeth if they become available.
Medical Examination
Teeth with DDE may be associated with a systemic condition or a syndrome.

Occasionally a problem has not been diagnosed, and where this is suspected, chil-
dren should be referred to a pediatrician with the relevant orofacial history and
concerns. It is useful to include copies of radiographs or histology reports which can
be added to the general medical record. Where a genetic cause is determined, advice
may be sought from a geneticist to determine the genes involved or to give the child
and parents more information about the inheritance pattern.
Assessment of Growth and Development
Early assessment of growth and development is essential in children who present

with DDE. Where possible, an orthodontic opinion should be included in the
assessment, particularly if there is an associated malocclusion and/or consider-
ation is being given to extracting first permanent molars because of their poor
prognosis. The implications of long-term restorative needs have to be weighed up
against possible outcomes in the developing dentition if teeth are removed, par-
ticularly if there is a malocclusion that will worsen with early loss of teeth. It is
important that the clinician informs the orthodontist of the long-term prognosis of
the teeth including the likelihood of complex restorative care throughout adult-
hood. In cases of defects with severe posteruptive breakdown (PEB) or hypoplasia
with associated malocclusion, positioning of teeth is important for future prosth-
odontic management. The primary care dentist or pediatric dentist can play an
important role in coordinating prosthodontic and orthodontic evaluations to deter-
mine the best long-term plan. Extraction of teeth may at first seem a useful solu-
tion, but careful planning is needed to limit later occlusion problems. It is
important to consider caries risk, as extracting teeth in children who have a history
of caries and are likely to remain at risk may not be a sensible solution for the
whole dentition in the long term. This is particularly important if subsequent fixed
appliance orthodontic treatment is going to be needed to close extraction spaces,
upright second molars, or correct an existing malocclusion. Space analysis can
predict relationships of the teeth to the arches and space available.
Table 8.4 Information from growth and development assessment

Extraorally Skeletal pattern
Face height
TMJ
Symmetry
Lip competency
Intraorally Permanent and primary molar relationships
Canine relationships (primary or permanent depending on age)
Position and inclination of canines
Crossbite with/without displacement
Position of midlines
Inclination of upper and lower incisors
Overjet and overbite
Crowding or spacing of the teeth
Curve of Spee
Teeth Teeth – present and unerupted (radiographs)
Caries – clinical and radiographic
Teeth defects clinical and radiographic
Other anomalies – missing, supernumerary, malformed teeth
Space analysis Amount or lack of space should be estimated
Photographs Important record for longer-term recording of the changes
Study models Important record of the developing occlusion
Information to Be Recorded
Because children with DDE will face ongoing treatment needs, it is important to
produce good records that can be used throughout childhood and adolescence.
Table 8.4 suggests the clinical and orofacial developmental features that should be
recorded.
Treatment Planning
Treatment planning for children with DDE will determine the stages of treat-
ment to optimize long-term survival of the teeth [3]. Many children with DDE
do not cope well with dental treatment. This will play a significant role in the
decision-making process as many options require the child/adolescent to cope
with complex long-term restorative and/or orthodontic care. Planning should
optimize the timing of treatment and minimize the need for repeated procedures
when sedation or general anesthesia is needed. Financial considerations will
also impact on treatment choices and need to be acknowledged both for short-
and longer-term treatment plans. Table 8.5 summarizes possible management
options in the immediate, short-term and long-term management of teeth with
enamel defects.
Table 8.5 Short-, medium-, and long-term management options

Immediate Explanation
Controlling sensitivity Allows good oral hygiene and child can manage treatment
(Chap. 9)
Preventing dental caries Teeth with DDE are more susceptible to faster caries
progression in hypomineralized or hypoplastic teeth (Chap. 9)
Temporary restorations Useful in the short term but important to avoid repeated efforts
to restore or seal teeth to avoid child developing dental anxiety
Improving enamel Long-term protection, improved bonding, decrease risk of
fracture
Improving aesthetics Very important in the anterior region to improve child
self-esteem
Medium term (3–10 years) Explanation
Controlling sensitivity Needed until permanent restorations are provided in molar
teeth unless temporary coverage has been possible
Preventing dental caries Home prevention, frequent recalls, professional fluoride
treatments, and sealing where appropriate (Chap. 9)
Restoring defects Temporary restorations need regular monitoring and resealing
(Chap. 11)
Managing pulp health Dentine and enamel should be sealed to protect pulp and allow
maturation. Pulpal exposure or infection can be managed with
a range of procedures that can maintain the teeth until
long-term solutions are decided [4]
Acceptable aesthetics Important in childhood and adolescence for confidence
(Chap. 7)
Temporary crowns Stainless steel crowns are an excellent solution for primary and
permanent molars. Polymethyl methacrylate (resin) crowns
provide acceptable outcomes in dentitions with AI [5]. Both
support the occlusion until early adulthood (Chaps. 10 and 11)
Extraction of teeth Extraction of teeth is an option in some dentitions. Important
Orthodontic care to consider timing and possible need for associated orthodontic
care [7].
Long term Explanation
Cast metal overlays Cast metal overlays can be successful in molars with moderate
hypomineralized defects and PEB or wear (Chap. 11)
Ceramic onlays Ceramic onlays may be considered for molar teeth.
Unacceptable wear of opposing teeth with immature enamel
may occur [5]
Veneers Porcelain veneers provide excellent aesthetics anteriorly. Not
recommended until complete eruption has occurred in late
adolescence or early adulthood (Chap. 11)
Crowns Several options available when enough tooth tissue to support a
crown. Success is dependent on temporary care that is provided
through childhood and adolescence (Chap. 11)
Practical Management When Extractions Are Being Considered
When planning the longer-term management of hypomineralized or hypoplastic

teeth, an orthodontic consultation is important to inform the child and parents of
possible outcomes for the occlusion and what can be done if teeth are extracted.
It is important that the orthodontist is aware of the prognosis of the teeth so that
they can include this in their assessment of the risks and benefits of possible orth-
odontic options. As it is not always possible to involve an orthodontist, the follow-
ing is a guide when planning extraction of first permanent molars. It allows
appropriate information to be given to the child and parents. It is recommended
that details be carefully recorded and given to the family in written form. This
includes clinical and radiographic details and photographs. It can help answer
questions about the treatment that may come many years later. Details that should
be recorded include:
1. Are teeth restorable with good long-term prognosis and without repeated
restorations?
2. Are the third molars developing? Are there other missing teeth?
3. Are the second molars developing normally with acceptable eruption paths to
erupt into functional occlusion? What are their stages of development?
4. Are all the premolars developing normally with normal eruption paths?
5. Are other teeth hypomineralized? Is this a generalized problem?
6. If there is crowding, what impact will the extractions have?
7. What is the anterior occlusion including overbite and overjet? Will the overbite
be acceptable if molars are extracted or will it increase? Is there a lip trap?
8. What is the facial growth pattern?
These questions and the following information provide guidance on planning

whether to extract or keep first permanent molars with defects. There are generally
four possible options:
1. Extract immediately if age and stage of development are appropriate or the tooth
is not restorable, even temporarily
2. Delay extraction to optimize the eruption of surrounding teeth
3. Delay extraction until done as part of orthodontic treatment
4. Keep and plan the path to permanent restoration of the tooth/teeth
Outcomes of Extraction of First Molars
Where conditions are favorable, satisfactory space closure can be achieved when
first molar extractions are done in children and young adults [8–10]. Williams and
Hosila [11] noted that extraction of first permanent molars was associated with less
effect on the profile and significantly more likelihood of third molars erupting than
with premolar extractions. First molar extraction will not always relieve crowding
posteriorly, but improvements in third molar eruption have been reported [6, 12,
13]. In the majority of children with early loss of permanent first molars before
12 years of age, third molar development appears to be accelerated on the side of the
extraction [14]. Figure 8.4 a–c shows the outcome of extracting a single lower molar
at a time to optimize eruption of the second permanent molar.
Fig. 8.4 Panoramic a

radiographs showing (a) a
broken down lower left first
molar, (b) 2 years following
extraction, (c) 9 years
following extraction showing
good position of early
erupting lower left third
molar
The following can be considered:
1. In dentitions with excess space in the arches, extractions may leave permanent
spaces or orthodontic treatment may be needed to close unacceptable spacing.
2. When molars are extracted in one quadrant only, overeruption of the opposing
molar or occlusal interferences may occur. Compensating extractions (i.e.,
removal of the opposing tooth) are not always advised. Balancing extractions
(i.e., removal of the contralateral tooth) can be considered after the available
space and anterior occlusion are taken into account. In some instances a balanc-
ing extraction may be a premolar on the opposite side especially where the oppo-
site molar is not compromised. There can be a risk of midline shift when only
one molar is extracted [15].
3. When a lower first molar is extracted, occlusal forces can influence mesial and
lingual tilting of the second molar because of the thinner lingual plate. Lingual
positioning may result in a scissor bite or nonworking side interferences that can
Fig. 8.5 Panoramic

radiograph of an adolescent
who had both upper first
molars extracted 2 years
previously
Fig. 8.6 (a) Panoramic of

a
9-year-old female with an
orthodontic plan to have all
first molars extracted (severe
hypomineralization). Note
positions of lower second
premolars. (b) Panoramic
3 years after the extractions.
Note eruption paths of lower
second premolars
cause unwanted tooth wear. Poor interproximal contacts can lead to food impac-
tion and difficulty in cleaning. This is less likely to occur with an upper first
molar extraction, as the upper second molar will usually erupt into a good posi-
tion as long as the second molar is unerupted at the time of the extraction as
illustrated in Fig. 8.5.
4. Early extraction of first permanent molars before 8 years-of-age may result in
distal drifting, tilting, and rotation of unerupted second premolars even in well-
aligned arches. In severe ectopic eruption, the second premolar may impact
against the second molar as it erupts. Where a distal eruption path of the second
premolar is detected, the second primary molar could be extracted at the same
time as the first molar extraction to encourage a vertical eruption path for the
premolar (Fig. 8.6a, b).
Fig. 8.7 Patient in mixed

dentition illustrating deep
bite which would probably
worsen if the first molars
were extracted
5. An increase in overbite can occur following the early extraction of first molars.
Retroclination of the lower incisors worsens in children with previously pro-
clined upper incisors and increased overjet [16]. In children with decreased
facial height, crowded lower anteriors, or a deep overbite, early extraction of the
first molars is contraindicated without management to prevent further problems
in the anterior occlusion (Fig. 8.6).
6. Where there is a skeletal or dental malocclusion, extractions may be timed to
utilize space to correct the malocclusion:
(a) In a class II occlusion with maxillary protrusion, upper first molar spaces
may be required for anterior teeth retraction.
(b) With a lower lip trap and increased overjet, extraction of lower first molars
can result in lower incisor retroclination which may increase overjet and
complicate treatment (Fig. 8.7).
(c) In bimaxillary protrusion, first molar extraction spaces may be required for
anterior retraction.
(d) In severe crowding, first molar extraction spaces may be required to alleviate
the crowding.
(e) Distal drift of the lower premolars may occur after lower first molar extrac-
tions to allow improvement in alignment of the anterior teeth where the over-
jet and overbite are acceptable, but this rarely occurs in the upper arch.
(f) In class III malocclusions, lower first molar extraction spaces may be needed
for lower anterior teeth retraction.
(g) With maxillary constriction, the first molars may be needed for expansion
devices.
(h) With a skeletal anterior open bite, early extraction of first molars may be
advantageous as part of orthodontic management.
7. To optimize the eruption of second molars into first molar positions, the timing
of extractions, particularly the lower, is important. Ideal timing is usually around
9–10 years of age, when the bifurcation dentine of the second molar is mineral-
izing with the beginning of root formation [17, 18] (Fig. 8.2). Temporary mea-
sures may be necessary to retain the teeth in an infection- and pain-free state
until the ideal time for the extractions. This timing will encourage the eruption
of the second molar (often early) into contact with the second premolar in an
uncrowded dentition.
Conclusion
This chapter has covered aspects of clinical and radiographic examination and
treatment planning for children with DDE. It has provided some guidance when
considering options to extract teeth that have DDE. Careful planning that includes
the management of sensitivity and esthetics will help the child to care for their
teeth and develop skills to cope with dental treatment. An important aspect is the
need to keep good records of both the original diagnoses and initial treatments as
teeth with defects will require long-term treatment and records can be given to
successive clinicians to aid in planning further care. Although young children
may be difficult to manage, they deserve even more attention when they have
DDE because the care given in the early permanent dentition can have a pro-
found impact on the outcomes for the life of the teeth and on the child’s ability
to continue seeking dental care.
References
1. Jälevik B, Klingberg G. Dental treatment, dental fear and behavior management problems in
children with severe enamel hypomineralization of their permanent molars. Int J Paediatr
Dent. 2002;12(1):24–32.
2. William V, Burrow M, Palamara J, Messer L. Microshear bond strength of resin composite to
teeth affected by molar incisor hypomineralization using 2 adhesive systems. Pediatr Dent.
2006;28(3):233–41.
3. Lygidakis N. Treatment modalities in children with teeth affected by molar-incisor enamel
hypomineralisation (MIH): a systematic review. Eur Arch Paediatr Dent. 2010;11(2):65–74.
4. American Academy of Pediatric Dentistry. Guideline on pulp therapy for primary and imma-
ture permanent teeth. Pediatr Dent. 2010;35(6):235–42.
5. Zagdwon A, Fayle S, Pollard M. A prospective clinical trial comparing preformed metal
crowns and cast restorations for defective first permanent molars. Eur J Paediatr Dent.
2003;4(3):138–42.
6. Sandler P, Atkinson R, Murray A. For four sixes. Am J Orthod Dentofacial Orthop.
2000;117(4):418–34.
7. Koch M, Garcia-Godoy F. The clinical performance of laboratory-fabricated crowns placed on
first permanent molars with developmental defects. J Am Dent Assoc. 2000;131(9):1285–90.
8. Jälevik B, Moller M. Evaluation of spontaneous space closure and development of permanent
dentition after extraction of hypomineralized permanent first molars. Int J Paediatr Dent.
2007;17(5):328–35.
9. Mejare I, Bergman E, Grindefjord M. Hypomineralized molars and incisors of unknown ori-
gin: treatment outcome at age 18 years. Int J Paediatr Dent. 2005;15(1):20–8.
10. Teo T, Ashley P, Parekh S. The evaluation of spontaneous space closure after the extraction of
first permanent molars. Eur Arch Paediatr Dent. 2013;14(4):207–12.
11. Williams R, Hosila L. The effects of different extraction sites upon incisor retraction. Am J
Orthod. 1976;69(4):388–410.
12. Gill D, Lee R, Tredwin C. Treatment planning for the loss of first permanent molars. Dent
Updat. 2001;28:304–8.
13. Ong D-V, Bleakley J. Compromised first permanent molars: an orthodontic perspective. Aust
Dent J. 2010;55(1):2–14.
14. Yavuz I, Baydas B, Ikbal A, Dağsuyu M, Ceylan I. Effects of early loss of permanent first
molars on the development of third molars. Am J Orthod Dentofacial Orthop.
2006;130(5):634–8.
15. Çağlaroğlu M, Kilic N, Erdem A. Effects of early unilateral first molar extraction on skeletal
asymmetry. Am J Orthod Dentofacial Orthop. 2008;134(2):270–5.
16. Richardson A. Spontaneous changes in the incisor relationship following extraction of lower
first permanent molars. Br J Orthod. 1979;6(2):85–90.
17. Cobourne M, Williams A, McMullen R. A guideline for the extraction of first permanent
molars in children. London: Royal College of Surgeons of England; 2009.
18. Thunold K. Early loss of the first molars 25 years later. Rep Congr Eur Orthod Soc.
1970:349–65.
Managing the Prevention of Dental
Caries and Sensitivity in Teeth 9
with Enamel Defects
Felicity Crombie and David J. Manton
Abstract
Developmental defects of enamel (DDE) may affect either or both the quality
and the quantity of enamel and as such potentially have implications for caries
risk and hypersensitivity. The management of these teeth in terms of caries pre-
vention/tooth structure preservation and sensitivity often overlaps and so is pre-
sented together. This chapter proposes strategies to address the fundamental
deficiencies of the enamel and to optimize clinical and patient outcomes. Earliest
possible intervention is advocated and includes oral hygiene, diet and salivary
advice, mineralization therapy, and surface sealants. These are all broadly famil-
iar to the clinician from the caries context, but some modifications are recom-
mended when applied to developmental defects. Less familiar techniques, such
as the potential applications for recently developed infiltrant resin materials, as
well as full coverage “sealants” for severely affected teeth, are also presented.
Introduction
When considering dental caries and sensitivity, the clinician should understand that
enamel defects, either developmental or acquired, fall within one or both of two
categories: defects of enamel quantity and/or defects of enamel quality. The relative
caries or posteruptive breakdown (PEB) risk, mechanism of hypersensitivity, and
therefore appropriate management are to a large extent determined by the type of
defect. Hypersensitivity tends to be associated more with hypomineralized enamel
F. Crombie, BDSc (Hons), PhD

Growth and Development Unit, Melbourne Dental School, University of Melbourne,
Melbourne, VIC 3010, Australia
D.J. Manton, BDSc, MDSc, PhD (*)
Growth and Development Unit, Melbourne Dental School, University of Melbourne,
720 Swanston St, Carlton, VIC 3053, Australia

114 F. Crombie and D.J. Manton
than with hypoplastic enamel; however, each individual should be managed in a

manner appropriate to their particular presenting problems.
The enamel should be the hardest tissue in the human body and, if healthy, allows
the teeth to withstand normal functional loading. The enamel protects the underly-
ing dentine and therefore limits the relatively more rapid progression of caries and
wear in dentine compared to enamel – this protection or lack of it can also moderate
dentinal sensitivity. In order to fulfill these demands, enamel is a highly specialized
and organized tissue and aberrations often result in catastrophic reductions in
performance, as discussed in Chap. 6. The underlying mechanisms leading to hyper-
sensitivity are probably linked to reduced enamel thickness in the case of hypopla-
sia and increased porosity in severely hypomineralized enamel. Generally (but not
always) the hypersensitivity, particularly in hypomineralized enamel, occurs
following PEB and in some cases is exacerbated by an underlying pulpitis [1]. Many
of the properties and processes contributing to hypersensitivity are also implicated
in caries risk, and so management strategies often overlap. Management can be
complicated by the age and compliance of the patient [2, 3].
Dental Caries and Erosion Risk
Research has established that enamel surface integrity and bacterial adhesion are
important in caries initiation. While it has been well documented in the primary
dentition that the relatively reduced thickness and poorer structure of enamel can be
linked to an increased rate of caries progression [4, 5], the evidence in the perma-
nent dentition is equivocal. Enamel defects are often vulnerable from both perspec-
tives with hypoplasia or PEB not only reducing the thickness of the protective
enamel layer but potentially creating non-cleansable contours. Furthermore in
hypomineralized defects apparently intact surfaces frequently display surface irreg-
ularities and porosities on a microscopic scale (Fig. 9.1 – SEM image of pitted
enamel surface). The susceptibility of these qualitative defects to dental caries can
be compounded by increased porosity and in some cases, such as in molar incisor
hypomineralization (MIH) and hypocalcification/hypomaturation types of amelo-
genesis imperfecta (AI), decreased mineral and increased protein content, and
decreased hardness and increased solubility of enamel [6–8]. The management of
Fig. 9.1 Surface of a

clinically intact MIH lesion
viewed under a scanning
electron microscope showing
characteristic surface
irregularities (×1000 mag)
9 Managing the Prevention of Dental Caries and Sensitivity 115
Fig. 9.2 MIH-affected tooth

with severe loss of structure
and caries before complete
eruption
hypoplastic, quantitative defects usually focuses on establishing a cleansable sur-

face, with the use of materials such as flowable resin composite to replace deficient
enamel and create a smooth and cleansable surface. However, more extensive
restorative care such as full coverage restorations may be required if the hypoplastic
defects are severe [2]. It should be noted that in the case of enamel defects, estab-
lishing cleansable surfaces is not purely related to contour and may also require
control of sensitivity to allow adequate oral hygiene to be performed [2, 3].
For qualitative defects, improving physical and chemical properties to optimize
preservation and improvement of hypomineralized enamel tissue is the primary goal.
Most strategies utilized clinically for hypomineralized enamel defects are based on
the standard caries disease model, such as minimization of caries risk. However,
some of these cannot always be applied directly to developmentally defective tissues
because of the defective structure [2, 9]. Most particularly, in severe hypomineraliza-
tion cases, intervention must be instituted as early as possible since significant dam-
age can occur even before the crown is fully erupted (see Fig. 9.2). Anterior teeth are
less affected by PEB and are less likely to become carious after enamel loss. However,
molar teeth with PEB are at risk and should be closely monitored [10].
Prevention of Dental Caries and Erosion
To achieve success with any preventive strategy, early and accurate diagnosis is
critical (see Chaps. 1, 2, 3, and 5). Once a diagnosis has been made, it is essential to
emphasize the importance of general preventive principles for these teeth and to
recognize that otherwise acceptable levels of care and compliance may be insuffi-
cient for caries prevention in these more vulnerable teeth. Where clinicians note that
primary second molars or permanent incisors have DDE, this indicates the first
permanent molars may also be affected and consideration should be given to alter-
ing recall timing and/or frequency to facilitate earliest possible intervention [11,
12]. If the case appears to be severe or complex, especially for genetic conditions
such as AI or where sedation or general anesthesia may be required, early specialist
referral to plan longer-term interventions may be the most appropriate management
a general practitioner can provide (Chaps. 10 and 11).
Oral hygiene instruction should be undertaken including advice to ensure par-
tially erupted teeth are cleaned appropriately – often using a buccolingual stroke
with a soft brush for partially erupted molars to improve efficacy of plaque removal
during the long eruption phase [13]. Given defects often manifest at an early age,
before independent oral hygiene is recommended, the use of disclosing agents can
assist both children and parents to better visualize deposits on the teeth. For sensi-
tive teeth the simple suggestion to use warm water with the toothpaste when brush-
ing may be helpful. Defects affecting the primary dentition may encourage increased
cariogenic bacteria colonization with consequent higher caries risk. Although this
has not been a consistent finding, it may still be prudent to include advice to reduce
caries risk even when there has been little past evidence of caries [14, 15].
Dietary counseling, ideally in the form of a motivational interview where by
providing information in a collaborative manner, encouraging willingness, ability,
and readiness the clinician facilitates rather than directs change [16], is recom-
mended [17]. This may include advice on caries prevention as well as on managing
hypersensitivity, which is often as simple as avoiding or decreasing causative fac-
tors – i.e., cold drinks or food. As with standard dietary counseling, the role of fer-
mentable carbohydrates (especially sucrose), particularly in terms of frequency and
duration, should be discussed along with strategies to minimize exposures and ideas
for healthier alternatives [18]. Intrinsic and/or extrinsic acids may also warrant
some discussion not only in terms of exacerbating sensitivity but also, particularly
in generalized conditions such as AI, because they may accelerate enamel loss in the
form of erosive tooth wear. The influence of salivary characteristics should also be
considered and potentially integrated into dietary counseling. As there is some evi-
dence to suggest that salivary protection is less favorable in children affected by
MIH, testing of salivary characteristics such as flow and consistency may be of
benefit [14].
Preventive Agents
Another core component of caries prevention and desensitization is the use of fluo-
ridated agents and calcium-based remineralizing agents. Ideally, for qualitative
defects, the aim is not merely to remineralize any posteruptive demineralization but
to address the primary mineral deficiency [19]. Studies of MIH, both in vivo and
in vitro, suggest that casein phosphopeptide-amorphous calcium phosphate with
Fig. 9.3 Polarized light images of surface layer observed on both intact and PEB surfaces of MIH-
affected teeth (in water, ×5 mag.). White/gray indicates reduced porosity (≤5 %), brown/orange
indicates increased porosity (>5 %)
and without fluoride (CPP-ACFP/ACP) application can improve enamel mineral

content and reduce porosity both on exposed surfaces and deeper within the enamel
tissue (see Fig. 9.3) [19, 20]. It is believed that a smoother surface, denser structure,
and additional mineral content, especially if it is in the more chemically favorable
forms of fluorapatite or fluoridated hydroxyapatite, should putatively reduce caries
and breakdown risk [19].
The action of CPP-based products relates to the ability of this milk-based protein
to stabilize calcium and phosphate in high concentration and provide supersaturated
ionic calcium and phosphate at and below the tooth surface. This then allows the
diffusion of calcium and phosphate ions down a concentration gradient into the
lesion at much higher concentrations than otherwise would be possible driving rem-
ineralization [21]. Reducing porosity is also likely to translate into a reduction in
clinical sensitivity. Most reports of improvement in hypersensitivity are anecdotal;
however, fluoride and remineralization treatments are consistently recommended in
the literature, although a strong evidence base is lacking. There may be some addi-
tional benefit gained by prior deproteinization treatment; a similar finding has been
reported for fluorosed enamel [19, 22]. In both of these cases, this was achieved by
irrigation with a sodium hypochlorite solution (NaOCl); however, the clinical appli-
cability/practicalities need to be considered given the likely difficulties in achieving
adequate isolation and comfort. When NaOCl is used, the tooth needs to be com-
pletely isolated by sealed rubber dam, and as these teeth are often partially erupted,
this may be difficult to achieve as may be adequate local analgesia. The leakage of
the NaOCl into the oral cavity would have significant consequences.
Children with significant hypersensitivity or deemed at higher caries risk should
be prescribed an optimal-strength fluoride toothpaste under appropriate profes-
sional and parental supervision. Anecdotally, frequent use of stannous fluoride has
appeared to improve sensitivity in hypomineralized teeth; however, evidence is
lacking. For very young children where controlling fluoride ingestion may be diffi-
cult, a calcium phosphate-based product would be recommended initially in
Fig. 9.4 Polarized light

image of an MIH lesion
following exposure to a
CPP-ACFP solution in vitro
(in water, ×5 mag.).
Brown/orange area is the
unchanged lesion (>5 %
porosity), gray area (5 %
porosity) shows the part of
the lesion exposed to the
solution, while the red
surface coating protects the
unexposed (control) part of
the lesion
conjunction with professional application of a fluoride varnish or a stannous fluo-

ride gel. It seems likely that the greatest gains of continuing mineralization will be
made as the teeth emerge. Like demineralization lesions, hypomineralized enamel
defects have been shown to develop a thin but relatively well-mineralized surface
layer which helps prevent further loss of minerals but can inhibit subsequent, deeper
tissue improvement in mineral content (see Fig. 9.4) [6].
Surface Sealing
Sealants
In more severe hypomineralization cases, preventive measures alone are often insuf-
ficient and some form of surface protection is indicated [23]. At its simplest this will
be standard sealing and this is recommended prior to full emergence of the tooth
[24]. A glass ionomer cement (GIC) material is therefore the best initial choice as it
can tolerate the presence of some moisture and can provide a source of ions which
appear to be advantageous to the underlying tooth in several ways. An incidental
finding of an MIH characterization study suggested that deeper mineralization
improvements occur under a GIC sealant compared with enamel surfaces exposed to
the oral environment [25]. It has been reported that GIC materials also provide a
“halo protection” effect, whereby healthy enamel immediately adjacent to a GIC
material is less susceptible to demineralization, which may be further enhanced by
the addition of CPP-ACP to the GIC [26]. Where PEB has already occurred,
protective sealing may be extended over all the affected areas to decrease caries risk
until such time that more definitive treatment can be undertaken. Where sealing can-
not be achieved, full coverage options should be considered (Chaps. 10 and 11).
Once isolation can be established, there are more clinical options available (Chap.
11). However, resin-based sealants are not always recommended because of the dif-
ficulties in bonding to enamel that is hypomineralized and has a higher protein con-
tent (see Chap. 6). It is widely reported that enamel defects display atypical and often
poor etch patterns (Chap. 6) with implications for bonding of resin materials includ-
ing resin sealants [27–30]. Extended etching times for severely fluorotic enamel are
recommended because of the increased resistance of fluorapatite to acidic dissolution
[27]. There is some evidence to suggest that the higher organic content of defective
enamel limits remineralization and reduces bond strengths. Techniques such as irri-
gation with NaOCl can remove protein and improve bonding and penetration of resin
materials in MIH and AI [29, 31–33]. It appears important that to increase bond
strengths, the NaOCl should be used after etching, not before [29, 34, 35].
Methods reported to increase bond strengths and retention rates of resin-based
sealants to intact hypomineralized occlusal surfaces have involved the use of a
single-bottle adhesive system (One-Step®, Bisco, IL, USA) and pretreatment with
NaOCl after etching. Resin infiltration with materials such as Icon (DMG, Hamburg,
Germany) has been reported to increase bond strengths in vitro; however, whether
this decreases sensitivity and PEB is unknown [29, 34, 36].
Resin Infiltration
The recent development of a commercial resin infiltrant for treatment of carious

lesions has led to some preliminary studies to see if this low-viscosity TEGMA
resin can be used to seal and improve the physical qualities of hypomineralized
enamel. There is little published research; however, what exists indicates that while
the pattern of infiltration is hard to predict, it is possible to obtain resin penetration
close to the amelodentinal junction (ADJ) [36, 37]. Where infiltration was achieved
there was an increase in cross-sectional hardness of the enamel [36]. The effect of
pretreatment with NaOCl improved infiltration. However, further research is
required before this can be recommended as routine treatment [36]. There has also
been some initial in vitro research suggesting that the use of NaOCl after etching,
followed by a resin infiltrant prior to bonding, may increase bond strengths. The
pros and cons of the clinical applicability of this increased complexity and cost need
to be investigated and discussed.
Other Sealing Methods
In some children and adolescents, full coverage of affected teeth may be required in
a protective rather than reparative capacity [3]. This may be for two reasons – pro-
tection of friable structure and decreasing sensitivity. In the case of a generalized
defect such as AI, composite strip crowns on anterior teeth and preformed metal
crowns on posterior teeth (cemented with GIC) may be appropriate. This can be
definitive for the primary dentition and transitional for the permanent dentition
(Chaps. 10 and 11).
There has been some suggestion for the use of a technique modified after that of
Zagdwon et al. where preformed crowns are placed over severely hypomineralized
permanent molars with as little tooth preparation as possible [38]. This technique
often involves the of use orthodontic separators to create space for the crown, reduc-
ing the need for interproximal preparation. The minimal occlusal preparation does
cause an increase in vertical dimension. However, in children this spontaneously
decreases over the course of a couple of months. The pulpal status of the tooth needs
to be at a stage where any inflammatory changes present are reversible. This tech-
nique is similar to the “Hall technique” advocated recently for the treatment of ini-
tial lesions in primary teeth which relies on the sealing of the lesion from the oral
environment, thereby stopping progression of any caries and also protecting devel-
opmental weakened tooth structure [39]. While results for the Hall technique are
promising, further research is required in this area, particularly in the context of
developmental defects.
Summary
For hypoplastic defects, the provision of a cleansable surface is the most effective
way of decreasing caries risk – this may be achieved with resin composites or full
coverage. Sensitivity is less of an issue with these teeth, but if it is present, similar
techniques to those for hypomineralization defects are appropriate.
For hypomineralized defects, maintenance of the enamel surface integrity and
limitation of sensitivity are essential. Increase in caries risk due to the inability to
clean the hypomineralized area can lead to PEB. Therefore the conditions should be
seen as interrelated. Adherence to the modified recommendations according to
William et al. [40] and Oliver et al. [10] is appropriate (see Table 9.1).
Table 9.1 Clinical management tree for hypomineralized teeth

Steps Procedures
Hypomineralization risk Assess medical history for putative etiological factors
identification Establish caries risk and modify as necessary
Early diagnosis Examine at-risk molars as they erupt especially if permanent
incisors, second primary molars, or other teeth are affected.
Assess severity
Remineralization Apply topical fluoride and calcium-based products such as
CPP-ACP. Consider “adult strength” toothpaste. Minimize
caries risk
Desensitization Assess for remineralization. Protect porous lesions with GIC
or resin sealant. Decrease exposure to acidic drinks
Prevention of caries and PEB Assess for remineralization and desensitization. Consider
full coverage of tooth if at high potential for PEB
References
1. Rodd HD, Boissonade FP, Day PF. Pulpal status of hypomineralized permanent molars. Pediatr
Dent. 2007;29(6):514–20.
3. Weerheijm KL. Molar Incisor Hypomineralization (MIH): clinical presentation, aetiology and
management. Dent Updat. 2004;31(1):9–12.
4. Wang LJ, Tang R, Bonstein T, Bush P, Nancollas GH. Enamel demineralization in primary and
permanent teeth. J Dent Res. 2006;85(4):359–63.
5. Salanitri S, Seow WK. Developmental enamel defects in the primary dentition: aetiology and
clinical management. Aust Dent J. 2013;58(2):133–40.
6. Crombie F, Manton D, Palamara J, Zalizniak I, Cochrane N, Reynolds E. Characterisation of
developmentally hypomineralised human enamel. J Dent. 2013;41(7):611–8.
7. Wright JT. Amelogenesis imperfecta. Eur J Oral Sci. 2011;119 Suppl 1:338–41.
8. Elfrink MEC, ten Cate JM, van Ruijven LJ, Veerkamp JSJ. Mineral content in teeth with
Deciduous Molar Hypomineralisation (DMH). J Dent. 2013;41(11):974–8.
9. Featherstone JDB. Remineralization, the natural caries repair process – the need for new
approaches. Adv Dent Res. 2009;21(1):4–7.
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Restorative Management of Dental
Enamel Defects in the Primary Dentition 10
Monty Duggal and Hani Nazzal
Abstract
Many genetic and environmental conditions can interfere with the normal
development of primary teeth and can manifest as defects in the enamel.
Such defects can be associated with pain and discomfort and can have esthetic
implications which may affect the young child’s self-esteem. It is not only
important for clinicians to be able to diagnose the defects but also to under-
stand the implications these might have on restorative techniques and materi-
als they choose. Restorative management can be challenging because of the
limited cooperation in some children, the extent of the defects, and the sensi-
tivity that may be present. The main aims of treatment should be to alleviate
pain and sensitivity, improve esthetics, and manage any other concerns that
the child or the parents might have. This should be followed by consideration
of long-term treatment planning involving progression of the primary through
to the mixed dentition. In many cases, especially where there is a genetic
component with generalized involvement of both the primary and subsequent
permanent teeth, an interdisciplinary approach to management is appropri-
ate. Finally it is important to be able to provide treatment in a manner the
child finds acceptable. This chapter helps the reader identify and effectively
manage primary teeth with commonly encountered enamel defects.
M. Duggal, BDS, MDSc, PhD

Department of Paediatric Dentistry, School of Dentistry, University of Leeds,
Clarendon Way, Leeds, West Yorkshire LS29LU, UK
H. Nazzal, BDS, PhD (*)
Department of Paediatric Dentistry, School of Dentistry, University of Leeds,
Clarendon Way, Leeds, West Yorkshire WF1 4JN, UK

124 M. Duggal and H. Nazzal
Introduction
In this chapter the management of developmental defects of enamel (DDE) in chil-

dren is discussed, and the choice of techniques and materials, which are appropriate
in the growing child, is elaborated upon. An important consideration is that many
affected children will not have had any invasive dental treatment before. Suggested
strategies for managing young children are included.
Etiology of DDE in the Primary Dentition
The etiology of DDE in the primary dentition can be divided into systemic and
local causes. Local factors affecting primary teeth are limited to traumatic injuries.
This is occasionally seen following neonatal intubation or the use of an oral air-
way for an extended period of time [1]. However, this has to occur at a very young
age, i.e., before birth or during infancy, for it to affect enamel formation of the
anterior primary teeth, making this an unusual phenomenon. Systemic factors, on
the other hand, are more common and comprise a variety of conditions [2, 3]
which are summarized in Table 10.1 below and discussed in more detail in Chaps.
1, 2, 3, and 4.
Unlike genetically determined defects, the effect of developmental factors on
enamel formation depends upon the timing, duration, and severity of these factors
and is usually referred to as chronological hypoplasia/hypomineralization
(Fig. 10.1). For these factors to affect the formation of enamel in primary teeth, they
will occur during hard tissue formation of the primary teeth. This starts with central
incisor formation at 13–16 weeks after fertilization and ends with the second pri-
mary molars at 8–11 months of age [4]. The type of resulting defect will reflect
whether the insult occurred during enamel matrix formation (leading to hypopla-
sia), mineralization (causing hypocalcification defects), or during maturation phase
(causing hypomaturation defects). A clinician is likely to encounter two main types
of enamel defects: hypoplastic and hypomineralized enamel. Hypoplastic enamel
[4, 5] (Fig. 10.2) is caused by incomplete or defective formation of the organic
Table 10.1 Systemic factors that may be associated with DDE in primary teeth
Factors Examples
Genetically determined Amelogenesis imperfecta [3]
Chromosomal anomalies Down syndrome
Congenital defects Cardiac defects, unilateral facial hypoplasia or hypertrophy [2]
Inborn errors of Galactosemia, phenylketonuria, alkaptonuria, erythropoietic
metabolism porphyria, primary hyperoxaluria
Neonatal disturbances Prematurity, hypokalemia
Infectious diseases Measles, chickenpox
Neurological disturbances
Chronic medical diseases Hepatic disease, endocrinopathies, renal disease, enteropathies
Maternal health during Hypertension, nutritional deficiency, substance abuse
pregnancy
Nutritional deficiencies Vit. D deficiency
10 Restorative Management of Dental Enamel Defects in the Primary Dentition 125
Fig. 10.1 Chronological

hypoplasia affecting the
lower second primary molars
and chronological hypomin-
eralization affecting lower
first permanent molars
Fig. 10.2 (a–c) Preoperative

images of a 3-year-old child
with a hypoplastic form of
AI. Note the buildup of
calculus associated with the
lower primary molars
(Courtesy of Nicky
Kilpatrick)
enamel matrix by ameloblasts during tooth formation (secretory stage) resulting in

thinner but normally mineralized enamel. Hypomineralization occurs due to a fail-
ure in enamel matrix mineralization [4, 5]. This is further divided into hypocalcifi-
cation (defective mineralization) or hypomaturation (defective removal of proteins
from enamel matrix preventing maturation). Clinically, hypocalcified enamel is
usually yellow-brown in color with more potential for enamel breakdown, while
hypomature enamel may appear normal, mottled, or slightly opaque [4, 5].
Management of DDE in Primary Teeth
The management of enamel defects in generalized conditions or where they are

likely to affect the permanent dentition is challenging and usually requires immedi-
ate-, short- and long-term planning [6]. Patients with amelogenesis imperfecta (AI),
for instance, may have other associated anomalies such as disturbances in eruption,
anterior open bite, pulpal calcifications, pathological root or crown resorption,
and/ or taurodontism. These anomalies affect the long-term management and usu-
ally require an interdisciplinary approach starting in the later primary/early mixed
dentition. Patients with primary teeth defects often present at a young age and the
parents want immediate treatment to improve the child’s appearance. However, it is
important to make a treatment plan which will encompass a stepwise approach that
includes a short-, medium-, and a long-term treatment plan. Children with DDE
often require several interventions throughout their primary, mixed, and permanent
dentition stages [7], and should general anesthesia (GA) be required, it is crucial to
plan and provide the necessary management in a timely manner so that the least
number of GAs are required throughout the child’s life.
The aims of management, especially at the primary dentition stage, include:
1. Prevention and maintenance of good oral hygiene

2. Desensitization and pain management of affected teeth
3. Restorative management (esthetic management and stabilization of affected
teeth)
4. Behavior management to help children manage the dental care they need
Prevention
The gingival condition and oral hygiene of patients with both generalized defects,
such as in AI or isolated defects, are often poor. Figures 10.1 and 10.3 show the
presence of calculus in children with hypoplastic and hypomineralized AI. This
occurs because many of the teeth are sensitive to thermal and toothbrush stimuli,
which prohibits effective toothbrushing. Having enamel defects can also be an addi-
tional caries risk factor as the teeth are rough and porous with softer and/or thinner
enamel. Therefore, treatment planning should firstly focus on prevention including
effective oral hygiene instruction using warm water and very soft brushes,
Fig. 10.3 Anterior view of

the mixed dentition in a child
with AI showing poor oral
hygiene, calculus deposits,
and gingivitis
optimizing fluoride exposure both at home and with regular professional applica-
tion, diet advice and sealants, or temporary restorations where appropriate. A guide
is given in the UK Department of Health and British Association for the Study of
Community Dentistry toolkit [8]. Comprehensive dietary analysis and advice is
essential from both a caries and tooth surface-loss perspective. This will involve
identifying fermentable carbohydrates and acidic foods and beverages in the diet
and advising on their reduction and timing of use to minimize damage.
It is unrealistic to expect children with DDE to dramatically improve their oral
hygiene without some intervention to reduce the sensitivity of the teeth. This might
include the use of preventive agents such as topical fluorides or calcium phosphate-
containing products or by placing interim restorations (glass ionomer cements or
compomers) that will seal the dentine, thereby allowing the child to brush the
affected teeth with less discomfort. In younger children, below 6 years-of-age, par-
ents should help with brushing twice daily and should carry out regular flossing if
the contact areas are closed.
Reducing Sensitivity
Several strategies are available for the treatment of the sensitivity associated with
DDE, although none have been found to be reliable for every case (see Chap. 9). It is
important to consider desensitization in order to reduce the discomfort felt by many
children with DDE. This sensitivity also makes restorative interventions, especially
with adhesive materials, even more challenging. Some of the suggested methods for
desensitization include the use of topical fluoride preparations, in particular fluoride
varnishes, such as Duraphat® 22,600 ppm F (Colgate Oral Care) or 3M Espe Fluoride
Varnish with tricalcium phosphate. Care should be taken to use the recommended
amounts on erupting teeth with DDE in preschool-aged children. More recently a
combination of casein phosphopeptide and amorphous calcium phosphate
(CPP-ACP – GC Tooth Mousse/MI Paste) with and without fluoride has also been
advocated to help decrease sensitivity. CPP-ACP helps create, stabilize, and deposit a
supersaturated solution of calcium and phosphate at the enamel surface. Therefore, it
has been suggested that home application of a CPP-ACP-containing cream especially
when combined with fluoride use will help remineralize and desensitize by acting as
a source of bioavailable calcium and phosphate. Other topical fluorides may also be
useful; among these are stannous fluoride gels, such as Gel-Kam® 1,000 ppm F
(Colgate Oral Care) or OMNI Gel 0.4 %/1,000 ppm F (3M). There has also been a
suggestion that desensitizing toothpastes may help with some hypomineralized teeth.
Currently there is no strong evidence to support the efficacy of these strategies in the
management of DDE, though all these products may help reduce sensitivity and
enhance mineralization of the hypomineralized areas. However, none of the available
products are always effective, and clinicians should consider using products in com-
bination or trying different products in an attempt to alleviate the symptoms in patients.
Pain and Anxiety Management
Pain management in children is an integral part of good pediatric dentistry. Both the
technique and choice of local analgesia are important for the provision of high qual-
ity, effective restorations in children, particularly if they are to last for the lifetime
of the primary teeth (up to 8 years). In particular, teeth that have DDE are more
likely to be sensitive and consequently providing effective analgesia is often more
difficult than for unaffected teeth.
Behavior Management
Clinicians should evaluate the understanding and coping skills of the child with
DDE when the teeth require intervention. One of the commonly encountered prob-
lems is that children with DDE present with higher levels of anxiety. This is espe-
cially true in cases where the defect is associated with sensitivity or where previous
treatment has been attempted without appropriate pain control or behavior manage-
ment. If such defects are suspected, especially when associated with sensitivity, it is
important not to air-dry these teeth during examination but to dry them gently with
a cotton pellet. Managing young children requires empathy and some knowledge of
behavior management techniques for children. Many pediatric dentistry textbooks
cover useful techniques for helping children cope with restorative care. In the center
of all the techniques is “tell, show, and do” which will allow most children to be able
to cooperate for restorative care when it is presented in age-appropriate language
and demonstration. This of course takes a little extra time but is time well spent in
preparing a child for more complex care as they grow older.
Local Analgesia
For children who have been sensitized to previous invasive dental treatment, in particu-
lar local analgesia, the use of computer-controlled anesthesia (such as the Wand and the
Wand STA – controlled dental anesthesia, Dental Practice Systems, Welwyn, Herts,
UK) can be an excellent way to administer local analgesia. The Wand provides several
advantages over conventional syringes including the fact that it does not look like a
conventional syringe; the fine bevel of the needle and the slow speed with which the
local analgesic solution can be administered make it a simple way to deliver painless
local analgesia. The use of 4 % articaine should be considered in managing older chil-
dren especially where there is a history of failed local analgesia. For children over
4 years-of-age who are extremely wary of local analgesia, infiltration with 4 % artic-
aine in the lower arch as opposed to an inferior dental block may provide adequate
analgesia for restorations to be placed [9]. It is also important to make use of topical
anesthesia. The preemptive use of systemic analgesics (in accordance with local guide-
lines) can also be an effective way of helping children cope with care successfully [10].
Sedation
In extremely apprehensive children who are otherwise cooperative, the use of inha-
lation sedation should be considered. This form of sedation has the particular ben-
efit of having an analgesic effect which lessens the child’s response to painful
stimuli. Hence for children whose apprehension is due to sensitive teeth that have
been previously treated without effective local analgesia, inhalation sedation with
nitrous oxide and oxygen provides a safe, effective, and noninvasive method for
managing the child’s anxiety [11]. Other forms of sedation can be utilized according
to local guidelines and clinicians’ usual practice.
General Anesthesia
Clinicians treating children with severe enamel defects should consider the early use
of general anesthesia to allow effective successful stabilization of the primary teeth.
Previous studies of treatment under general anesthesia have shown good outcomes
with decrease in the numbers of repeat restorations [12]. Children with severe enamel
defects often present before they are old enough to cope with restorative dentistry;
therefore, the use of general anesthesia is effective and valid for this group.
Restorative Management of DDE in the Primary Dentition
The decision to provide restorative management of enamel defects in primary teeth

depends on several factors:
1. Type of enamel defect. AI is a generalized condition affecting the entire crown

in addition to often being more severe than other developmental defects. The
type of AI will also affect the type of restoration provided. Where there is miss-
ing enamel or enamel loss after eruption, full-coverage restorations should be
considered early in the planning.
2. Extent and severity of the defects. In some cases of chronological hypoplasia,

children may have few if any symptoms or significant tooth surface loss, which
will suggest that less radical restorative options can be considered.
3. Associated symptoms. In cases of severe sensitivity, full coverage should be
considered.
4. Esthetics with possible psychological effects on the child. The psychological
impact of these conditions in children should never be underestimated (see
Chap. 7). Esthetic management should be offered as soon as the child and the
parents wish to have this carried out.
5. Patient cooperation and the method of treatment. In children who cannot cope
with treatment under local analgesia, alternative strategies such as sedation or
general anesthesia should be considered [7].
Interim Restorations
In some cases it may be appropriate to place interim therapeutic restorations to

immediately alleviate pain and sensitivity while awaiting more definitive restorative
treatment. The provision of these interim restorations also allows the clinician to
establish rapport with the child and assist in behavior management. Materials such as
resin-modified glass ionomer can be useful as these materials incorporate appropri-
ate bonding for both enamel and any exposed dentin (Fig. 10.4) [13]. Some of the
materials also incorporate a color that allows good visualization of the extent of the
restoration on the tooth surface, e.g., Fuji VII/Triage (GC Corporation). The release
of fluoride from these materials, although not proven to be a major factor, may also
help to reduce sensitivity by encouraging further mineralization of the surrounding
enamel. Compomer materials (polyacid-modified composite) might also be consid-
ered and can be placed using self-etching primers. These materials have the advan-
tage of being more wear resistant than glass ionomer cement-based materials and
have dual-bonding technology, which may seal both enamel and dentin effectively
especially when further sealed with adhesive resin or fissure sealant following place-
ment [13].
Longer-Term Restorations of Molar Teeth
Composite Resin Restorations
Composite resin should be considered in cases where:
• The defect is demarcated to a defined area, no more than two surfaces

• Cusp tips are not involved
• There is no significant sensitivity
• Margins of the defect are supragingival
Fig. 10.4 (a, b) Example of

the use of a glass ionomer
cement used for interim
protection on hypoplastic
second primary molars in a
3-year-old (Courtesy of
Nicky Kilpatrick)
There is evidence to suggest that hypomineralized enamel does not always show
a typical etch pattern compared with normal enamel. This can potentially reduce the
strength and integrity bond of enamel to composite resin [14, 15]. This is less of an
issue with mild cases where normal enamel is present around isolated lesions.
Pretreatment with 5 % sodium hypochlorite has been advocated to improve bond
strength to hypocalcified enamel [16, 17]. The removal of affected enamel and
bonding to dentin, which may be sclerotic, has also been suggested. However
research outcomes are still not clear on the most reliable approach to bonding to
sclerotic dentine in primary teeth. Recent research would suggest that reduced etch-
ing times may result in more reliable bonding particularly when using a total-etch
system [18]. Clinicians may need to try different approaches to achieve good results
and reviewing research on the particular bonding system being used when planning
treatment can be very helpful.
Preformed Crowns
Full coverage with either stainless steel or other esthetic preformed crowns should
be considered in cases where:
• The defect involves multiple surfaces.

• There is significant sensitivity.
• Margins of defects are subgingival.
• There is involvement of the cusp tips in posterior teeth.
• Enamel is prone to “chipping,” especially in some cases of AI.
• Treatment has to be carried out under general anesthesia and the child is unlikely
to manage restorative care in the immediate future.
While preformed metal crowns (stainless steel crowns) are a well-recognized

option for the treatment of carious primary molars, they also have an important role
in the management of DDE-affected primary molars [19] (Figs. 10.3, 10.5, 10.6,
and 10.7). Figures 10.3 and 10.5 illustrate good occlusal support provided by stain-
less steel crowns. The placement of stainless steel crowns requires minimal tooth
preparation. They are less bulky than the white preformed crowns that may suffer
wear and chipping of the veneer (Fig. 10.8). More recently for very young children,
a technique, known as the “Hall Technique,” has been described in which stainless
steel crowns are placed with no preparation (Fig. 10.7) [20]. While this technique is
promoted for children presenting with dental caries, anecdotal reports suggest that
using this technique to place stainless steel crowns over hypomineralized or hypo-
plastic primary second molars soon after they erupt is a successful way of managing
these teeth. Furthermore adopting this technique means that young children can be
treated, without resorting to general anesthesia, early in the dental chair without
local analgesia. Long-term studies of the use of stainless steel crowns for carious
teeth would suggest that crowns placed over teeth with DDE have advantages over
other restorative materials [21]:
1. Perform better where more than two surfaces are affected.

2. Less tooth removal is required.
3. Failure rate is much less than other restorative materials.
4. Moisture control is less critical than when restoring with other materials.
5. Placement is less time consuming than resin restorations.
6. Are more cost effective as shown by the outcomes over time.
Fig. 10.5 (a–c) Intraoral

images of same child in
Fig. 10.1 with hypoplastic
AI, 2 years post-
comprehensive restorative
care under general anesthetic.
Note the significant
improvement in gingival
health brought about by
reduction in sensitivity
(Courtesy of Nicky
Kilpatrick)
Longer-Term Restorations of Anterior Teeth
Composite restorations are appropriate when restoring anterior teeth with demarcated
defects affecting a maximum of two surfaces. Where lesions are diffuse, are large,
involve multiple surfaces, or are associated with sensitivity, the use of strip crowns or
preformed crowns is advocated [22, 23]. The technique for placing strip crowns
involves the removal of approximately 1–2 mm of enamel from all the surfaces of the
crown. The enamel is etched and prepared for bonding according to the manufactur-
er’s instructions and the crown is filled with composite, placed on the tooth, with
excess removed from the margins and the composite cured. Once the strip crown has
Fig. 10.6 (a) Preoperative

photograph of child with
hypomaturation-hypoplasia
AI. (b) Postoperative
photograph showing
restoration of the hypoplastic
second primary molars using
stainless steel crowns. The
anterior teeth were mildly
affected, asymptomatic, and
esthetically acceptable,
therefore were managed with
preventive care
Fig. 10.7 (a–c) Same child as in Fig. 10.4 post-placement of stainless steel crowns on second
primary molars using the Hall technique (Courtesy of Nicky Kilpatrick)
Fig. 10.8 Occlusal view

showing restoration of the
lower right second primary
molar with NuSmile
Signature white crown in
which the veneer has chipped
but the crown remains intact
Fig. 10.9 Occlusal view of

anterior strip crowns and
stainless steel crowns placed
in a child with AI (Courtesy
of Nicky Kilpatrick)
been removed, the restoration is finished in the usual manner (Figs. 10.5c and 10.9).
More recently, the use of preformed white veneered crowns such as NuSmile Signature
and pre-veneered Kinder Krowns® or zirconia crowns such as NuSmile zirconia and
Zirconia Anterior Kinder Krowns® is advocated by some clinicians. These crowns
provide very good esthetic results (Fig. 10.10). However they do require more exten-
sive crown preparation and care must be taken to protect the pulp. The preformed
crowns do have a higher cost and chipping can occur in the veneered stainless steel
crowns (Fig. 10.8). Further studies are needed to assess the longevity of these restora-
tions with particular attention being paid to their cost-effectiveness.
Extraction of Primary Teeth with DDE
In some cases extractions of severely affected teeth may be required. This should be
done with evaluation of the space requirements in the developing dentition. In chil-
dren where multiple teeth are affected and extractions are required, an
Fig. 10.10 Anterior primary

incisors with zirconia crowns
in a 2-year-old child
(Courtesy of Bernadette
Drummond)
interdisciplinary approach involving an orthodontist should be considered to opti-

mize the development of the permanent dentition occlusion. Wherever possible,
preventive and restorative approaches should be the preferred option as this always
gives the child and their family a positive dental health message, where preservation
of teeth is considered important. For further discussion regarding the interdisciplin-
ary treatment planning needed for these children, see Chap. 8.
Summary
Children who suffer from DDE in their primary dentition deserve the highest qual-
ity restorative and preventive treatment. These children can be young, extremely
apprehensive, and often caries-free, which means that management of affected teeth
may be their first experience of invasive dentistry. Treatment should be provided
with the use of appropriate behavior management techniques and analgesia to help
children develop skills to cope with the restorative care both immediately and into
their future.
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Restorative Management of Permanent
Teeth Enamel Defects in Children 11
and Adolescents
Suzanne M. Hanlin, Lucy A.L. Burbridge,

and Bernadette K. Drummond
Abstract
The clinical challenges associated with the restorative management of develop-
mental defects of enamel (DDE) have been well documented and include man-
aging sensitivity and caries risk, loss of occlusal determinants, and the negative
impact on individual self-worth and social interaction. This chapter outlines
management options for DDE associated with molar incisor hypomineraliza-
tion (MIH), amelogenesis imperfecta (AI), fluorosis, and intrinsic discoloration
in permanent teeth. Many materials and techniques may be used to manage
DDE. The complexity of intervention is dictated by the severity and nature of
the disturbances including color (brown/cream/yellow/white opacities – hypo-
mineralization), structure (hypoplasia – pits, grooves), pre-eruptive resorption,
post-eruptive breakdown, the patient’s individual circumstances, and the age and
stage of development.
S.M. Hanlin, BDS, MDS, GradDipHealInf

Department of Oral Rehabilitation, Faculty of Dentistry, University of Otago, PO Box 647,
9054 Dunedin, New Zealand
L.A.L. Burbridge, BDS DipConSed, MClinDent
Paediatric Dental Department, Newcastle Dental Hospital,
Newcastle Upon Tyne NE2 4AZ, UK

140 S.M. Hanlin et al.
Introduction
The aim of treatment for a child or adolescent with developmental defects of enamel
(DDE) is to provide comfort, natural form, and function and prevent additional
problems. Setting achievable goals is key to ensuring a successful outcome because
the impact on perception of attractiveness and well-being can sometimes skew and
heighten the expectations of children and families unrealistically [1]. Management
and maintenance costs can be considerable and impact directly and indirectly on all
members of a family. Extensive defects may be associated with other anomalies and
the development of an interdisciplinary plan in early childhood is important to pro-
tect compromised tooth structure and establish occlusal stability [2]. Definitive
management may not occur until late adolescence or early adulthood, and consider-
ation must be given to the ability of children to manage treatment and avoid burn-
out. Clinicians must be responsive to the changing esthetic and functional needs of
the developing child and adolescent.
Restorative modalities can include tooth bleaching and microabrasion therapy,
enamel infiltration with composite resin [3], direct and indirect veneering materials
and/or indirect (laboratory-fabricated or computer-aided design, CAD-milled)
polymethyl methacrylate (PMMA), and composite or ceramic restorations. Full-
coverage restorations may be required for more severely affected teeth where mask-
ing of the underlying tooth color is required, or there is severe sensitivity or a need
to improve the shape of the tooth. Preformed stainless steel crowns (SSC) can be
placed on affected permanent (as well as primary) molar teeth in childhood to main-
tain occlusal support and arch length [4]. The use of composite, acrylic, or polycar-
bonate shell crowns has also been reported [5, 6]. In late adolescence or early
adulthood, these interim solutions may be replaced with laboratory-fabricated com-
posite resin, ceramic, porcelain fused to metal (PFM), cast, or CAD-milled ceramic
or alloy crowns.
Choosing Materials and Techniques for Bonding

in Compromised Enamel
Because of the wide variation in the clinical presentation of enamel defects, recog-
nition of the etiology and subsequent management can be difficult. However, dif-
ferential diagnosis of the defect will assist in determining which treatment
techniques and materials may perform best. It has been suggested that by under-
standing the origin of the enamel defect, clinicians are able to more appropriately
target the treatment to the patient’s needs, preserve residual tooth structure, and
avoid overly invasive procedures [7]. Conventional enamel etching and bonding
techniques following manufacturer’s guidelines are usually successful for enamel
that is reduced in quantity but still well mineralized (i.e., thin or hypoplastic). If
dentine is relatively unaffected, dentine bonding systems, glass ionomer, polyacid-
modified composite resins (PMCR), or resin-modified glass ionomer cements
11 Restorative Management of Permanent Teeth Enamel Defects 141
(RMGIC) offer predictable bond strengths to dentine and improve restoration

prognosis. Hypomineralized enamel and/or a defective dentinoenamel junction
(DEJ) affects the restoration bond strength, and the enamel may shear off or detach.
Hypocalcified enamel often results in increased wear rates and chipping.
Hypomineralized enamel (containing more protein) exhibits significantly lower
micro-shear bond strengths with predominantly cohesive fractures of restorations
and enamel loss due to shallow etching patterns, a porous adhesive interface, and
cracks in the enamel [8].
Approaches that have been investigated to improve bonding to defective enamel
include modification of the acid used for etching (organic rather than inorganic), use
of self-etching primers, glass ionomer cement sandwiches with composite, resin-
modified glass ionomer cements (RMGIC), and pretreatment of enamel with 5 %
sodium hypochlorite [9–15]. However to date, none of these approaches provide a
predictable way of achieving adhesion to hypomineralized enamel. This remains a
challenge for long-term restoration success and is probably the single most impor-
tant factor that forces progression to full-coverage restorations in late adolescence
or early adulthood.
Management of Enamel Defects in Anterior Teeth
Treatment of anterior teeth with enamel defects is usually initiated by patients

because of dissatisfaction with their appearance. Improvement is important for psy-
chosocial well-being particularly during the mixed and early permanent dentitions
[16, 17] (See Chap. 7). During childhood, the least invasive approach necessary to
meet the esthetic demands of each individual should be adopted. For every tech-
nique, pretreatment radiographs and tooth shades should be recorded at baseline
against which changes can be assessed over the long term.
Microabrasion
Acid pumice microabrasion is a controlled method of removing surface enamel to

reduce discolorations particularly when this is limited to superficial layers and to
allow further mineralization. Microabrasion is achieved by a combination of abra-
sion and erosion (“abrosion”) [18]. Approximately 100 μm of enamel is removed in
one or two appointments. Any additional enamel removal has the potential to dam-
age the pulp or can result in exposure of underlying dentine [19].
Indications
• Diffuse (superficial) and small demarcated enamel opacities
• Hypomineralized enamel defects
• Post-orthodontic treatment decalcification
• Initial treatment for demarcated enamel opacities
Contraindications
• Deep hypoplastic enamel defects
• Intrinsic discolorations, e.g., tetracycline (dentinal) discoloration
• Discoloration associated with nonvital teeth
Technique
• Clean teeth with pumice and water to remove superficial staining and plaque and
expose a clean enamel surface, wash, and dry.
• Isolate the teeth with dental dam. Mix 18 % hydrochloric acid (HCl) with pumice
into a slurry or use acid from a proprietary kit. Apply a small amount to the labial
surfaces using a rubber cup rotating slowly (5–10 s). Wash carefully into an aspi-
rator tip. Repeat until the stain has reduced, up to a maximum of 60-s acid expo-
sure. Remove the dam and apply color-free neutral fluoride.
• The patient should apply either fluoride gel- or a calcium-based material (CCP–
ACP, calcium triphosphate) several times a day until follow-up to enhance
remineralization.
• Review 2–4 weeks later, repeat once more if clinically indicated, and if not, con-
sider an alternative treatment modality. Repeat sensibility tests and update
photographs.
Outcome
It is important to give detailed preoperative explanation to establish realistic expec-

tations. Delay final review for at least 1 month as the appearance of the teeth will
continue to improve over this time [20]. The best outcomes are achieved in cases of
brown mottling that are more easily masked than more opaque white lesions and
even white mottling becomes less perceptible (Fig. 11.1a, b). Improvement has been
attributed to the relatively prismless layer of compacted surface enamel produced
by the “abrosion” technique which alters the optical properties of the tooth surface
[18]. No associations between microabrasion and pulpal damage, increased caries
susceptibility, or prolonged thermal sensitivity have been reported. The technique is
straightforward and not time-consuming to perform for the operator or patient.
Microabrasion may assist with masking of a lesion in preparation for later compos-
ite restorations or veneers. This technique can be used in conjunction with bleach-
ing agents with good outcomes [21] and can reduce the impact of the yellow hue or
lighten other staining further [22, 23].
Bleaching
A bleaching agent (e.g., 10 % carbamide peroxide) can be applied to the surfaces of

teeth with the aim being to lighten color. The exact mechanism of bleaching is
unknown, but the release of hydrogen peroxide anions, reactive oxygen molecules,
and free radicals is thought to be involved in lightening the stained mineral and
Fig. 11.1 (a, b) Change in

enamel on permanent upper
incisors following two
microabrasion treatments
with ongoing use of
CPP-ACP with fluoride
protein in the enamel. Discoloration can reoccur because of a combination of chem-

ical reduction of the previously formed oxidation products, marginal leakage of
restorations allowing ingress of bacterial and chemical by-products, salivary or tis-
sue fluid contamination, or food color contamination via the permeable tooth
structure.
Indications
• Hypomineralized enamel defects
• Mild tetracycline staining
• Mild fluorosis
Contraindications
• Hypoplastic enamel defects
Techniques
• Vital bleaching can occur chairside/in the office or at home using custom-
designed bleaching trays (vacuum formed).
• The in-office technique involves application of carbamide peroxide to the sur-
faces of the teeth with activation of the process by a heat source. This consumes
chair time, adding to the expense. It is useful for treatment of mild enamel defects
where strict isolation of a single tooth is required.
• The home bleaching technique utilizes a custom bleaching tray constructed for
the maxillary and/or the mandibular teeth. The patient applies the carbamide
peroxide (gel) to the teeth via the tray on a daily basis until the desired color
change is achieved. There are many proprietary products available, and the prin-
cipal differences lie in the concentration of carbamide peroxide employed and
the amount of hydrogen peroxide released. Current recommendations indicate
that a 10 % solution is both safe and successful in modifying tooth color.
• The concurrent use of a calcium-based product such as that with casein phospho-
peptide–amorphous calcium phosphate will control any tooth sensitivity.
• Review 2–6 weeks later. An 80 % color change should have occurred.
• Take postoperative photographs including the pre- and posttreatment shade tab
for long-term records.
Outcome
Minor ulceration or irritation may occur during the initial treatment which may
relate to tray overextension. There may be transient pulpal sensitivity because carb-
amide peroxide gel (10 %) breaks down in the mouth into 3 % hydrogen peroxide
and 7 % urea. Both have low molecular weights that allow them to diffuse through
enamel and dentine and cause pulp irritation [24]. If sensitivity occurs, exposure
time can be decreased, or it may be necessary to discontinue treatment. To date,
there is no evidence that bleaching solutions with a low pH (below the critical pH of
5.2–5.8) causes enamel demineralization [25], possibly because urea, followed by
ammonia and carbon dioxide, is released on degradation of the carbamide peroxide
elevating the pH. Bond strength of composite resin to bleached enamel decreases
initially and has been attributed to the residual oxygen in the bleached tooth surface
inhibiting polymerization of the composite resin, but this returns to normal within
7 days [26]. Vital-bleaching systems do not modify the color of restorative materials
and any perceived effect is probably due to superficial cleansing. Regular retreat-
ment may be necessary to maintain effective lightening [27]. When considering the
use of bleaching products, the clinicians should be mindful of local regulations and
seek advice with respect to contemporary legislation.
Direct Restoration with Composite Resin
Composite resin bonded to etched enamel and/or pretreated dentine can be used to
restore tooth defects or improve esthetics by replacing or masking areas of discol-
ored or defective enamel.
Indications
• Demarcated enamel opacities
• Hypoplastic enamel defects
Contraindications
• Diffuse enamel opacities
Technique
• Apply dental dam and contoured matrix strips if required.
• Selective removal of demarcated lesion with a round diamond bur may be
required to optimize esthetics and bonding; however, bonding can also be
improved by selective use of GIC, or polyacid-modified composite.
• The enamel margins can be chamfered with a diamond fissure bur to increase the
surface area for retention and blend the composite margin with the enamel.
• Etch the area, wash and dry, and apply the primer, bonding agent, and the chosen
shade of composite. A brush lubricated with bonding agent can be used to smooth
and shape before light curing.
• Remove the matrix strip/dam, polish with graded polishing discs and diamond
finishing burs, and characterize the surface if required.
• Take postoperative photographs for records.
Outcomes
Restoration of localized hypomineralized or hypoplastic defects using composite

resin is not usually associated with sensitivity and may not need local anesthesia
unless there is caries with extension into dentine. These very conservative resin-
bonded restorations are particularly suited to newly erupted incisors (Fig. 11.2a, b).
Fig. 11.2 (a, b) Lesion on

the lower right lateral incisor
masked with composite resin
However, when it is not possible or desirable to remove the entire opacity, problems
with marginal staining, color matching, and suboptimal esthetics can arise.
Composite Resin Veneers
Composite resin can be used as a veneer to cover the entire labial aspect of the tooth
and improve color and contour. These veneers can also protect against further
breakdown of severely hypoplastic enamel as shown in Fig. 11.3a, b. Composite
veneers may be directly placed at the chairside or indirectly fabricated in the labora-
tory. Composite veneering is conservative, cost-effective, and repairable in the
mouth and may offer a satisfactory long-term alternative to full-coverage restoration
in mild enamel defects even in adults. They are useful in the young dentition, in
immature teeth with large pulp horns, large pulp chambers, immature gingival con-
tour, and short crown height on teeth that are still erupting.
Before proceeding with any veneering technique, it is necessary to decide
whether to reduce the thickness of labial enamel. Increased labio-palatal bulk with-
out tooth preparation makes it harder to maintain good oral hygiene. However,
increase in the labial contour may enhance appearance of in-standing or rotated
Fig. 11.3 (a, b) Resin

veneers for upper incisors in
the early mixed dentition
period
teeth. Bond strengths to enamel are increased when 200–300 μm of the surface
enamel is removed, and the restoration will maintain the tooth contour. Some reduc-
tion and/or use of an opaquing agent may be required to mask intense stain in a
discolored tooth. Hybrid composite resins finished to a higher surface luster can
replace relatively large amounts of missing tooth tissue or may be used in thin sec-
tions. Layering of dentine and enamel shades can be used to simulate natural color
gradations and hues.
Indications
• Large demarcated enamel opacities
• Widespread hypoplastic enamel defects
Contraindications
• Very darkly discolored teeth
• Minimal enamel defects
• Insufficient tooth tissue available for bonding
• Oral habits, e.g., woodwind musicians where embrasure may be critical
• Heavy occlusal load/parafunction
Technique: Direct Composite Veneers

• Use a tapered diamond or sharp tungsten carbide bur to reduce labial enamel by
0.3–0.5 mm if required. Identify a finish line at the gingival margin and extend
mesially and distally just labial to the contact points.
• Clean with a slurry of pumice in water, wash, and dry to remove plaque and
debris.
• Isolate the tooth with dam and a contoured matrix strip if needed.
• Etch enamel, wash, and dry. Apply a thin layer of primer and bond with a brush
and use an opaquing agent at this stage if discoloration is intense.
• Apply composite resin and shape. Light cure according to manufacturer’s
instructions at the gingival margin and the mesio-incisal, disto-incisal, and pala-
tal aspects if incisal coverage has been used. Different shades can be combined
to achieve matches with adjacent teeth and transition from a relatively darker
gingival area to a lighter more translucent incisal region.
• Finish the margins with diamond finishing burs and interproximal strips and the
labial surface with graded finishing discs.
• Take postoperative photographs for records.
Outcome
Good esthetics can be maintained for many years with regular reviews and repolish-
ing as needed [28]. Indirect composite veneers can be fabricated from elastomeric
impressions of the teeth, direct scanning of the prepared tooth or indirect scanning
of a stone working cast. Laboratory-fabricated composite veneers can provide many
of the characteristics of a ceramic veneer as described below. Color reproduction
and surface wear are improving. However, in a situation with high esthetic demand,
porcelain would still be the material of choice for restoration longevity and
stability.
Porcelain Veneers
Porcelain has superior esthetic properties to composite resin, improved resistance to

abrasion, and is well tolerated by gingival tissues. However, porcelain requires tooth
preparation to maximize fit and maintain tooth contour and to allow replication of
color. Disadvantages are that it is not repairable in the mouth and the laboratory
stages add to cost when compared to directly placed restorations. Best outcomes are
obtained after teeth have erupted completely, and therefore these restorations should
generally be delayed until late adolescence (ideally after 20 years of age). Further
information about preparation and design are covered in prosthodontic textbooks.
Restorative Management of Enamel Defects in Posterior Teeth
Clinicians face challenges when attempting to cover posterior teeth that are partially
erupted, have significant sensitivity, suffer post-eruptive breakdown, or are difficult
to anesthetize. Recommendations for managing sensitivity are included in Chap. 9.
Where it is not appropriate to seal enamel because of the degree of hypomineraliza-
tion, longer-term solutions are required.
Planning and Trialing the Occlusal Scheme
Patients with isolated teeth affected by enamel defects may have stable intra- (tooth
to tooth) and inter-arch (maxilla to mandible) contacts, and acceptable arch align-
ment and length that provide a functional occlusion. Restorative management can be
undertaken while conforming to the existing occlusal scheme. Where there is signifi-
cant hypoplasia of the occlusal surfaces of molars and premolars, the teeth may not
erupt into contact or the occlusal contacts that are formed may be on unstable inclined
planes that predispose to tooth movement and tooth chipping. Specific malocclusions
are associated with some types of AI including anterior open bite, delayed eruption,
and/or missing teeth [29]. In such cases, a reorganized occlusal scheme has to be
planned, and the vertical dimension, tooth replacement and repositioning, restorative
materials, and techniques all have to be taken in to consideration in order to achieve
long-term occlusal stability. Creation of the final occlusal interface requires a restor-
ative solution, but arch alignment, uncovering teeth and preservation of arch length,
requires orthodontic and sometimes surgical management to support the restorative
plan. Compromises in the ideal plan may often occur with successful management
requiring ongoing explanation and discussion with patients and parents.
Where enamel defects are minimal and the teeth have areas of normal enamel,
composite resin may be placed on the occlusal surfaces taking care to overlap the
bonded margins onto healthy enamel. Preformed stainless steel crowns placed over
the tooth with minimal or no preparation provide a very useful intermediate option
in the younger child. Before the permanent dentition has erupted, children usually
manage well if “bite opening” occurs when crowns are placed. However, care
should be taken when there is an existing anterior open bite. In adolescents, other
options such as PMMA resin crowns or Zirconia-milled crowns are being trialed
where esthetics may be of particular concern.
Stainless Steel Crowns
Stainless steel crowns have proved to be a very successful solution to pre-

serve posterior molars with developmental defects or other defects during child-
hood and adolescence until an appropriate time to place more permanent
restorations.
Indications
• Hypomineralized molars with breakdown or sensitivity
• Hypoplastic molars
• To prevent further tooth wear
Contraindications
• Severely broken down tooth that cannot retain the crown.
• Extraction and orthodontic management is preferred.
Technique with Tooth Preparation

• Provide local anesthesia and systemic analgesia if required for very sensitive
teeth.
• Minimally reduce the mesial, distal, and occlusal surfaces with a fine tapered
diamond
• Select and fit the appropriate crown. The crown height may need to be reduced,
crimped, and polished to place the margin just at the gingival margin of the
tooth [30].
• Check the occlusion, remove the crown, fill with a GIC-based cement, and
replace other tooth. Have the patient bite on gauze to seat the crown firmly.
Remove excess cement. Interproximal cement can be removed with floss with
several knots that is pulled through under the contact point.
Technique with No Tooth Preparation

• If possible, place orthodontic separating elastics a few days before treatment.
• Select the appropriate crown and adjust the height if required. Crimp the crown
and seat to check the margin.
• Check the occlusion, remove the crown, fill with an appropriate cement, and
replace on the tooth. Have the patient bite on gauze to seat the crown firmly.
Remove excess cement. Interproximal cement can be removed with floss with
several knots pulled through under the contact point.
a b
Fig. 11.4 (a) Radiographic appearance of appearance of a stainless steel crown on a lower left
first molar with DDE. (b, c) Stainless steel crowns placed on severely hypoplastic molars in
AI. Note the hypoplasia of the rest of the erupting permanent teeth
Outcome
Stainless steel crowns seal the teeth and provide thermal protection allowing the
pulps to mature. The enamel is protected from breakdown, the occlusion is main-
tained, and the teeth can continue to erupt to the mature height, thus providing
optimal conditions for more definitive solutions in late adolescence or adulthood
[4]. This is illustrated in Fig. 11.4a–c.
Periodontal Management: Gingival Recontouring and Crown

Lengthening
Adolescents with gingival enlargement, delayed or failed eruption of teeth or

impacted teeth, and missing teeth may require surgical intervention such as gingival
recontouring, crown lengthening, or surgical exposure prior to restoration. These
can be done using traditional surgical approaches and/or with soft tissue laser sur-
gery which is associated with improved tissue healing and reduced postoperative
discomfort [31]. Figure 11.5a–c demonstrates the increase in available enamel that
can be created following gingival recontouring in an adolescent with hypoplastic
Fig. 11.5 (a–c) Post crown lengthening surgery in maxillary and mandibular right and left quad-
rants showing access to good quality enamel in hypoplastic AI
AI. The extent of the defects and number of teeth will determine if periodontal man-
agement can be undertaken with local anesthetic alone or will require sedation or
general anesthesia. A team approach involving a pediatric dentist, prosthodontist,
periodontist, and orthodontist is important to optimize care. Good explanation of
the short- and long-term goals will help children and their parents understand the
reasons for surgery and the restorative plan.
Indirect Interim Restorations
Laboratory-fabricated composite resin (CR) crowns, CAD-milled PMMA, or CR

provisional crowns constructed from scans of the dentition may be resilient interim
restorations during adolescence. Premolar teeth can also be restored with directly or
indirectly fabricated composite onlay restorations or with complete coronal recon-
touring determined by the extent of the enamel defects. Pretreatment diagnostic
wax-up of the desired tooth form and contacts is useful in planning for this. Teeth
affected by AI may have a rim of less affected enamel at or just below the gingival
cuff, and once uncovered this provides a satisfactory finish line, requiring minimal
additional tooth preparation for indirectly fabricated restorations (onlays/overlays
or crowns). This is illustrated in Fig. 11.6a–c.
Fig. 11.6 (a–c) Interim

PMMA provisional crowns
(splinted on posterior teeth)
and directly built composite
resin onlays on anterior teeth
in preparation for laboratory-
fabricated composite resin
crowns to provide protection
and functional form during
orthodontic management.
Note missing 13 and 23
failure of eruption
Partial Veneers/Occlusal Overlays and Crowns
Veneers, overlays, or crowns restore missing tooth tissue by surrounding part or all
of the remaining natural structure [32]. They restore form, function, esthetics, and
longevity and provide protection. They are indicated for teeth with large occlusal
a b
Fig. 11.7 (a, b) Pre- and post-placement of a preformed gold onlay, cemented on unprepared
upper first molar using Panavia Ex
defects and are well described in restorative dentistry textbooks. Limitations

include patients who are unable to cooperate for the procedure, financial con-
straints, compromised pulpal or periodontal prognosis, or lack of adequate sup-
porting dentine. Veneers, overlays, or crowns may be preformed, laboratory
fabricated or generated by CAD–CAM technology in either the clinic or labora-
tory. Many materials are available or in development and include non-precious
alloys, acrylic, composite resin, ceramic, porcelain fused to metal, and gold
(Fig. 11.7a, b).
Outcomes
The outcomes are dependent on the exactness of the procedures and the quality and
quantity of underlying dentine [33]. These restorations require ongoing mainte-
nance and monitoring and eventual replacement during adulthood. The primary
goal in late childhood and adolescence should be to restore the teeth as effectively
as possible to preserve tissue for subsequent restorations.
Conclusion
It can be very difficult for practitioners to decide how best to restore newly
erupted permanent teeth that have hypomineralized or hypoplastic enamel. The
primary aim is to protect the teeth from further breakdown and caries and to
minimize sensitivity. In the anterior region, it is also important to address esthetic
concerns. The second aim is to protect the pulp to allow normal maturation so
that teeth will be permanently restorable in early adulthood. These goals are
achievable using a combination of adhesive resin materials and preformed
crowns including stainless steel crowns. These restorations can provide protec-
tion for up to 10 years during which time the developing occlusion can be man-
aged in a multidisciplinary manner involving dentists, pediatric dentists,
orthodontists, and prosthodontists. However, all this care is not without consider-
able cooperation from the child/young person. Practitioners should focus on pro-
viding the best interim solutions in the most acceptable way to the child and their
family which may include accessing sedation and/or general anesthesia in addi-
tion to local anesthetic.
References
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genesis imperfecta in children and adolescents. Cochrane Database Syst Rev. 2013;6:Cd007157.
2. Malik K, Gadhia K, Arkutu N, McDonald S, Blair F. The interdisciplinary management of
patients with amelogenesis imperfecta – restorative dentistry. Br Dent
J. 2012;212(11):537–42.
3. Munoz MA, Arana-Gordillo LA, Gomes GM, Gomes OM, Bombarda NH, Reis A, et al.
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Future Possibilities for Managing Dental
Enamel Defects: Recent and Current 12
Research Approaches
Agata Czajka-Jakubowska, Jun Liu, Sywe-Ren Chang,

and Brian H. Clarkson
Abstract
The cause of an enamel defect can be genetic, systemic, local, and/or induced.
The repair of these defects spans the fields from gene therapy to invasive or non-
invasive conventional restorative therapies. No matter how disfiguring some of
the genetic and systemic conditions are, it is unlikely that the modern techniques
of genetic and tissue engineering will be used in the near future to repair or pre-
vent these enamel defects. Clinicians will have to rely on more conventional
invasive, minimally invasive, and noninvasive techniques to treat this problem.
This chapter describes some new and novel techniques which are in use and/or
development for the repair of enamel defects. They include: growing enamel
crystals on dental substrates, penetration of carious lesions with self-assembling
molecules which encourage mineral formation, infiltrating carious lesions with
resins, a paint on “enamel” using a self-etch resin, and an “enamel” crystal con-
taining flexible laminate – a tooth “Band-Aid.”
Disclaimer The technology for the products described in the latter part of the chapter has been
licensed from the University of Michigan to a spin-off company, TruEnmel, of which the authors
are part owners.
A. Czajka-Jakubowska, PhD
Department of Maxillofacial Orthopedics and Orthodontics,
Poznan University of Medical Sciences, Poznan, Poland
J. Liu, PhD • S.-R. Chang, MS • B.H. Clarkson, BChD, MS, PhD (*)
Department of Cariology, Restorative Sciences and Endodontics,
School of Dentistry, University of Michigan, Ann Arbor, MI 48103, USA
e-mail: [email protected]; [email protected];
[email protected]

158 A. Czajka-Jakubowska et al.
Introduction
There are a wide range of putative causes of development defects of enamel (DDE)
including: genetic, for example, amelogenesis imperfecta (AI); systemic, which
causes a generalized disturbance of enamel formation, as in fluorosis; or local dis-
turbances causing hypoplasia. The etiology of DDE has been discussed in great
detail in Chaps. 1, 2, 3, 4, and 5. There are also acquired enamel defects, or those
which can be loosely defined as defects resulting from a disease, such as caries or
caused iatrogenically during the repair of a disease. Other acquired defects may
include cracks, abfractions, wear, and erosion. The potential to repair these defects
ranges from very complex gene therapy to the more conventional, invasive restor-
ative techniques. In the near future, it is expected that several forms of noninvasive
restorative therapy will become routine.
Genetic Engineering
Using genetic engineering to “cure” a genetic disturbance of enamel no matter how

disfiguring is unlikely in the short term until this technology is perfected on lethal
diseases and declared safe. Reports of bioengineered tooth development, including
successfully using differentiated stem cells to produce dental enamel and “teeth,”
suggest that in time, this technology may be mastered for clinical use [1]. However,
the issue of whether such “engineered” teeth can achieve useful function is another
area of research that will require significant effort. Function would include normal
enamel appearance especially in the anterior region, masticatory function, compat-
ibility with other tissues, and neurological responsiveness via the dentin to allow the
teeth to respond to stimuli in the oral cavity. One line of research has been focusing
on identifying specific cellular pathways that are affected by genetic mutations
resulting in altered amelogenesis (or enamel formation) leading to the eruption of
teeth with hypomineralized or hypoplastic enamel. Many such mutations have now
been identified, and our understanding of how each mutation affects the cellular
pathways is evolving. In at least one case, a mutation in the gene encoding the prin-
ciple developing enamel matrix protein, amelogenin, appears to result in protein
misfolding or premature aggregation such that it cannot be processed through the
normal cellular secretory pathways resulting in what is described as a “cell stress”
response. This can eventually cause apoptosis (cell death) [2]. Recent research of a
particular mutation in mice that results in defective enamel similar to that occurring
in human AI suggests that there may be opportunities to “rescue” the pathway in
several different ways. Brookes and co-workers [3] have shown rescue of the enamel
phenotype in female mice with an amelogenin mutation by a drug (sodium phenyl-
butyrate) that supports the cells to avoid apoptosis and thus go on to complete
enamel formation. This is a promising approach that has already been shown to
improve outcomes in other human diseases caused by particular mutations that
invoke cell stress. This line of enquiry in enamel development still requires many
years of research to translate into clinical use in humans. However, it has the poten-
tial to successfully improve enamel formation in permanent teeth if the problem can
12 Future Possibilities for Managing Dental Enamel Defects 159
be identified at birth or in the first few months of life. This would be possible given
a known family history. However, for many children AI is not diagnosed until the
permanent teeth start to erupt, and so this particular approach might only benefit
some of the later developing teeth.
One of the problems of using another recent medical technology, tissue engineer-
ing to develop new enamel, is that this is only applicable to tissues with living cells.
Unfortunately, the ameloblast undergoes apoptosis and dies once enamel has
reached maturity. This makes enamel regeneration impossible unless a source of a
person’s stem cells could be engineered or redirected to produce viable ameloblasts.
While this has been shown to be possible in in vitro conditions, how this enamel
could be used to “restore” enamel in erupted teeth remains a challenge. Therefore,
it is believed that the more conventional ways of treating defective enamel will con-
tinue for the foreseeable future.
Enamel Crystal Development
Growing biomimetic enamel crystals, both in vitro and in vivo, has been shown to be
possible by a number of scientific groups [4–10]. Studies have reported using enamel
proteins (amelogenin) [5, 6, 8], peptides and artificial proteins [11], and dendrimers
[4, 10] to promote the growth of fluorhydroxyapatite (FHA) on etched enamel sur-
faces. Other studies have used pure chemical solutions in an attempt to grow enamel-
like structures on etched enamel surfaces. Perhaps the most convincing of these is
that reported by Yin et al. in 2009 [12]. They were able, after 8 days and near physi-
ological conditions, to grow enamel-like crystals on etched human enamel surfaces.
The FHA crystal had the characteristic shape of human enamel crystals and a cal-
cium/phosphorus ratio of 1.59 similar to the expected ratio of FHA of 1.67. However,
whether the crystal growth would have occurred in the presence of saliva which
contains crystal growth inhibitors including statherin is debatable. The artificial pro-
tein, polyamidoamine dendrimers (PAMAM) have been used as scaffolds for enamel-
like crystal growth in both in vitro and in vivo studies [4, 10]. The PAMAM
dendrimers are modified with carboxylic acid groups (COOH) that allows them to be
adsorbed onto etched enamel surfaces where they act as a template for enamel-like
crystal formation. Further modification with alendronate (ALN) increases the bind-
ing strength to the etched enamel. These modified dendrimers were used in an in vivo
study where they were adsorbed onto enamel sections and sewn to the inside of rat
cheeks [10]. After 28 days, the sections were removed, and enamel coatings ana-
lyzed. The coatings had a calcium/phosphorous ratio of 1.67 identical to the ratio of
human enamel apatite, but the images of the crystals did not show the normal mor-
phology of human enamel crystals. Enamel-like crystals have been successfully
grown on various substrates, dentin, the amelodentinal junction, and metal (implant)
surfaces [13]. Thus, this technology is available, but problems do exist when attempt-
ing to translate it for in vivo use. The crystals grow slowly; there is low strength of
adhesion of the crystals to the substrate; and the crystals have to be protected during
their growth phase from the forces of mastication, tooth brushing, hot and cold
drinks, and occasionally the low pH of these drinks.
Another approach has been to infiltrate demineralized lesions with self-

assembling peptides [11]. These peptides then self-assemble to produce a molecule
that attracts calcium, resulting in laying down mineral within the subsurface lesion.
Recently, a clinical trial demonstrated the remineralization potential of these pep-
tides [14]. Translating this approach to improving hypomineralized enamel presents
different problems that are related to the increased and different types of protein in
the lesions, but future research is expected to overcome the problems of the protein
and allow improvement of mineral-deficient enamel.
A somewhat different approach that combines repair and caries prevention has
been investigated. It focuses on the concept of noninvasive dentistry. The concept is
based on the knowledge that caries is caused by bacteria which die or at least
become quiescent once deprived of nourishment. Thus, there is no need to remove
diseased demineralized or hypomineralized enamel or carious dentin, as long as the
bacteria are deprived of any nutrients. This effect of sealing bacteria in tissue has
been reported in several studies over the past 30 years or more, the classic being the
study of Mertz-Fairhurst et al. [15]. This study clearly showed that carious dentin
left in teeth which had been completely sealed, thus depriving the bacteria of nour-
ishment, did not show caries progression after 10 years. The success of sealing
teeth, the difficulty in deciding when to re-restore, and an understanding of the dam-
age to teeth caused by re-restoration of teeth should be strong influences in support-
ing the concept of noninvasive restorative dentistry [16]. It should awaken dentistry
from its scientific slumber and base the management of diseased dental tissues on
current and new scientific and clinical evidence and not just remain reliant on the
teaching and practices of the past.
Two recent technologies “filling without drilling,” which purport to be noninva-
sive, do in fact have a degree of invasiveness because they require the removal of the
surface layer of non-cavitated demineralized enamel lesions by acid etching to
allow penetration of the lesion by the material being used. One of these, DMG Icon
low viscosity resin, is already in clinical use, and the outcomes of a clinical trial of
the other, using self-assembling peptides, have recently been reported. The Icon
technology marketed by DMG involves etching the enamel surface with hydrochlo-
ric acid which allows infiltration of the subsurface lesion with a low viscosity resin
which is then cured thus sealing the defect [17, 18]. However, this technique of
infiltration has not yet been demonstrated to be as successful in hypomineralized
lesions [19]. The other technology using self-assembling peptide molecules to infil-
trate the lesion and promote remineralization has been described above [11, 14, 20].
Both of these technologies are an improvement on the “drill and fill” approach
which is still very common in dentistry today, and it is hoped that similar technolo-
gies will be able to be utilized for hypomineralized lesions in the future.
Researchers have considered that the approach using low viscosity resin like the
Icon technique could be improved by the introduction of enamel-like nanocrystals
into the resin prior to the application of the resin, therefore producing an enamel-
like crystal-filled subsurface lesion. Another biochemical application, in contrast to
the self-assembling peptides, is to use a phosphoprotein or a phosphorylated peptide
like serine. This protein or peptide having infiltrated the carious lesion, either in
Fig. 12.1 FHA crystals

synthesized under hydrother-
mal conditions
Fig. 12.2 FHA crystals

synthesized under ambient
conditions
enamel or dentin, would “catalyze” the formation of mineral from plaque fluid and/
or saliva [21].
In 2006, a landmark paper by Chen et al. described the in vitro synthesis of FHA
crystals and their ability to coat a substrate with these crystals which had a prism-
like structure resembling the surface of human enamel [22]. The effects of these
coatings on the in vitro and in vivo response of various cell lines have been reported
[23–25]. In 2013, Clark et al. reported the anticariogenic effect of FHA coated pre-
formed stainless steel crowns at the tooth/crown margin in an in vitro model [26].
These enamel-like crystals and coatings are synthesized without the use of cells or
proteins. They can be produced under hydrothermal (Fig. 12.1) or ambient condi-
tions (Fig. 12.2). The crystals resemble enamel crystals in shape, composition, and
size. The larger FHA crystals seen in Fig. 12.1 are produced by applying heat and a
Fig. 12.3 “Paint on enamel”

for the treatment of enamel
defects including early
carious lesions. It can also be
tinted to match the tooth
color or in this case to whiten
discolored teeth. Right half of
the tooth was painted with
self-etch adhesive plus FHA
crystals and titanium dioxide
Fig. 12.4 SEM observation

of the “paint on enamel”
layer on the enamel surface
showing the intimacy of
contact between the “paint on
enamel” and the tooth
small amount of pressure for 10 h. The crystals synthesized under ambient condi-
tions are smaller and take up to 1–3 days to form. All the crystals are produced from
a solution containing calcium, phosphorus, and fluoride. Irrespective of how they
are synthesized, the crystals have a calcium/phosphorus ratio of approximately
1.67, the same as human enamel crystals, and an x-ray diffraction pattern typical of
FHA [27].
The crystals have been incorporated into several different vehicles including res-
ins, a laboratory-synthesized substance that resembles the “glue” that allows mol-
lusks to adhere to rocks in the ocean and water. Variations of these mixtures could
be used in the treatment and prevention of caries, tooth sensitivity, and erosion or to
“whiten” discolored teeth. An ideal vehicle for the FHA crystals might be any of the
self-etch adhesives which are now used routinely in dentistry. The concept is that
this combination can be used as a “paint on” enamel. Because of the acid nature of
the adhesive, it will bond to enamel and dentin allowing it to cover those surfaces
with a layer of enamel crystals. It can be tinted to match the color of the tooth or to
whiten a discolored tooth (Fig. 12.3). It could also be used to repair carious and
erosive lesions (Fig. 12.4), as an occlusal sealant (Fig. 12.5) or as desensitizing
Fig. 12.5 “Paint on enamel”

to seal molar occlusal
surfaces. (a) Whole occlusal
surface sealed. (b) Fissures
only sealed. (c) Right half
occlusal surface sealed
a c
b
Fig. 12.6 SEM image of

“paint on enamel” occluding
a dentinal tubule
Fig. 12.7 Fluoride release

from a bis-GMA/TEGDMA
composite of different filler
% vol. of unsilanated and
silanated FHA crystals for
1 day, 1 week, and 1 month
agent (Fig. 12.6) – a five-in-one product. One further advantage of this technology
is that it will release fluoride over time even if incorporated into a resin (Fig. 12.7).
This will allow not only the treatment options described above but may also have a
caries-preventive effect by promoting remineralization or possibly continuing
Fig. 12.8 Flexural strength

and elastic modulus (%) of a
bis-GMA/TEGDMA
composite filled with
silanated silica (Ssilica)
particles and nonsilanated FA
(NSFHA) crystals
Fig. 12.9 (a) Brittle

FHA films and (b) pliable
FHA/Euradgit films
mineralization in teeth which are hypomineralized at eruption such as those with

hypomineralized AI or MIH a though this has yet to be established. Large structural
defects could be restored with a composite material that is partially filled with the
FHA crystals (Fig. 12.8). As can be seen in Fig. 12.8, the mechanical properties of
the composite material are not diminished if FHA crystals are substituted for 20 %
of the silanated silica. This “paint on” enamel technology again promotes the con-
cept of noninvasive dentistry where it can be applied over early demineralized
lesions on smooth or occlusal surfaces. Further research is now required to evaluate
this technology in in vivo settings and clinical trials.
It has also been shown that the FHA crystals can be produced as a film
(Fig. 12.9), but these tend to be brittle and unsuitable for use as laminates. It is
thought that laminates could have a temporary role in protecting lesions, including
hypomineralized lesions, while they are mineralizing. In order to obtain a flexible
Fig. 12.10 (a) Human

a
incisor tooth and FHA/
Euradgit laminate and
(b) FHA/Euradgit laminate
applied to the buccal surface
of human incisor tooth
laminate which would conform to the curved surface of a tooth, the crystals have
been mixed with a polymer with the trade name of Eudragit. This is used as an
enteric coating for tablets (e.g., aspirin) and it dissolves at various pHs. It has the
advantage of being approved by the Federal Drug Administration in the USA for
use in humans. This laminate is white in appearance and is flexible (Fig. 12.10a).
It can be cut to any size and is easily adapted to the curved surface of a tooth. It can
be bonded to the tooth surface, or, if allowed to dry on the tooth, it will adhere to
that surface. It could be used like a “Band-Aid” to cover discolored, defective
enamel and early carious lesions without removing any tooth tissue. The laminate
is esthetic and will cover large areas of tooth surface (Fig. 12.10b). It is hoped that
as the Eudragit dissolves over time, the FHA crystals will become incorporated
into the enamel surface producing a surface with high-fluoride content. This lami-
nate will achieve an esthetic repair along with caries-preventive activity – a nonin-
vasive approach.
The latter part of this chapter has described two potential products for the repair
and prevention of enamel defects. Prototypes of these modalities have already been
tested in vitro and are good examples of potential noninvasive type of products.
There is now the need for them to undergo clinical testing to establish their useful-
ness in clinical practice.
Conclusion
It can be seen from current research approaches that the future will hold many
new approaches to managing teeth not only with enamel defects but also with
defects created by dental caries and dental trauma of various kinds. The
approaches will be influenced by improved understanding of genetic effects at
the cellular level and by how these might be modified. They will also be influ-
enced by the development of biomimetic materials for use throughout the body.
This will require dental practitioners to engage with the new technologies and to
embrace the evolving understanding of dental hard tissues in health and disease.
To do this, the profession needs to continue to move from a primarily restorative
approach to treating diseases of the dental hard tissues that involves removal of
damaged tissue to one which alters and modifies the tissues even when
defective.
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Final Comments
13
Bernadette K. Drummond and Nicky Kilpatrick
Abstract
This chapter sums up the information provided by an international group of
authors on dental enamel defects (DDE) in children and adolescents. It com-
ments on the difficulty of identifying defects in individuals based on indices that
have been developed for prevalence studies. It comments on the significant
impact DDE have on quality of life and notes the difficulties in providing care
that exists because of limited evidence of outcomes from different procedures.
Finally it encourages clinicians to work with dental specialists in early childhood
to plan the best available path to the permanent dentition.
Developmental defects of enamel (DDE) account for an apparent increasingly large

burden of dental treatment required in children and adolescents. Despite a plethora
of studies and overwhelming anecdotal clinical reports, there remain difficulties and
wide variation in describing and defining these defects. There are limitations in all
of the reported indices which, while useful in epidemiological studies, are often not
appropriate in the clinical setting when trying to understand or diagnose DDE in an
individual case. Currently, even when a label is assigned to a particular type of
defect, it often does not indicate the treatment approach that should be followed.
This is best illustrated by Molar Incisor Hypomineralization (MIH) which, has been
recognized for many years but only recently identified as a unique DDE condition
and as such, still has no defined management path. There have been many reports


170 B.K. Drummond and N. Kilpatrick
describing the structure and composition of the compromised enamel in the differ-
ent presentations of DDE. More recently, reports describing the genetic influences,
including specific mutations, linked to different types of DDE have been appearing
in the literature. However, management remains a very real challenge for clinicians
and patients alike. While there are many case reports of clinical management of
DDE, there is still no good evidence for proven successful ways to manage DDE in
very young children or through adolescence until permanent restorative solutions
can be provided.
With these considerations in mind, this book has been written by a group of
authors, colleagues, and friends, all of whom have wide experience investigating
and managing DDE. The aims are to summarize what is currently known about the
prevalence and etiology of DDE and to provide guidance for clinicians when faced
with managing DDE in children and adolescents. We hope to encourage interest in
providing care for these children and adolescents to allow them to reach adulthood
as confident young people with healthy smiles and functioning dentitions. The
growing awareness of the broader impacts of DDE on young people, and in particu-
lar their oral health-related quality of life, has been recognized and is reviewed.
Where the defects involve anterior teeth, appearance is compromised which has a
significant impact on the affected individual particularly when other children or
adults comment on their “different” teeth. Furthermore, defective enamel is often
sensitive with young children complaining they cannot eat ice cream. It follows that
oral hygiene and tooth brushing in particular is likely compromised and prevention
of dental caries may be more difficult. Options for decreasing sensitivity to help
with preventive care are discussed.
Unlike caries, there is still no good evidence to support reliable approaches to the
management of different types of DDE during childhood. This book presents a
range of options for maintaining the primary and young permanent dentitions
throughout childhood. These options include optimizing appearance, in terms of
both the color and shape of teeth as well as the occlusion; reducing sensitivity;
maintaining function; minimizing wear and caries as well as promoting healthy
periodontal tissues; and most importantly of all helping these young people to
develop dental coping skills for the long-term complex restorative care that may be
required well in to adulthood.
This book has drawn on the experience, skills, and research outcomes from den-
tal clinicians and researchers across the world. It has allowed these writers to sum-
marize their knowledge and to challenge others to think about and realize their role
in recognizing DDE, recording what they see, and ensuring, where appropriate, that
these dental problems are recorded alongside any other general health problems. In
this way dental professionals can contribute to advancing understanding of the links
between genetic/medical conditions and DDE which will, in turn, inform develop-
ment of technological approaches to rescuing teeth before the defects develop.
We hope that readers will be able to use the information in this book in their man-
agement of DDE and that they will continue to seek better restorative solutions for
these problems and collaborate with specialists including pediatric dentists, ortho-
dontists, prosthodontists and researchers in tooth development to allow patients and
parents to have a long-term vision of healthy and functional smiles in adulthood.
Index
A Celiac disease, 8
Adverse perinatal conditions, 6–7 Cementoenamel junction (CEJ), 78
Ameloblasts Child Oral Health Impact Profile
direct genetic effect, 54–56 (Child OHIP), 86
indirect effect, 50–53 Child Oral Impacts on Daily Performances
nongenetic effect, 46–49 (Child OIDP) Questionnaire, 86
Amelodentinal junction (ADJ), 75, 76 Child Perceptions Questionnaires
Amelogenesis imperfecta (AI), 6, 25, 55 (CPQ11–14 and CPQ8–10), 86
classification of, 60–61 Chronological hypoplasia/hypomineralization,
future directions and, 69–70 124, 125
genes and function, 63, 64 CNNM4, 55
hypocalcified (see Hypocalcified AI) Composite resin, direct restoration with
hypomaturation (see Hypomaturation AI) contraindications, 144
hypoplastic (see Hypoplastic, AI) indications, 144
malocclusion and, 69 outcomes, 145–146
Mendelian inheritance, 61–63 technique, 145
nomenclature and genetic basis for, 62, 63 venners (see Direct composite veneers)
psychosocial impacts of, 88–89 Computerized tomography (CT), 80
with taurodontism, 69 C4ORF26, 66
AMELX, 63, 66 Cystic fibrosis (CF), 51, 52
Autosomal recessive cone-rod dystrophy, 55 Cystic fibrosis transmembrane regulator
protein (CFTR), 51, 52
B
Birth trauma, 6–7 D
Bleaching DDE. See Developmental defects of enamel
contraindications, 143 (DDE)
indications, 143 Deciduous molar hypomineralization
outcomes, 144 (DMH). See Hypomineralized
techniques, 143–144 second primary molars (HSPM)
Dental anxiety, 91
Dental fluorosis, 87–88
C Developmental defects of enamel (DDE)
Casein phosphopeptide-amorphous calcium in adolescents, 169–170
phosphate (CPP-ACFP/ACP), bonding protocols, 99
118–119 child-centered approaches, 86–87

and Contemporary Management, DOI 10.1007/978-3-662-44800-7
172 Index
Developmental defects of enamel (DDE) (cont.) extraction, 135–136

in children, 169–170 hereditary conditions (see Hereditary
classification, 46 conditions, DDE)
clinical interim restorations, 130
examination, 102–103 longer-term restorations, 130–135
history, 101 management, 126
implications, 95 pain and anxiety management,
crystal development 128–129
dendrimers, 159 presentations of, 2–3
FHA (see Fluorhydroxyapatite (FHA) prevalence, 3–4
crystal) prevention, 126–127
filling without drilling approach, 160 quantitative deficiencies of, 2
Icon technique, 160 reducing sensitivity, 127–128
noninvasive dentistry, 160 restorative management, 129–130
PAMAM, 159 systemic factors, 124
self-assembling peptides, 160 trauma causing, 11
dental caries and erosion psychosocial impacts of
eruption, 115 AI (see Amelogenesis imperfecta (AI))
preventive agents, 116–118 dental fluorosis, 87–88
preventive strategy, 115–116 qualitative and quantitative approaches,
qualitative defects, 114–115 87
surface integrity and bacterial teasing and bullying, 90–91
adhesion, 114 unknown Etiology, 89–90
descriptions, 100 radiographic examination, 103
extraction social judgments
outcomes, 107–110 appearance-related, 94
planning, 106–107 children’s views of other children with,
financial implications, 100 94–95
gene mutation, 158 surface sealing
genetic engineering, 158–159 methods, 119–120
genetic systemic disease (see Genetic resin infiltration, 119
systemic disease) sealants, 118–119
growth and development assessment, systemic disease (see Systemic disease)
104–105 treatment
histological examination, 104 dental anxiety, 91
hypersensitivity, 113–114 intervention timing, 92–93
media and celebrity industry, 86 outcome measures, 91–92
medical examination, 104 treatment planning, 105–106
permanent dentition, 15–16 Dietary counseling, 116
environmental factors, 23–25 Direct composite veneers
etiology, 16–20 contraindications, 147
generalized enamel defects, 21–23 indications, 147
genetic disorders, 25 outcome, 147–148
localized enamel defects, 21 for upper incisors, 146
prevalence, 16–18 uses, 146
systemic conditions, 25–26 DLX3, 69
permanent teeth
periodontal management of
(see Permanent dentition) E
restorative management of Early childhood caries (ECC), 1–2
(see Permanent dentition) ENAM, 64
primary dentition Enamel formation, 1, 2
distribution, 4–5 Enamel hypomineralization, 23, 24
etiology, 5–6, 124–126 Enamel hypoplasia, 2
Index 173
central and lateral incisors affected birth trauma and adverse perinatal
by, 5, 7 conditions, 6–7
DDE quantitative deficiencies, 2 celiac disease and gastrointestinal
prevalence of, 1 malabsorption, 8
tetracyclines, 10 chemicals and toxins, 9–10
tooth with, 4 generalized inherited disorder/syndrome, 6
Enamel mineralization, 2–3 infections, 8–9
Enamel morphogenesis, 16 isolated cleft lip and palate, 8
Enamel-renal syndrome/Enamel-renal-gingival liver and renal conditions, 8
syndrome, 55 malnutrition and nutritional deficiencies, 8
Endotracheal intubation, 7 premature birth, 7
Environmental factors, 23–25 Hyperbilirubinemia, 7, 9
Epidermolysis bullosa (EB), 55, 56 Hypocalcified AI, 68
European Academy of Pediatric Dentistry Hypomaturation AI
(EAPD), 33 AMELX, 66
enamel mineralization degree, 67
KLK4, 66
F MMP20, 66
FAM20A, 63–65 phenotypes, 65
FAM83H, 68 preoperative photograph of child with, 134
Fluorhydroxyapatite (FHA) crystal types, 67
advantage, 163–164 Hypomineralization
ambient conditions, 161–162 composition, 81–82
brittle films, 164 enamel, 23, 24
flexural strength and elastic modulus, 164 fluorotic, 23
human incisor tooth, 165 hardness and elasticity modulus, 77
hydrothermal conditions, 161 macroscopic changes, 75–76
paint on enamel maxillary/mandibular incisor
early carious lesions, 162 teeth, 18–19
occlusal sealant, 162, 163 mechanical properties, 76–77
SEM observation, 162, 163 microstructure, 77–81
vehicle for, 162 TEM image of, 79
Fluorosis, 23–24 Hypomineralized and/or hypoplastic teeth.
See Developmental defects
of enamel (DDE)
G Hypomineralized second primary molars
Gastrointestinal malabsorption, 8 (HSPM)
Generalized enamel defects, 21–23 clinical implications, 39–40
Genetic disorders, 19, 25 diagnosis, 33
Genetic systemic disease etiology, 38
CF (see Cystic fibrosis (CF)) goals, 40
OMIM, 53 mild, 32, 33
rickets, 50 prevalence, 38–39
TS (see Tuberous sclerosis (TS)) Hypomineralized teeth, clinical management
VDDR, 50, 51 tree, 120
XLHR, 50–52 Hypoparathyroidism, and enamel defects, 6
Glass ionomer cement (GIC), 118 Hypoplasia, 34
intra-radicular infection, 19
maxillary central incisors, 18, 20
H secretory stage of amelogenesis, 20
Hall technique, 134 Hypoplastic
Hereditary conditions, DDE AI
acquired systemic conditions, 6 AMELX, 63
amelogenesis imperfecta, 6 ENAM, 64
174 Index
Hypoplastic (cont.) diagnosis, 33

FAM20A, 63–65 etiology, 36–38
LAMB3, 64–65 factors putatively associated with, 36, 37
preoperative photograph of child gingival margin, 102
with, 134 goals, 40
preoperative image, 124, 125 hypomineralized enamel
(see Hypomineralization)
inorganic component, 81
I mineral density, 80
Indirect interim restorations, 151–152 permanent incisors, 32
Infections, during pregnancy, 8–9 prevalence, 38, 39
Inherited dermatological syndromes, 6 rapid caries and post-eruptive
Isolated cleft lip and palate, 8 breakdown, 74
serum proteins, 82
shiny surface appearance, 34
J sound enamel, 74–75
Jalili syndrome. See Amelogenesis Mouth prevalence, permanent dentition, 16
imperfecta (AI)
N
K Neonatal line, 3
Kallikrein 4 (KLK4), 82 Nutritional deficiencies, 8
Kinder Krowns®, 135
O
L Occlusal overlays and crowns, 152–153
LAMB3, 64–65 Online Mendelian Inheritance in Man
Laryngoscopy, 7 (OMIM), 53
Liver, in DDE, 8 Oral health-related quality of life (OHRQoL)
Localized enamel defects, 21 questionnaires, 86
Longer-term restorations Oral hygiene, 116
anterior teeth, 133, 135, 136
molar teeth
composite resin, 130–132 P
preformed crowns, 132–135 Panoramic radiography, 103
Low birth weights of adolescent, 109
DDE in primary teeth, 25 outcome of extracting, 107–108
systemic disease, 46–47 9-year-old female, 109, 110
Partial veneers, 152–153
Permanent dentition
M calcification and eruption dates, 16
Malnutrition deficiencies, 8 dose-response relationship, 24
Malocclusion, 110 enamel defects formation, 15–16, 22
Microabrasion environmental factors, 23–25
contraindications, 142 etiology, 16–20
indications, 141 generalized enamel defects, 21–23
outcome, 142, 143 genetic disorders, 25
technique, 142 localized enamel defects, 21
Molar incisor hypomineralization luxation injuries, 21
(MIH), 169–170 mouth and tooth prevalence, 16
children with, 74, 91 periodontal management of
clinical features, 34–36 gingival recontouring and crown
with clinical obvious opacities, 76 lengthening, 150–151
definition, 36 indirect interim restorations, 151–152
Index 175
partial veneers/occlusal overlays S

and crowns, 152–153 Scanning electron microscopy (SEM),
prevalence, 16–18 75, 77, 79–80
restorative management of Sealants, 118–119
anterior teeth, 141 Sound enamel
bleaching agent, 142–144 enamel mineral, 74
composite resin, 144–148 hardness and elasticity modulus, 77
materials and techniques, 140–141 inter-rod areas, 75
microabrasion, 141–142 mechanical properties, 77
planning and trialing, 148–149 microstructure, 79
porcelain veneers, 148 organic component, 75
SSC (see Stainless steel crowns (SSC)) Stainless steel crowns (SSC)
systemic conditions, 25–26 contraindications, 149
Polyamidoamine dendrimers (PAMAM), 159 indications, 149
Posteruptive breakdown (PEB) outcomes, 150
anterior teeth, 115 radiographic appearance, 150
defects of enamel quality, 113 technique, 149
loss of enamel, 34 Systemic disease
surfaces, 117 celiac disease, 47–49
Premature birth, 7, 46–47 childhood oncology, 49
Prenatal factors, 6 Nephrotic syndrome, 47
Primary dentition preterm and low birth weight infants,
distribution, 4–5 46–47
enamel defects in, 1–2, 11 renal disease, 47
enamel formation, 1
etiology, 5–6, 124–126
extraction, 135–136 T
hereditary conditions (see Hereditary Taurodontism, 69
conditions, DDE) Thylstrup-Fejerskov Index (TFI), 87–88
hypoparathyroidism, 6 Tooth prevalence, in permanent dentition, 16
infections during pregnancy, 8–9 Toxins, 9–10
interim restorations, 130 Transmission electron microscopy (TEM), 79
longer-term restorations, 130–135 Tricho-dento-osseous syndrome (TDO), 54
anterior teeth, 133, 135, 136 Tuberous sclerosis (TS), 52, 53
molar teeth, 130–135
management, 126
mild diffuse opacities in, 9–10 V
pain and anxiety management, 128–129 VDDR. See Vitamin D-dependent rickets
and postnatal factors, 8 (VDDR)
presentations of, 2–3 Viral infections, during pregnancy, 9
prevalence, 3–4 Vitamin D deficiency, during pregnancy, 6
prevention, 126–127 Vitamin D-dependent rickets (VDDR),
quantitative deficiencies of, 2 25, 50, 51
reducing sensitivity, 127–128
restorative management, 129–130
systemic factors, 124 W
tooth crown formation of, 3 WDR72, 66
trauma causing, 11
R
RAS/MAPK pathways syndrome, 54–56
Renal diseases, 8

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Planning and Care

for Children and

Planning and Care for

ISBN 978-3-662-44799-4 ISBN 978-3-662-44800-7 (eBook)

Library of Congress Control Number: 2014955065

© Springer-Verlag Berlin Heidelberg 2015

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

The prevalence of developmental defects of enamel (DDE) is reportedly increasing

appropriate to extract these compromised teeth. However, it is important to consider

Dunedin, New Zealand Bernadette Kathleen Drummond, BDS, MS, PhD

Professor J. Kirkham for her insights into Chap. 13.

1 Dental Enamel Defects in the Primary Dentition:

10 Restorative Management of Dental Enamel Defects

Robert P. Anthonappa, BDS, MDS, PhD Department of Paediatric Dentistry,

Winifred Harding, BDS, MDS Department of Oral Sciences,

W.K. Seow, BDS, MDSc, PhD, DDSc

© Springer-Verlag Berlin Heidelberg 2015 1

Presentations of Developmental Defects of Enamel (DDE)

Table 1.1 Chronology of tooth crown formation of the primary dentition

Table 1.2 Prevalence of DDE in the primary dentition by country

in prevalence rates among different countries and population groups. A Chinese

Table 1.3 Etiology of Generalized defects

Generalized Inherited Disorder or Syndrome with DDE

Acquired Systemic Conditions

Birth Trauma and Adverse Perinatal Conditions

Fig. 1.1 The maxillary

bilirubin (hyperbilirubinemia) associated with systemic conditions such congenital

Isolated Cleft Lip and Palate

Malnutrition and Nutritional Deficiencies

Liver and Renal Conditions

Celiac Disease and Gastrointestinal Malabsorption

Fig. 1.2 (a) The restored

Chemicals and Toxins

Fig. 1.3 A mandibular

Other Systemic Conditions

Local Factors Causing DDE

© Springer-Verlag Berlin Heidelberg 2015 15

Table 2.1 The calcification and eruption dates of permanent teeth

Permanent Calcification Crown formation Eruptiona

Prevalence of DDE in the Permanent Dentition

Etiology of DDE in the Permanent Dentition

F level Age Prevalence %

Table 2.2 (continued)

F level Age Prevalence %

Fig. 2.1 Hypoplasia of the

Fig. 2.2 Hypomineralization

in amelogenesis imperfecta (see Chap. 5) or as enamel defects associated with other

Fig. 2.4 (a) Hypoplasia of

Determining the Etiology

Localized Enamel Defects

Generalized Enamel Defects

Fig. 2.5 (a) Fluorosis is

may be related to fluoride, a careful history of total fluoride ingestion as well as

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders that

concentrations of Ca2+ and Pi prevent proper mineralization of the organic bone

The prevalence of DDE in the permanent dentition (in developed countries) is

Karin L. Weerheijm, Marlies E.C. Elfrink,

K.L. Weerheijm, PhD (*)