American Journal of Medical Genetics 29581-594 (1988)

International Nosology of Heritable

Disorders of Connective Tissue,
Berlin, 1986
P. Beighton, A. de Paepe, D. Danks, G. Finidori, T. Gedde-Dahl,
R. Goodman, J.G. Hall, D.W. Hollister, W. Horton, V.A. McKusick,
J.M. Opitz, F.M. Pope, R.E. Pyeritz, D.L. Rimoin, D. Silence,
J.W. Spranger, E. Thompson, P. Tsipouras, D. Viljoen,
1. Winship, and 1. Young
Cape Town, South Africa, (P.B., 5.V., 1. W.); Ghenf, Belgium (A. de P.);
Melbourne, Australia (D.D.); Paris, France (G.F.); Oslo, Norway (T. G-D.);
Tel-Hashomer, Israel (R. G.); Vancouver, Canada (J.G.H.); Portland,
Oregon. U.S.A. (0. W.H.); Houston, Texas, U.S.A. (W.H.); Baltimore,
Maryland, U.S.A. (V.A. McK., R.E.P.); Helena, Montana, U.S.A. (J.M.O.);
London, U.K. (F.M.P,, E. T.); Torrance, California, U.S.A. (0.
L.R.); Sydney,
Australia (5.S.); Mainz, West Germany (J. W.S.); Farmington, Connecticut,
U.S.A. (P. T.); Leicester, U.K. (I. Y.)

INTRODUCTION
The heritable disorders of connective tissue have proven to be very heterogeneous
and problems have arisen concerning syndromic boundaries, nomenclature, and classifica-
tion. In an attempt to resolve these dilemmas, a group of experts participated in a
Workshop held during the 7th International Congress of Human Genetics, Berlin, in
September, 1986. The program for this Workshop had been drawn up at a planning
meeting held in 1985 at the Ciba Foundation, London (Beighton, Hollister, Pope,
Pyeritz).
At the Workshop, overviews were given of the uses and limitations of nosology
(McKusick), diagnostic criteria (Pyeritz), and practical issues in biochemical and
molecular diagnosis (Hollister). Invited speakers then gave brief comments on the current

Received for publication June 24, 1987; revision received August 3, 1987.

Address reprint requests to Prof. Peter Beighton, MRC Unit for Inherited Skeletal Disorders, Department of
Human Genetics, University of Cape Town, Medical School, Observatory 7925,Cape Town, South Africa.

0 1988 Alan R. Liss, Inc.

582 Beighton et al.

status of the nosology of specific categories of inherited connective tissue disorders and
made recommendations for possible modification.
The Workshop was followed by two closed committee meetings at which the
participants attempted to reach agreement on syndromic definition and a standardized
nomenclature. The final proposals, with brief comment where relevant, form the subject of
this communication.

GENERAL COMMENTS
1. This “Berlin Nosology” is not intended to intrude upon or cut across the existing
Paris Nomenclature for constitutional disorders of the skeleton [Maroteaux et al., 19861.
Inevitably, there is some overlap, but wherever possible this has been avoided.
2. In some conditions current problems revolve around diagnostic criteria or
syndromic boundaries, while in others nomenclature and classification are the main issues.
For these reasons, the style of presentation in this article is not necessarily uniform.
3. Some heritable connective tissue disorders can be subclassified on a clinical basis
or through biomolecular abnormalities; in others the basic defect is still unknown. The
nosology represents a synthesis of these factors, based on current knowledge, and future
modification is foreseen. The Committee plans to meet at regular intervals for updating.
4. A number of conditions, including heteroglycanoses, overlap syndromes and tight
joint syndromes were also discussed at the Workshop and Committees. There was general
consensus that disorders in these categories were outside the scope of this document.
5. Key references are provided for each disorder. The catalogue of inherited
disorders “Mendelian Inheritance in Man” [McKusick, 19861 and the classical mono-
graph “Heritable Disorders of Connective Tissue” [McKusick, 19721 are additional rich
sources of references and information. Other relevant reviews have been published by
Byers [ 19831, Maroteaux et al. [ 19863, and Pope and Nicholls [ 19871.
6. Where relevant the numbers allocated to entities in “Mendelian Inheritance in
Man” [McKusick, 19861 have been cited in the titles of the disorders mentioned in this
nosology.
7. A need for a register of researchers, projects, and affected persons was recognized
and a subcommittee has been established under the chairmanship of Dr. Reed Pyeritz. A
report on conclusions and proposals is appended.

1. MARFAN SYNDROME ( 15470)

Diagnostic manifestations (Listed in approximate order of decreasing specificity. Major
manifestations indicated by an asterisk)
Skeletal
anterior chest deformity, especially asymmetric pectus excavatum/carinatum
dolichostenomelia not due to scoliosis
arachnodactyly
vertebral column deformity
scoliosis
thoracic lordosis or reduced thoracic kyphosis
tall stature, especially compared to unaffected 1O relatives
high, narrowly arched palate and dental crowding
protrusio acetabulae
 Berlin Nosology 583
abnormal appendicular joint mobility
congenital flexion contractures
hypermobility
Ocular
*ectopia lentis
flat cornea
elongated globe
retinal detachment
myopia
Cardiovascular
*dilatation of the ascending aorta
*aortic dissection
aortic regurgitation
mitral regurgitation due to mitral valve prolapse
calcification of the mitral annulus
mitral valve prolapse
abdominal aortic aneurysm
dysrhythmia
endocarditis
Pulmonary
spontaneous pneumothorax
apical bleb
Skin and integument
striae distensae
inguinal hernia
other hernia (umbilical, diaphragmatic, incisional)
Central nervous system
*dural ectasia
lumbosacral meningocele
dilated cisterna magna
learning disability (verbal-performance discrepancy)
hyperactivity with or without attention deficit disorder
Genetics
Autosomal dominant inheritance
25-30% of cases are sporadic; paternal age effect
Requirementsfor diagnosis
In the absence of an unequivocally affected lo relative:
Involvement of the skeleton and at least 2 other systems; at least one major
manifestation
In the presence of at least one unequivocally affected lo relative:
Involvement of at least 2 systems; at least one major manifestation
preferred, but this will depend somewhat on the family’s phenotype
Urine amino acid analysis in the absence of pyridoxine supplementation confirms
absence of homocystinuria
Conditions most often considered in diflerential diagnosis
homocystinuria
familial or isolated mitral valve prolapse syndrome
familial or isolated annuloaortic ectasia (Erdheim disease)
584 Beighton et al.
congenital contractural arachnodactyly
Stickler syndrome
Comments
The syndromic status of congenital contractural arachnodactyly is uncertain; most
patients so diagnosed likely have the Marfan syndrome.
The Marfanoid hypermobility syndrome is not a distinct entity.

2. STICKLER SYNDROME (10830)

Alternative designation: Hereditary arthrophthalmopathy .
Excludes: Marshall and Wagner syndromes, which are apparently
different entities.
Weissenbacher-Zweymiillersyndrome, which is a severe
early form of the Stickler syndrome in some familites. This
eponym should be discarded.
Manifestations
Stickler syndrome is a common pleiotropic autosomal dominant syndrome with the
following variable manifestations:
Myopia and retinal detachment, rarely congenital cataracts
Arthropathy, mild, with skeletal manifestations sometimes called mild spondyloepiphy-
seal dysplasia
Deafness
Physique, normal or “Marfanoid habitus,” with joint hypermobility
Short midface
Cleft palate
Cardiac defects, rare
The condition is an “iceberg trait” in many families; severely affected propositi may have
mildly affected relatives with minor stigmata. The condition should be suspected in all
cases of apparently isolated congenital cleft palate, of Pierre Robin anomaly, all
Kniest-like cases in infancy, and autosomal dominant myopia with retinal detachment.
Recent tight linkages between the Stickler syndrome and the COL2A1 locus in one large
pedigree suggests that the basic defect is in the primary structure of alpha l(I1)
procollagen. Genetic heterogeneity must be investigated before using DNA probes for
COL2A1 in diagnosis.
3. EHLERS-DANLOS SYNDROME (EDS)
Redundant synonym “cutis hyperelastica”
Excludes “cutis laxa” and “familial joint hypermobility syndrome”
Type
EDS I Gravis type AD (13000)
EDS IT Mitis type AD (13001)
EDS I11 Hypermobile type AD (13002)
EDS IV Vascular Heterogeneous
IV-A Acrogeric type AD (13005)
IV-B Acrogeric type AR (22535)
IV-C Ecchymotic type AD (13005)
IV-D Others AD (AR?)’
(All forms have defect of type TI1 collagen)
‘The existence of these subtypes unproven.
 Berlin Nosology 585

EDS V X-linked type XL (30520)

EDS VI Ocular-scoliotic type AR (22540)
VI-A Decreased lysyl hydroxylase activity
(VI-B Normal lysyl hydroxylase activity ?)'
EDS VII Arthrochalasis multiplex congenita Heterogeneous
VII-A Structural defect of pro-a 1( I ) AD (13006)
VII-B Structural defect of pro-a 2( 1 ) AD (13006)
(VII-C Procollagen N-Proteinase deficiency ?)' AR (22541)
EDS VIII Periodontitis type AD (13008)
EDS IX Vacant (formerly occipital horn syndrome, or X-linked
cutis laxa, now recategorized as a disorder of copper
transport) (30415)
EDS X Fibronectin abnormality AR (22531)
EDS XI Vacant (formerly familial joint instability, now recate-
gorized with the familial articular hypermobility syn-
dromes) (14790)

Cardinal manifestations
Skin-hyperextensible with soft, velvety, doughy texture
Dystrophic scarring
Easy bruising
Joint hypermobility
Connective tissue fragility
EDS 1 Cardinal manifestations in severe degree
EDS I1 Cardinal manifestations in mild degree
EDS 111 Marked articular hypermobility
Moderate dermal hyperextensibility
Minimal scarring
EDS IV Variable stigmata
Severe bruising, hyperpigmentation and/or scarring
Thin skin with prominent venous plexus
Vascular rupture
Colonic perforation
Characteristic facial appearance
EDS V Cardinal manifestations in moderate degree
X-linked inheritance
EDS VI Cardinal manifestations in severe degree
Eye involvement (microcornea, scleral perforation, retinal detachment)
Scoliosis
EDS VII Cardinal manifestations with marked articular hypermobility
Short stature
Micrognathia
EDS VIII Cardinal manifestations in moderate degree
Aggressive periodentitis, gingival recession, early tooth loss
EDS X Cardinal manifestations but skin texture normal
Petechiae
Striae distensae
Platelet aggregation defect corrected by fibronectin
586 Beighton et al.
4. FAMILIAL ARTICULAR HYPERMOBILITY SYNDROME (14790)
Excludes:
EDS group of disorders, notably EDS I11 (Hypermobile type) and VII (Arthrochalasis
multiplex congenita)
Skeletal dysplasias with joint hypermobility, notably the Larsen syndrome
Cardinal manifestations
Generalized articular hypermobility, with or without subluxation or dislocations
No skin involvement
4- 1 Familial articular hypermobility, uncomplicated type AD/AR
4-2 Familial articular hypermobility, dislocating type (formerly EDS AD
XI, familial joint instability syndrome)
(The basic defect in these disorders is unknown.)

5. SKELETAL DYSPLASIAS WITH PREDOMINANT JOINT LAXITY

5- 1 Larsen Syndrome Mild form: AD (1 5025)
Severe form: AR (24560)
Cardinal manifestations:
Joint laxity, especially at the knees
Flattened nasal bridge
Short stature
Broad terminal phalanges
Radiographic changes:
Supernumerary ossification centres
in the carpus and calceneus
5-2 Desbuquois Syndrome AR (heterogeneous?)
Cardinal manifestations:
Joint laxity
Short stature
Prominent eyes
Broad terminal phalanges
Supernumerary phalanges
Radiographic characteristics:
Supernumerary carpal ossification centres
Prominent lesser trochanter of femur
5-3 Spondyloepimetaphysl Dysplasia With Joint
Laxity (SEMDJL) AR (27164)
Clinical manifestations:
Gross joint laxity with progressive spinal mal-alignment and multiple dislocations
Dwarfism
Characteristic facial appearance
Variable cardiac defects and palatal clefts
Radiographic changes:
Skeletal dysplasia with changes in the vertebrae, epiphyses, and metaphyses
Skeletal dysplasia with changes in the verte-
brae, epiphyses, and metaphyses

6. CUTISLAXA
Excludes:
Ehlers-Danlos syndrome (syn. cutis hyperelastica)
 BerlinNosology 587

Ehlers-Danlos syndrome (syn. cutis hyperelastica)

Cutis laxa with joint mobility and developmental delay
Occipital horn syndrome (formerly EDS IX, X-linked cutis laxa)
Cardinal manifestations:
Loose skin folds
Characteristic “mournful” face with beaked nose and long upper lip
Variable systemic involvement (pulmonary emphysema, diverticula of the gut, hernia)
Joints not hypermobile
Skin not fragile
6-1 Cutis laxa, benignform AD (12370)
6-2 Cutis laxa, severe form AR (21910)

7. PSEUDOXANTHOMA ELASTICUM
Cardinal changes:
Skin-yellow infiltrated lesions, maximal in the flexures
Eyes-angioid streaks, retinal hemorrhage
Cardiovascular-calcification of the media of medium-sized arteries, with progressive
occlusion and occasional rupture
7- 1 fseudoxanthoma elasticum (fXE)-AD form (probably heterogeneous) (17785)
7-2 Pseudoxanthoma elasticum (fXE)-AR form (probably heterogeneous) (26480)
Elastic fibres are characteristically fragmented and calcified in skin biopsy specimens but
the basic defect is unknown.

8. EPIDERMOLYSIS BULLOSA (EB)

Epidermolysis bullosa is the descriptive term used for the mechano-bullous genoderma-
toses. The 26 subtypes are characterized by traumatically induced blistering of the skin,
while the nails and mumus membranes are variably affected.
EB is traditionally divided into three major subgroups depending on the presence or
absence of scarring of the skin and on the ultrastructural changes. These are:
Simplex (nonscarring)
Atrophicans (nonscarring with skin atrophy)
Dystrophica (scarring)
The dystrophica subgroups are inherited connective tissue disorders; some of these
conditions are associated with absence or abnormality of type VII collagen. The
atrophicans forms, with basement membrane defects, may turn out to be disorders of
connective tissue, but at present their status is uncertain. In the simplex forms, the defect
is in the epidermis, and they cannot, therefore, be regarded as connective tissue disorders.
The 8 dystrophic subtypes are listed below. In accordance with conventional terminology,
eponyms have been retained.
8- 1 Epidermolysis Bullosa Dystrophica, Cock yne-Touraine AD (13180)
8-2 Epidermolysis Bullosa Dystrophica, Pasini AD (13175)
8-3 Epidermolysis Bullosa Dystrophica, Pretibial type AD (13185)
8-4 Epidermolysis Bullosa Dystrophica, Hallopeau Siemens (local- AR (22660)
ized and mutilans forms)
8-5 Epidermolysis Bullosa Dystrophica Inversa AR (22645)
8-6 Epidermolysis Bullosa Dystrophica, Winship AR
8-7 Epidermolysis Bullosa Dystrophica, Fine AR
8-8 Epidermolysis Bullosa Progressiva AR (22650)
588 Beighton et al.
9. HERITABLE DISORDERS OF CONNECTIVE TISSUE SECONDARY TO
METABOLIC DEFECTS
9- 1 Alcaptonuria (Homogentisic acid oxidase deficiency) AR (20350)
9-2 Homocystinuria AR
Pyridoxine responsive form (23620)
Pyridoxine unresponsive form (23625)

10. DISORDERS OF COPPER TRANSPORT

10-1 Occipital Horn Syndrome (formerly EDS IX, X-linked cutis laxa) XL (30415)
Diagnostic clinical criteria:
Skin lax and mildly hyperextensible
Hypermobile digits
Bony protuberances of the occiput (evident as bony nubbins in
the first decade)
Limitation of extension of the elbows and knees due to bone
modeling defects
Carpal bone coalescences
Short clavicles
Bladder diverticulae
Osteomalacia
Chronic diarrhea (variable)
Postural hypotension (occasional)
Diagnostic biochemical criteria:
Moderate decrease in serum copper and ceruloplasmin levels
Excess copper and increased 64Cuaccumulation (attached to
metallothionein) in cultured fibroblasts
10-2 Menkes Syndrome XL (30940)
(Classical and mild forms)
Diagnostic clinical criteria:
(Classical and &Id forms)
Diagnostic clinical criteria:
Lax skin
Hypermobile joints
Severe brain dysfunction
Vascular rupture
Abnormal hair
Diagnostic biochemical criteria:
Decreased serum copper and ceruloplasmin levels
Excess copper and increased 64Cuaccumulation (attached to
metallothionein) in cultured fibroblastic cells

1 1. OSTEOCENESIS IMPERFECTA
Information concerning biochemical and molecular defects in 01 is accumulating rapidly
but a nosology based on a synthesisof these factors, together with clinical and genealogical
data is not yet possible. The current classification of 01 on a basis of clinical and
radiological changes is given below.
01 type I Osseous fragility (variable from minimal through AD (16620)
moderately severe), distinctly blue sclerae (at all (heterogeneous)
ages), presenile hearing loss
 BerlinNosology 589

01 type I1 Lethal perinatal 0 1 . Extremely severe osseous fragil-

ity, stillbirth or neonatal death
Sub-group A) Radiographs show broad, crumpled AD (16621)
long bones and broad ribs with continuous beading new mutation
Sub-group B) Radiographs show broad, crumpled AR? (25940)
long bones, ribs show discontinuous beading or are
not beaded
Sub-group C) Radiographs show thin, fractured long AR? (25940)
bones and thin, beaded ribs
0 1 type IT1 Moderately severe to severe osseous fragility, normal AR (25942)
sclerae (sometimes blue in infancy), variable but se-
vere deformity of long bones and spine, stunted stat-
ure. Generally nonlethal in the newborn infant
0 1 type IV Osseous fragility with normal sclerae (blue in infan- AD (16622)
cy), variable deformity of long bones and spine
Note: i. The value of opalescent dentin (DI) for subcate-
gorization is uncertain.
ii. In families with 01-1, linkage has been demon-
strated with the pro-a l(1) (COLlAl) and pro-cu
2(1) (COLlA2) collagen gene loci. In a few fam-
ilies with 01-IV, linkage with pro-a 2( 1)
(COLlA2) has been recorded.

12. MISCELLANEOUS INHERITED CONNECTIVE TISSUE DISORDERS

12-1 Cutis laxa with joint hypermobility and developmental AR (2 1920)
delay excludes Ehlers-Danlos syndrome, classical cutis
laxa, and X-linked cutis laxa (now occipital horn syn-
drome)
12-2 Wrinkly skin syndrome AR (27825)
Diagnostic criteria:
Joint laxity
Low birth weight
Wrinkled skin over hands and feet
12-3 Dermatojbrosis lenticularis disseminata with osteopoiki- AD (1 6670)
h i s (Buschke-Ollendorff syndrome)
12-4 Familial cutaneous collagenoma AD/AR (11525)
12-5 Keloid formation AD? (14810)
12-6 Elastosis perforans serpiginosa AD? (13010)
12-7 Reactive perforating collagenosis AR? (21670)

ACKNOWLEDGMENTS
We thank Gillian Shapley for typing the manuscript with her usual enthusiasm and
efficiency. This research was supported by grants from the South African Medical
Research Council, the Mauerberger Foundation, the Harry Crossley Foundation, and the
University of Cape Town Staff Research Fund.
590 Beighton et al.

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5. SKELETAL DYSPLASIAS WlTH PREDOMINANT JOINT LAXITY

LARSEN SYNDROME
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6. CUTlSIAXA
Beighton P (1972): The dominant and recessive forms of cutis laxa. J Med Genet 9216-222.
Fitzsimmons JS, Fitzsimmons EM, Guibert PR, Zaldua V, Dodd KL (1985): Variable clinical presentation of
cutis laxa. Clin Genet 28:284-295.
Goltz RW, Hult AM, Goldfarb M, Gorlin RJ (1965): Cutis laxa. Arch Dermatol92:373-387.
Weir EK, Joffe HS, Blaufuss AH, Beighton P (1977): Cardiovascular abnormalities in cutis laxa. Eur J Cardiol
5:255-261.
Brown FR 111, Holbrook KA, Byers PH, Steward D, Dean J, Pyeritz RE (1982): Cutis laxa. Johns Hopkins Med
J 150148-153.

7. PSEUWXANTHOMA ELASTICUM
Goodman RM, Smith EW, Paton D, Bergman RA, Siege1 CL, Ottesen OE, Shelley WM, Pusch AL, McKusick
VA ( 1 963): Pseudoxanthoma elasticum, a clinical and histopathological study. Medicine 42:297-334.
Pope FM ( I 974): Autosomal dominant variants of pseudoxanthoma elasticum. J Med Genet 11:152-157.
Pope FM (1974): Two types of autosomal recessive pseudoxanthoma elasticum. Arch Dermatol 110:209-212.
Pope FM (1975): Historical evidence for the genetic heterogeneity of pseudoxanthomaelasticum. Br J Dermatol
92493-509.
Viljoen DL, Beighton P, Mabin T,Woods K, Saxe N, Bonafede P (1984): Pseudoxanthoma elasticum in South
Africa: Genetic and clinical implications. S Afr Med J 66:813-816.

8. EPIDERMOLYSIS BUL.MSA
Anton-Lamprecht I, Hashimoto I (1976): Epidermolysis bullosa dystrophica dominans (Pasini): A primary
structural defect of the anchoring fibrils. Hum Genet 32:69-76.
Bauer EA, Eisen AZ (1978): Recessive dystrophic epidermolysis bullosa: Evidence for increased collagenase as a
genetic characteristic in cell culture. J Exp Med 148:1378-1387.
Briggaman RA, Wheeler CE (1 975): Epidermolysis bullosa dystrophica recessiva: A possible role of anchoring
fibrils in the pathogenesis. J Invest Dermatol 65:203-211.
Heagerty AHM, Kennedy AR, Gunner DB, Eady RAJ (1986): Rapid prenatal diagnosis and exclusion of
epidermolysis bullosa using novel antibody probes. J Invest Dermatol 86603405.
Gedde-Dahl T Jr, Anton-Lamprecht I (1983): Epidermolysis bullosa. In Emery AEH, Rimoin DL (eds):
“Principles and Practice of Medical Genetics,” Vol 1. Edinburgh: Churchill Livingstone.
Winship I (1986): Epidermolysis bullosa in South Africa. S Afr Med J 69:743-746.

9. HERITABLEDISORDERS OF CONNECIlVE TISSUE SECONDARYTO METABOLJC DEFECTS

9.1 Alcaptonuria
Christensen K, Manthorpe R (1983): Alkaptonuria and ochronosis: A survey and 5 cases. Hum Hered
33:14&144.
LaDu BN (1972): Alcaptonuria. In Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown M
(eds):“The Metabolic Basis of Inherited Disease,” 4th ed. New York McGraw-Hill, pp 268-282.
Srsen S, Cisarik F, Pasztor L, Harmecko L (1978): Alkaptonuria in the Trencin district of Czechoslovakia. Am J
Med Genet 2:159-166.
Srsen S (1979): Alkaptonuria. Johns Hopkins Med J 145:217-226.
9.2 Homocystinuria
Hill-Zobel RL, Pyeritz RE, Scheffel U, Malpica 0, Engin S, Camargo EE, Abbott MH, Guilarte TR, Hill J,
McIntyre PA, Murphy EA, Tsan M-F (1 982): Kinetics and biodistribution of ”‘In-labeled-platelets in
homocystinuria.N Engl J Med 307:781-786.
Mudd SH, Levy HL (1983): Disorders of transsulfulation. In Stanbury JB, Wyngaarden JB, Fredrickson DS,
Goldstein JL, Brown M (eds): “The Metabolic Basis of Inherited Disease,” 5th ed. New York:
McGraw-Hill, pp 522-559.
Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GHJ, Bromberg IL,
Cerone R,Fowler B, Grobe H.Schmidt H, Schweitzer L (1985): The natural history of homocystinuria
due to cystathionine beta-synthase deficiency. Am J Hum Genet 361-31.
 Berlin Nosology 593

10. DISORDERS OF COPPER TRANSPORT

10.1 Occipital Horn Syndrome
Byers PH, Siege1 RC, Holbrook KA, Narayanan AS, Bornstein P, Hall JG (1980): X-linked cutis laxa. N Engl J
Med 303:6165.
Peltonen L, Kivaniemi H, Palotie A, Horn N, Kaitila I, Kivirikko K (1983): Alterations in copper and collagen
metabolism in the Menkes syndrome and a new subtype. of the Ehlers-Danlos syndrome. Biochemistry
2261464163.
Satoris DJ, Luzzatti L, Weaver DD, MacFarlane JD, Hollister DW, Parker BR (1984): Type IX Ehlers-Danlos
syndrome. Radiology 152:665470.
10.2 Menkes Syndrome
Danks DM (1986): Of mice and men, metals and mutations. J Med Genet 23:99-106.
Danks DM (1983): Hereditary disorders of copper metabolism in Wilson’s disease and Menke’s disease. In
Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown M (eds): “The Metabolic Basis of
Inherited Disease,” 5th ed. New York McGraw-Hill, pp 1251-1268.
Danks DM, Camakaris J (1983): Mutations affecting trace elements in humans and animals: A genetic
approach to the understanding of trace elements. Adv Hum Genet 13:149-216.
Menkes JH (1972): Kinky hair disease. Pediatrics 50:181-182.

1 1. OSTEOGENESIS IMPERFECTA
Beighton P, Versfeld GA (1985): On the paradoxically high relative prevalence of osteogenesis imperfecta Type
I11 in the Black population of South Africa. Clin Genet 27:39&404.
Levin LS, Brady JM, Melnick M (1980): Scanning electron microscopy of teeth in autosomal dominant
osteogenesis irnperfecta: Support for genetic heterogeneity. Am J Med Genet 5189-199.
Paterson CR, McAllison S, Miller R (1983): Heterogeneity of ostwgenesis imperfecta type I. J Med Genet
20:203-205.
Sillence DO, Senn A, Danks DM (1979): Genetic heterogeneity in osteogenesis imperfecta. J Med Genet
16:101-116.
Sillence DO, Barlow KK, Garber AP, Hull JG, Rimoin DL (1984): Osteogenesis imperfecta type 11. Delineation
of the phenotype with reference to genetic heterogeneity.Am J Med Genet 17:407423.
Sillence DO, Barlow KK, Cole WG, Dietrich S, Garber AP, Rimoin DL (1986): Osteogenesis imperfecta Type
111. Delineation of the phenotype with reference to genetic heterogeneity.Am J Med Genet 23:821-832.
Sykes B, Ogilvie D, Wordsworth P, Anderson J, Jones N (1986): Osteogenesis imperfecta is linked to both type I
collagen structural genes. Lancet 2:69-72.
Tsipouras P, B$rresen A-L, Dickson LA, Berg K, Prockup DJ, Ramirez F (1984): Molecular heterogeneity in
the mild autosomal dominant forms of osteogenesis imperfecta. Am J Hum Genet 36:1172-1179.
Wallis G, Beighton P, Boyd C, Mathew CG (1986): Mutations linked to the pro-cu 2(I) collagen gene are
responsible for several cases of osteogenesis imperfecta type I. J Med Genet 23:411-416.

12. MISCELLANEOUS INHERITED CONNECTIVE TLSSUE DISORDERS

12.1 Cutis laxa withjoint hypermobility and developmental delay
Agha A, Sakati MC, Higginbottom KL, Jones KL Jr, Bay C, Nyhan WL (1978): Two forms of cutis laxa
presenting in the newborn period. Acta Paediatr Scand 67:775-780.
Sakati NO, Nyhan WL, Shear CS, Kattan H, Akhtar M, Bay C, Jones KL, Schackner L (1983): Syndrome of
cutis laxa, ligamentous laxity and delayed development. Pediatrics 72:85&856.
Dank DM, Rogers JG (1985): Cutis laxa with delayed development. Aust Paediatr J 21:281-283.
12.2 Wrinkly Skin Syndrome
Gazit E, Goodman RM, Bat-Miriam Katznelson M, Rotem Y (1973): The wrinkly skin syndrome: A new
heritable disorder of connective tissue. Clin Genet 4:186-191.
12.3 Dermatofbrosis lenticularis disseminata with osteopoikilosis (Buschke-Ollendorff syndrome) AD
Lagier R, Mbakop A, Bigler A (1984): Osteopoikilosis: A radiological and pathological study. Skeletal Radio1
11:161-168.
Verbov J, Graham R (1986): Buschke-Ollendorf syndrome: Disseminated dermatofibrosis ostwpoikilosis. Clin
Exper Dermatol 11:17-26.
12.4 Familial cutaneous collagenoma
Sacks HN, Crawley IS, Ward JA, Fine RM (1980): Familial cardiomyopathy,hypogonadism and collagenoma.
Ann Intern Med93:813-817.
Uitto J, Santa-Cruz DJ, Eisen A 2 (1979): Familial cutaneous collagenoma: Genetic studies on a family. Br J
594 Beighton et al.
Dermatol I0 1:185-195.
12.5 Keloid formation
Bloom D (1956): Heredity of keloids: Review of the literature and report of a family with multiple keloids in five
generations. NY J Med 56:511--519.
12.6 Elastosis perforans serpiginosa
Ayala F, Donofrio P (1983): Elastosis perforans serpiginosa: Report of a family. Dermatologica 167:lll.
1 2.7 Reacrive perforating collagenosis
Kanan MW (1974): Familial reactive perforating collagenosis and intolerance to cold. Br J Dermatol
91:405414.
Mehregan AH, Schwartz OD, Livingood CS (1 967): Reactive perforating collagenosis. Arch Dermatol
96~271-282.
Nair BKH, Sarojini PA, Basheer AM, Nair CHK (1974): Reactive perforating collagenosis. Br J Dermatol
9 1 :399403.

Edited by James F. ReynoIds