Patau Syndrome 

Updated: Sep 03, 2019
Author: Robert G Best, PhD, FACMG; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG 

Overview

Practice Essentials

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. 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]

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.[3]

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.[4]

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.[5] 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[4] :

  • Cardiac anomalies: 57%
  • Nervous system anomalies: 39%
  • Eye anomalies: 30%
  • Polydactyly: 44%
  • Orofacial cleft: 45%

The most common causes of death in Patau syndrome are cardiopulmonary arrest (69%),[6] 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 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.[7]

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.[8]

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.[9] 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)

    • 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.

 

DDx

Diagnostic Considerations

These include the following:

  • Edwards syndrome

  • Partial duplication of 13q

  • Pseudotrisomy 13 (holoprosencephaly-polydactyly syndrome)

Differential Diagnoses

 

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.

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.[10]

In addition to conventional cytogenetics, fluorescent in-situ hybridization (FISH) on interphase cells could be used to obtain a more rapid prenatal 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.

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

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.[11] 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.[2]

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

See the list below:

  • Provide surviving children with Patau syndrome the same care other children receive, including visual assessments, hearing evaluations by age 6-8 months, and immunizations.[12] 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.[13]

Inpatient & Outpatient Medications

See the list below:

  • 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.