Practice Essentials
Patau syndrome, also called trisomy 13, 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. Cytogenetic analysis is a necessary step in the prenatal diagnosis of Patau syndrome. 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. [1]
Signs and symptoms of Patau syndrome
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.
Workup in Patau syndrome
Immediately obtain conventional cytogenetics for any child or neonate with suspected Patau syndrome, unless cytogenetic diagnosis has been made prenatally.
Antecedents to the prenatal diagnosis of Patau syndrome include abnormal first or second trimester aneuploidy screening and abnormal prenatal ultrasonographic findings, including birth defects or growth restriction. In addition to conventional cytogenetics, fluorescent in-situ hybridization (FISH) on interphase cells could be used to obtain a more rapid prenatal diagnosis.
Initiate appropriate imaging studies when holoprosencephaly or cardiac or renal anomalies are clinically suspected.
Because of the high frequency of structural defects in Patau syndrome, perform cardiac evaluations on patients who survive the neonatal period.
Management
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.
Surgical interventions in Patau syndrome are generally withheld for the first few months of life because of the high mortality rates of babies with the condition. 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. [2, 3]
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. [4]
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. [5]
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. [6] Reports of adults with Patau syndrome are rare.
A Western European study by Glinianaia et al estimated that among children with trisomy 13, the survival rates at 4 weeks, 1 year, and 10 years are 34%, 17%, and 11%. [7]
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 [5] :
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Cardiac anomalies: 57%
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Nervous system anomalies: 39%
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Eye anomalies: 30%
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Polydactyly: 44%
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Orofacial cleft: 45%
The most common causes of death in Patau syndrome are cardiopulmonary arrest (69%), [8] congenital heart disease (13%), and pneumonia (4%). Survivors with Patau syndrome exhibit severe intellectual disability 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 study by Ma et al using the Kids’ Inpatient Database found that of 73,107 admissions for congenital heart surgery in patients under age 18 years (for 1997, 2000, 2003, 2006, and 2009), 0.03% were associated with trisomy 13. The investigators also found that the mortality rate for cardiac surgery admissions among patients with trisomy 13 was 14%, compared with 4.5% for all cardiac surgery admissions. [9]
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. [10]
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. [11] 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.
