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Patau Syndrome
Updated: Oct 04, 2017
Author: Robert G Best, PhD, FACMG; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG

Overview

Background
Patau syndrome is the least common and most severe of the viable autosomal trisomies. Median survival is fewer than 3 days.
First identified as a cytogenetic syndrome in 1960, Patau syndrome is caused by an extra copy of chromosome 13, a medium-
length acrocentric chromosome.

Many of the clinical features widely vary; however, severe mental deficiency is a consistent feature in children born with Patau
syndrome. Holoprosencephaly, polydactyly, flexion of the fingers, rocker-bottom feet, facial clefting, neural tube defects, and
heart defects are also frequent clinical features. Patau syndrome is generally recognized at birth by the presence of structural
birth defects and poor neurologic performance.

Pathophysiology
Patau syndrome is caused by the presence of an extra copy of chromosome 13, generally present at conception and
transmitted to every cell in the body. Although the exact mechanisms by which chromosomal trisomies disrupt development are
unknown, considerable attention has been paid to trisomy 21 as a model system for the autosomal trisomies.[1]

Normal development requires 2 (and only 2) copies of most of the human autosomal genome; the presence of a third copy of an
autosome is generally lethal to the developing embryo. Therefore, trisomy 13 is distinctive in that it is one of only 3 autosomal
trisomies for which development can proceed to live birth. In fact, trisomy 13 is the largest autosomal imbalance that can be
sustained by the embryo and yet allow survival to term. Complex physiologic structures, such as those found in the CNS and
heart, appear to be particularly sensitive to chromosomal imbalance, either through the actions of individual genes or by the
destabilization of developmental processes involving many genes in concert.

Epidemiology
Frequency
United States

Incidence of Patau syndrome is approximately 1 case per 8,000-12,000 live births. Significant racial or geographic differences in
frequency are not evident, although a well-known association is recognized between Patau syndrome and increased maternal
age, an association common to all autosomal trisomies in fetuses that survive to term.

International

A study by Springett et al of 25 population-based registries in 16 European countries found the incidence of trisomy 13 to be 1.9
per 10,000 total births.[2]

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Mortality/Morbidity

Median survival age for children with Patau syndrome is 2.5 days, with only one in 20 children surviving longer than 6 months.
However, some children survive into their teens and seem to fare better than might be expected based on reports from those
who die in the perinatal period. A multi-state, population-based study by Meyer et al reported the 5-year survival rate for trisomy
13 to be 9.7%, with the lowest mortality rates found among females and the offspring of non-Hispanic black mothers.[3] Reports
of adults with Patau syndrome are rare.

Holoprosencephaly, a frequent brain malformation associated with Patau syndrome, is associated with severe neurological
impairment; development of the structural features of the midface is disrupted when holoprosencephaly is present. Serious
cardiac anomalies are often present.

In the aforementioned study by Springett and colleagues, of 240 live-born infants with trisomy 13, the prevalence of anomalies
was as follows[2] :

Cardiac anomalies: 57%

The most common causes of death in Patau syndrome are cardiopulmonary arrest (69%),[4] congenital heart disease (13%),
and pneumonia (4%). Survivors with Patau syndrome exhibit severe mental retardation and developmental delays and are at
increased risk for malignancy. Infants who survive the neonatal period have an average length of stay in a neonatal ICU of 10.8
days.

A retrospective cohort study by Dotters-Katz et al found that the risk of certain morbidities was higher in women with a trisomy
13 pregnancy than in those with a non–trisomy 13 pregnancy, with the likelihood of gestational hypertensive disorder (GHD)
being 6.3 times greater and the risk for preeclampsia with severe features being 12.5 times higher. In addition, women with a
trisomy 13 pregnancy who had a GHD were 14.1 times more likely to deliver before 37 weeks’ gestation and 11.2 times more
likely to deliver before 32 weeks’ gestation.[5]

Sex

The sex ratio at birth is slightly skewed toward females, presumably because of decreased survival among males, with
continued skewing of the ratio further toward females as these children age.

Age

Patau syndrome is expressed prenatally and is fully evident at birth. A significant number of cases that are trisomic for
chromosome 13 end in spontaneous abortion, fetal demise, or stillbirth.[6] The mortality rate is very high among neonates.
Children who survive the neonatal period continue to express developmental delays and exhibit a declining developmental
quotient over time. This decline does not result from loss of developmental milestones but instead reflects a worsening
developmental lag compared with other children. A report on a group of 21 individuals with Patau syndrome (3 mosaic and 18
nonmosaic) who survived past age 5 years showed the oldest to be aged 21 years.

Presentation

History
See the list below:

Newborns with Patau syndrome typically present in the neonatal period with low Apgar scores and may have the
following conditions:

Cleft lip

Cleft palate

Polydactyly (postaxial)

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Microcephaly

Rocker-bottom feet

Microphthalmia

Scalp defects (cutis aplasia)

Omphalocele

Hernias

Neural tube defects

Stillbirth and in utero fetal demise are common pregnancy outcomes. Patients with Patau syndrome may be small for
gestational age (SGA), but it is not uncommon for them to be normally sized at birth.

Physical
See the list below:

Cardiac defects occur in 80% of cases, accompanied by the following conditions:

Patent ductus arteriosus

Ventricular septal defect

Atrial septal defect

Dextrocardia

Holoprosencephaly, in which the brain does not divide completely into halves, is often present and is generally signaled
by the presence of midline facial defects. Facial defects include the following:

Hypotelorism

Microphthalmia

Anophthalmia

Absent or malformed nose or proboscis

Severe clefting of the lip and/or palate

The clinical phenotypes of Patau syndrome and Edwards syndrome may seem similar to physicians who do not
frequently encounter these syndromes.

Capillary hemangiomatas and polycystic kidneys or other renal malformations have been reported.

Causes
See the list below:

Although specific etiologic factors have not been identified, a significant association is recognized between Patau
syndrome and increased maternal age.

Aneuploidy is most often the result of nondisjunction during maternal meiosis I.

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DDx

Diagnostic Considerations
These include the following:

Edwards syndrome

Partial duplication of 13q

Pseudotrisomy 13 (holoprosencephaly-polydactyly syndrome)

Differential Diagnoses
Smith-Lemli-Opitz Syndrome

Workup

Workup

Laboratory Studies
See the list below:

Immediately obtain conventional cytogenetics for any child or neonate with suspected Patau syndrome, unless
cytogenetic diagnosis has been made prenatally. Patau syndrome may occur as a freestanding trisomy of chromosome
13 or, more rarely, as a Robertsonian translocation with an extra copy of chromosome 13 attached to another acrocentric
chromosome (eg, 13-15, 21, 22) or as a structural chromosome abnormality wherein only a part of chromosome 13 is
duplicated. Perform parental blood chromosome studies in the event that a Robertsonian translocation or other structural
chromosome abnormality is found because recurrence risks may be markedly different for freestanding trisomy versus
structural rearrangements.

Antecedents to the prenatal diagnosis of Patau syndrome include abnormal first or second trimester aneuploidy
screening and abnormal prenatal ultrasonography findings, including birth defects or growth restriction. One or more of
these often precedes cytogenetic analysis using chorionic villous sampling (10-13 weeks' gestation) or amniocentesis (15
weeks' gestation or later) in an effort to obtain a small piece of placental tissue or amniocytes from within amniotic fluid,
respectively. Newer techniques of noninvasive prenatal testing using cfDNA from maternal blood sample are very
promising for having high sensitivity and specificity to detect aneuploidy prenatally. Positive predictive values also appear
to be much higher than for standard prenatal aneuploidy screening.[7]

In addition to conventional cytogenetics, fluorescent in-situ hybridization (FISH) on interphase cells could be used
to obtain a more rapid diagnosis. Cytogenetic analysis is a necessary step in the prenatal diagnosis of Patau
syndrome.

Caveats concerning the limitations of aneuploidy screening in cases of Patau syndrome are warranted. Second
trimester screening, which uses maternal serum alpha fetoprotein (MSAFP), human chorionic gonadotropin
(hCG), unconjugated estriol, and inhibin, is often insensitive. A significant number of cases can be detected
through the use of first trimester screening (ie, ultrasonography measurement of the nuchal translucency,
pregnancy associated plasma protein A [PAPPA], and some form of hCG [usually the free circulating form]).

Birth defects identified in fetuses with trisomy 13 include but are not limited to abnormalities of the CNS, cardiac
defects, facial defects, growth restriction, holoprosencephaly, and renal abnormalities.

Mosaicism for trisomy 13 is associated with a milder degree of severity, with the mildest expression typically in the lowest
levels of mosaicism. Higher levels of mosaicism are more closely associated with full constitutional trisomy. Because of
the possibility of different levels of mosaicism in different tissues, no level of mosaicism can be presumed benign.

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Imaging Studies
See the list below:

Initiate appropriate imaging studies when holoprosencephaly or cardiac or renal anomalies are clinically suspected.

Because of the high frequency of structural defects, perform cardiac evaluations on patients with Patau syndrome who
survive the neonatal period.

Treatment

Medical Care
All patients diagnosed prenatally with a fetus affected by Patau syndrome should be offered a consultation with a care provider
skilled in delivering serious information who is knowledgeable about recurrence risk, screening, and diagnostic testing options
for future pregnancies.[8] Although a geneticist or genetics counselor is an ideal source and may be best suited for exploring
family history, an experienced maternal fetal medicine physician or properly trained obstetrician may provide requisite
information especially in regions of the United States, where the amount geneticists and genetic counselors is inadequate.
Specific information related to the management of an ongoing pregnancy should be discussed during this consultation.

Once a diagnosis of Patau syndrome is made, pregnancy management varies according to the gestational age at diagnosis.

At previable gestational ages, the option of pregnancy termination should be among those discussed. The gestational age limits
for this procedure are state-specific and subject to the training and skill of the physician available to perform the pregnancy
termination.

When patients choose not to proceed with pregnancy termination or when the pregnancy has progressed to a viable gestational
age such that pregnancy termination is no longer an option (except in rare locations throughout the United States), attention
should be focused on whether the labor should be induced or spontaneous. If the labor is to be induced, determine the
appropriate gestational age. Due to the physical stresses of pregnancy compounded by the emotional stress of carrying a fetus
with a lethal condition, or because of the identification of medical conditions (eg, preeclampsia) that may complicate any
pregnancy, labor induction may be considered.

Tocolysis (medical management to reduce uterine contractions) in an effort to prevent preterm birth is not a reasonable option
due to the lethal nature of this condition. Cesarean delivery for fetal indications is not recommended due to the lethal nature of
this condition.

Focused discussions directed at neonatal resuscitation efforts should be held in advance of labor. These discussions should
include a discussion of neonatal procedures for resuscitation, the cost of these measures, and alternatives to aggressive
resuscitation. Including a neonatologist in these discussions is often advisable. Clear documentation of these discussions is
warranted. When delivery is planned in a hospital setting, labor and delivery nurses, obstetric care providers, and pediatric and
neonatal attendants should be informed of the patient’s wishes for her child.

Pregnancy management of a child with a lethal condition can be complicated by a lack of available resources. In addition to
having a wealth of experience in dealing with grieving patients, some delivering hospitals are vastly more experienced in the
management of pregnancies complicated by known lethal fetal birth defects. For this reason, the authors recommend that, when
possible, babies with Patau syndrome should be delivered at such centers.

Surgical Care
Surgical interventions are generally withheld for the first few months of life because of the high mortality rates of babies with
Patau syndrome. Carefully weigh decisions about extraordinary life-prolonging measures against the severity of the neurologic
and physical defects that are present and the likelihood of postsurgical recovery or prolonged survival.[9]

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Consultations
Referral to a geneticist or genetic counselor is important for appropriate counseling regarding recurrence risks, etiology,
prognosis, and the availability of local area resources for support.

Recurrence risks differ based on the details of the chromosome abnormality and the mother's age. In general, for freestanding
trisomy 13, the recurrence risk for trisomy 13 or another clinically viable trisomy (ie, trisomy 21, trisomy 18) is approximately
0.5% above the mother's age-related risk for autosomal trisomies. Recurrence risks for Robertsonian and other structural
rearrangements widely vary; these risks can be as high as 100% in rare cases in which a parental translocation occurs involving
both copies of chromosome 13. Consult a genetic counselor or medical geneticist regarding recurrence risks for structural
rearrangements that involve chromosome 13.

Diet
In a group of 12 survivors with Patau syndrome, 4 were documented as requiring gavage feeding as newborns, and 7 were
bottle-fed. Two children ate and drank with help prior to age 54 months, and feeding by spoon, finger, and cup was reported.

Medication

Medication Summary
Medical literature provides little information on the use of specific drugs to treat Patau syndrome.

Follow-up

Further Outpatient Care

Provide surviving children with Patau syndrome the same care other children receive, including visual assessments,
hearing evaluations by age 6-8 months, and immunizations.[10] Treat health problems according to severity and always
in the best interests of the child.

Specific growth charts are available for monitoring growth of children with Patau syndrome.

Continue monitoring for apneic episodes.

Babies with Patau syndrome are notably irritable.

Older children are at risk of developing scoliosis.

At least one older patient has developed hepatoblastoma.[11]

Inpatient & Outpatient Medications

Prior to dental procedures, administer prophylactic antibiotics for children with cardiac anomalies.

Deterrence/Prevention
See the list below:

In each subsequent pregnancy, offer a prenatal diagnostic study to women who have had a pregnancy with an autosomal
aneuploidy, including trisomy 13, 18, or 21. Such studies are also indicated when either parent is known to carry
structural chromosome abnormalities involving chromosome 13. These recommendations are based on an empiric
recurrence of about 1%.

Prognosis
See the list below:

Prognosis is generally quite poor for the neonate identified with Patau syndrome. Median survival is only 2.5 days; 82%
die within 1 month, and 95% die within 6 months.

Patient Education
See the list below:

Although those who survive Patau syndrome have low educational potential, increased stimulation and interaction are
appropriate to maximize developmental potential.

Inform parents about the Support Organization for Trisomy 18, 13, and Related Disorders (SOFT). This organization, with
state and local chapters throughout the country, is a good resource for information and psychosocial support for parents
and families dealing with this difficult disorder.

Living With Trisomy 13 is another organization with information for families and physicians.

Contributor Information and Disclosures

Author

Robert G Best, PhD, FACMG Professor of Biomedical Sciences and Associate Dean for Faculty Affairs, University of South
Carolina School of Medicine, Greenville

Robert G Best, PhD, FACMG is a member of the following medical societies: American College of Medical Genetics and
Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Coauthor(s)

Anthony Romaine Gregg, MD Associate Professor, Director, Division of Maternal and Fetal Medicine, Medical Director,
Division of Genetics, Medical Director, Genetics Counseling Program, Department of Obstetrics and Gynecology, University of
South Carolina School of Medicine

Anthony Romaine Gregg, MD is a member of the following medical societies: American Association for the Advancement of
Science, American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists,
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American Institute of Ultrasound in Medicine, American Medical Association, American Society of Human Genetics, Central
Association of Obstetricians and Gynecologists, Society for Reproductive Investigation, Society for Maternal-Fetal Medicine,
Society for the Study of Reproduction, Perinatal Research Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-
Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Eric T Rush, MD, FAAP, FACMG Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine;
Clinical Geneticist, Children's Mercy Hospital of Kansas City

Eric T Rush, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American
College of Medical Genetics and Genomics, American College of Physicians, American Society for Bone and Mineral Research

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals, Ultragenyx Pharmaceutical,
and Biomarin Pharmaceuticals<br/>Honoraria for: Alexion Pharmaceuticals, Biomarin Pharmaceuticals.

Chief Editor

Luis O Rohena, MD, MS, FAAP, FACMG Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of
Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of
Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics,
American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Elaine H Zackai, MD Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human
Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior
Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate-Craniofacial Association, American
College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Acknowledgements

Special thanks to Dr. James Stallworth for his contributions to the early manuscript.

References

1. Plaiasu V, Ochiana D, Motei G, Anca I, Georgescu A. Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of
Patau syndrome - Review of 5 cases. Maedica (Buchar). 2010 Jul. 5(3):178-85. [Medline]. [Full Text].

2. Springett A, Wellesley D, Greenlees R, et al. Congenital anomalies associated with trisomy 18 or trisomy 13: A registry-based study
in 16 European countries, 2000-2011. Am J Med Genet A. 2015 Sep 8. [Medline].

3. Meyer RE, Liu G, Gilboa SM, et al. Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study. Am J
Med Genet A. 2015 Dec 10. [Medline].

4. Baty BJ, Jorde LB, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: II. Psychomotor development. Am J Med
Genet. 1994 Jan 15. 49(2):189-94. [Medline].

5. Dotters-Katz SK, Humphrey WM, Senz KL, et al. Trisomy 13 and the risk of gestational hypertensive disorders: a population-based
study. J Matern Fetal Neonatal Med. 2017 Jun 2. 1-5. [Medline].

6. Morris JK, Savva GM. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18. Am J Med Genet A. 2008 Apr
1. 146(7):827-32. [Medline].

https://emedicine.medscape.com/article/947706-print 8/9
30/8/2019 https://emedicine.medscape.com/article/947706-print
7. Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF. DNA sequencing versus standard prenatal aneuploidy
screening. N Engl J Med. 2014 Feb 27. 370(9):799-808. [Medline].

8. [Guideline] American College of Obstetricians and Gynecologists (ACOG). Screening for fetal chromosomal abnormalities.
Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2007 Jan. 11 p. (ACOG practice bulletin; no. 77).
[Full Text].

9. Peterson JK, Kochilas LK, Catton KG, Moller JH, Setty SP. Long-Term Outcomes of Children With Trisomy 13 and 18 After
Congenital Heart Disease Interventions. Ann Thorac Surg. 2017 Jun. 103 (6):1941-9. [Medline].

10. Jaru-Ampornpan P, Kuchtey J, Dev VG, Kuchtey R. Primary congenital glaucoma associated with patau syndrome with long survival.
J Pediatr Ophthalmol Strabismus. 2010 Jun 23. 47 Online:e1-4. [Medline].

11. Shah R, Tran HC, Randolph L, Mascarenhas L, Venkatramani R. Hepatoblastoma in a 15-month-old female with trisomy 13. Am J
Med Genet A. 2014 Feb. 164A(2):472-5. [Medline].

12. Fogu G, Maserati E, Cambosu F, Moro MA, Poddie F, Soro G, et al. Patau syndrome with long survival in a case of unusual mosaic
trisomy 13. Eur J Med Genet. 2008 Jul-Aug. 51(4):303-14. [Medline].

13. Iliopoulos D, Sekerli E, Vassiliou G, et al. Patau syndrome with a long survival (146 months): a clinical report and review of literature.
Am J Med Genet A. 2006 Jan 1. 140(1):92-3. [Medline].

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