eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Patau Syndrome

Robert G Best, PhD, FACMG, Director, Department of Obstetrics and Gynecology, Division of Genetics, Professor, University of South Carolina School of Medicine
James Stallworth, MD, Program Director, Associate Professor, Department of Pediatrics, Palmetto Richland Memorial Hospital, University of South Carolina

Updated: Dec 12, 2007

Introduction

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 are highly variable; 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.

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.

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.

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. 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 mid face is disrupted when holoprosencephaly is present. Serious cardiac anomalies are often present. Most common causes of death are cardiopulmonary arrest (69%),¹ 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.

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. 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.

• Pregnant patients aged 35 years or older and patients whose ultrasonographic findings are consistent with increased risk of aneuploidy often elect fetal karyotyping through chorionic villus sampling or amniocentesis. Termination of pregnancy is an option for the patient with a fetus exhibiting trisomy 13 before 24 weeks' gestation.
• If the diagnosis of trisomy 13 is discovered in the prenatal period after 24 weeks' gestation or if the patient elects to continue the pregnancy diagnosed at an earlier gestational age, counseling that discusses the futility of performing a Cesarean delivery for fetal indications is appropriate. Avoid exposing a pregnant woman to the risks of a major operation with little expected benefit to the neonate.

Clinical

History

• 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)
  • Microcephaly
  • Rocker-bottom feet
  • Microphthalmia
  • Scalp defects (cutis aplasia)
  • Omphalocele
  • Hernias
  • Neural tube defects
• Stillbirth and in utero fetal demise are common pregnancy outcomes.

Physical

• 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

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.

Differential Diagnoses

Smith-Lemli-Opitz Syndrome

Other Problems to Be Considered

Edwards syndrome
Partial duplication of 13q

Workup

Laboratory Studies

• 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.
• When Patau syndrome is suspected prenatally (usually because of the presence of ultrasonographic anomalies, history of chromosome abnormalities, or maternal age), trisomy 13 is best identified through conventional cytogenetic study of amniotic fluid, chorionic villi, or fetal blood. If fluorescent in situ hybridization (FISH) on interphase cells is used to obtain a rapid diagnosis, confirm results with conventional cytogenetic methods. Do not make irreversible pregnancy management decisions based solely on FISH results.
  • Second-trimester multiple-marker screening (eg, maternal serum alpha fetoprotein [MSAFP], human chorionic gonadotropin [hCG], unconjugated estriol, inhibin) is not usually sensitive to the presence of Patau syndrome. A significant proportion of cases may be identified through first-trimester multiple-marker testing (eg, ultrasonographic measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPPA], and some form of hCG).
  • Ultrasonographic findings may include increased nuchal translucency, cardiac anomalies, omphalocele, renal anomalies, pyloric stenosis, neural tube defects, and facial clefting.
• 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.

Imaging Studies

• 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

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 neurological and physical defects that are present and the likelihood of postsurgical recovery or prolonged survival.

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

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. 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.

Inpatient & Outpatient Medications

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

Deterrence/Prevention

• 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.

Prognosis

• 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

• 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.

Miscellaneous

Medicolegal Pitfalls

• Recurrence risks to extended family members are increased when Patau syndrome occurs because of structural chromosome abnormalities. The physician should exercise due diligence to evaluate the patient for structural chromosome rearrangements and to offer additional testing to at-risk family members. Recurrence risks for future pregnancies must be addressed in all cases, whether aneuploidy or structural rearrangements are involved.

References

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

2. Barnes AM. Care of the Infant and Child With Trisomy 18 or 13: Medical Problems, Reported treatments and Milestones. 2^nd ed. University of Nebraska Medical Center; 2000.

3. Baty BJ, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet. Jan 15 1994;49(2):175-88. [Medline].

4. Goldstein H, Nielsen KG. Rates and survival of individuals with trisomy 13 and 18. Data from a 10-year period in Denmark. Clinical Genetics. Dec 1988;34(6):366-72. [Medline].

5. 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. Jan 1 2006;140(1):92-3. [Medline].

6. Jones KL. Trisomy 13 syndrome. In: Smith's Recognizable Patterns of Human Malformation. 5th Edition. Saunders/Elsevier; 1997:18-23.

7. Papageorghiou AT, Avgidou K, Spencer K, Nix B, Nicolaides KH. Sonographic screening for trisomy 13 at 11 to 13(+6) weeks of gestation. Am J Obstet Gynecol. Feb 2006;194(2):397-401. [Medline].

8. Pont SJ, Robbins JM, Bird TM, et al. Congenital malformations among liveborn infants with trisomies 18 and 13. Am J Med Genet A. Aug 15 2006;140(16):1749-56. [Medline].

Keywords

Patau syndrome, trisomy 13 syndrome, D1 trisomy syndrome, trisomy D syndrome, severe mental deficiency, viable autosomal trisomy, holoprosencephaly, hypotelorism, microphthalmia, anophthalmia, Edwards syndrome, aneuploidy, Robertsonian translocation, polydactyly, neural tube defects, flexion of the fingers, rocker-bottom feet, facial clefting, trisomy 21, cardiopulmonary arrest, spontaneous abortion, fetal demise, stillbirth, cleft lip, cleft palate, microcephaly, omphalocele, patent ductus arteriosus, ventricular septal defect, dextrocardia

Contributor Information and Disclosures

Author

Robert G Best, PhD, FACMG, Director, Department of Obstetrics and Gynecology, Division of Genetics, Professor, University of South Carolina School of Medicine
Robert G Best, PhD, FACMG is a member of the following medical societies: American Academy of Nanomedicine, American College of Medical Genetics, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Coauthor(s)

James Stallworth, MD, Program Director, Associate Professor, Department of Pediatrics, Palmetto Richland Memorial Hospital, University of South Carolina
James Stallworth, MD is a member of the following medical societies: Alpha Omega Alpha, Ambulatory Pediatric Association, American Academy of Pediatrics, Phi Beta Kappa, Society for Adolescent Medicine, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Elaine H Zackai, MD, Director of Clinical Genetics Center, Professor of Pediatrics, Department of Pediatrics, Division of Human Genetics and Molecular Biology, University of Pennsylvania, Children's Hospital of Philadelphia
Elaine H Zackai, MD is a member of the following medical societies: American College of Medical Genetics, American College of Phlebology, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Robert Anthony Saul, MD, Senior Clinical Geneticist, Greenwood Genetic Center; Clinical Professor, Department of Pediatrics, University of South Carolina
Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pathology and Microbiology, Director, Hattie B Munroe Center for Human Genetics, Chairman, Department of Pediatrics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

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