Patau Syndrome

Patau syndrome (trisomy 13) is a chromosomal disorder with holoprosencephaly, midline defects, polydactyly and severe disability, with high early mortality. It affects about 1 in 10000 to 16000 live births.

Pathophysiology. Most cases are full trisomy 13 from maternal meiotic non-disjunction, with higher risk at older maternal age. About 20% have a Robertsonian translocation or mosaic form.

Excess dosage of chromosome 13 genes disrupts midline brain, face, eye and limb development.

Most infants die in the first weeks, and the minority who survive the first year have profound disability.

• Holoprosencephaly with microcephaly
• Cleft lip and palate, midface hypoplasia, hypotelorism or cyclopia
• Microphthalmia, coloboma
• Postaxial polydactyly of the hands and feet, clenched hands, rocker bottom feet
• Scalp defects (cutis aplasia)
• Congenital heart disease (in about 80%), renal anomalies, omphalocele, and cryptorchidism
• Apnoea, hypotonia and seizures
• Profound developmental delay
• Deafness and visual impairment

• Prenatal screening: increased risk on screening or cell free DNA testing, and ultrasound findings (holoprosencephaly, cleft lip, polydactyly, heart defects).
• Prenatal diagnosis: amniocentesis or chorionic villus sampling with karyotype or microarray.
• Postnatal confirmation: rapid FISH or quantitative PCR, followed by karyotype to define the type.
• Imaging: cranial ultrasound or MRI, echocardiography, and renal and abdominal ultrasound.
• Parental karyotype when a translocation is found.

Differential diagnosis.

• Edwards syndrome (trisomy 18)
• Meckel-Gruber syndrome
• Smith-Lemli-Opitz syndrome
• Holoprosencephaly of other cause (SHH and other gene variants)
• Triploidy
• Oral-facial-digital syndromes

• Individualised care planning: discuss prognosis and options with parents, and choose between comfort focused care and active treatment, with palliative care involved from diagnosis and revisited as the child's condition evolves.
• Respiratory support: oxygen, airway positioning, and ventilatory support if chosen. Caffeine citrate 20 mg/kg loading dose then 5 to 10 mg/kg daily may help central apnoea.
• Feeding: nasogastric or gastrostomy feeding, with surgery for cleft lip and palate when the child is stable. Treat reflux with omeprazole 0.7 to 1 mg/kg daily.
• Seizures and neurological care: levetiracetam 10 mg/kg twice daily increasing to 30 mg/kg twice daily, and treatment of infantile spasms (prednisolone 40 to 60 mg daily or vigabatrin 50 mg/kg daily increasing to 100 to 150 mg/kg daily) in specialist care.
• Cardiac care: diuretics and, where compatible with goals, surgery for repairable defects.
• Symptom control and comfort: morphine 0.05 to 0.1 mg/kg orally every 4 hours for distress, with palliative care.
• Hearing and vision assessment in survivors.
• Family support and counselling: recurrence risk is low (about 1%) for full trisomy, higher for parental translocation carriers. Bereavement support is offered.

Special groups.

• Mosaic or partial trisomy 13: outlook may be better and care follows the child's development.
• Prenatal diagnosis: counselling on options includes planned perinatal palliative care.

Monitoring. Review feeding, breathing, seizures and development at each visit, with echocardiography and other imaging as clinically indicated.

Referral and escalation. Refer to clinical genetics, neonatology and palliative care. Urgent for apnoea, cyanosis, seizures or feeding failure.