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Patau Syndrome
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.
More on Patau Syndrome |
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| Treatment & Medication: Patau Syndrome |
| Follow-up: Patau Syndrome |
| References |
| Next Page » |
References
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].
Barnes AM. Care of the Infant and Child With Trisomy 18 or 13: Medical Problems, Reported treatments and Milestones. 2nd ed. University of Nebraska Medical Center; 2000.
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].
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].
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].
Jones KL. Trisomy 13 syndrome. In: Smith's Recognizable Patterns of Human Malformation. 5th Edition. Saunders/Elsevier; 1997:18-23.
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].
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].
Further Reading
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
