Patau Syndrome (Trisomy 13)
Patau syndrome is the third most common autosomal trisomy, with a live birth prevalence of approximately 1 in 7,000 to 1 in 16,000.
Non-dysjunction: The majority (>90%) of cases are due to full trisomy 13 from a meiotic non-dysjunction event, where every cell has an extra copy of chromosome 13 (47, XX, +13 or 47, XY, +13). This is typically a sporadic, non-inherited event, with the risk increasing with advanced maternal age.
Robertsonian translocation: Around 5-10% of cases are due to a Robertsonian translocation, where the extra chromosome 13 is attached to another acrocentric chromosome (most commonly chromosome 14). This form can be inherited, and genetic counselling for parents is essential to assess recurrence risk.
Mosaicism: A small proportion of cases involve mosaicism, where only some cells contain the extra chromosome 13. This can lead to a milder phenotype and a longer life expectancy, as the severity of the condition depends on the ratio of trisomic to normal cells.
Antenatal and Postnatal Diagnosis
Antenatal screening for Trisomy 13 (and 18) is offered in the UK as part of the NHS Fetal Anomaly Screening Programme.
Combined Test: This is offered between 10 and 14 weeks of gestation and combines a blood test (for PAPP-A and free ß-hCG) with a nuchal translucency (NT) measurement from an ultrasound scan.
NIPT: Non-invasive prenatal testing (NIPT), a blood test that analyses cell-free fetal DNA, is offered as a more accurate secondary screening test in cases with a higher-chance result from the combined test.
Diagnostic Testing: Following a higher-chance screening result, definitive diagnosis is made via invasive procedures such as chorionic villus sampling (CVS) or amniocentesis, which allow for a full karyotype analysis or a chromosomal microarray. These methods are essential for distinguishing between full trisomy, mosaicism, and translocations.
Postnatal Diagnosis: If a prenatal diagnosis has not been made, Patau syndrome is suspected clinically at birth based on the constellation of congenital anomalies. The diagnosis is confirmed by cytogenetic analysis of a blood sample.
Clinical Anomalies
The clinical presentation is severe, often with intrauterine growth restriction (IUGR). Over 80% of cases have a congenital heart defect.
Craniofacial and Neurological: The key features are often midline defects. These include microcephaly, a sloping forehead, and holoprosencephaly (failure of the forebrain to divide into two hemispheres). Other features include micropthalmia or anophthalmia, cleft lip and/or palate, and ear malformations. Patients experience severe global developmental delay. Seizures are common.
Musculoskeletal: Polydactyly (extra digits) is a highly characteristic feature, along with clenched hands and rocker-bottom feet.
Cardiac: The most common congenital heart defects include VSD, ASD, and PDA, as well as more complex anomalies like Tetralogy of Fallot.
Other: Renal anomalies (e.g., polycystic kidneys), omphalocele, and scalp defects (cutis aplasia) are also frequently seen.
Management, Prognosis, and Recent Developments
The prognosis remains poor, with a high rate of intrauterine death and stillbirth. Historically, it was reported that over 90% of live-born infants died within the first year of life. However, recent medical literature highlights a shift in the approach to care, moving away from comfort-only care to a more nuanced, shared decision-making model.
Evolving Prognosis: Recent studies, particularly from the American Academy of Pediatrics (AAP), show that a greater number of children with Trisomy 13 are living longer due to more aggressive and a proactive approach to medical and surgical interventions. While the median survival is still short (often days to weeks), a small but increasing percentage of children survive beyond their first year, and some have lived into their teens.
Shared Decision-Making: There is increasing emphasis on sensitive counselling and shared decision-making with families. Rather than a blanket “no intervention” approach, the focus is now on discussing the potential for life-prolonging interventions, such as cardiac surgery or gastrostomy tube placement, and aligning the care plan with the family’s values and goals. The decision to pursue such interventions is no longer based solely on the Trisomy 13 diagnosis but is considered on an individual, patient-by-patient basis.
Supportive Care: Management remains primarily supportive and palliative. However, this now includes a wide spectrum of care, from basic comfort care to intensive medical support and surgical correction of life-threatening anomalies. Care is best delivered by a multidisciplinary team.
Quality of Life: Importantly, despite profound physical and developmental challenges, parents consistently report a high quality of life for their children with Trisomy 13.
UK Support: UK-based charities like SOFT UK (Support Organisation for Trisomy 13/18) and ARC (Antenatal Results and Choices) provide crucial support and information to families and professionals.