Edwards Syndrome

Edwards syndrome (trisomy 18) is a chromosomal disorder with multiple congenital anomalies, severe developmental disability and markedly reduced survival. It affects about 1 in 5000 live births, and most affected pregnancies end in loss before term.

Pathophysiology. Most cases are full trisomy 18 from maternal meiotic non-disjunction, with risk rising with maternal age. A minority have mosaic or partial trisomy, with milder disease.

Translocation cases are rare and carry a recurrence risk when a parent is a balanced carrier.

Survival to the first year is uncommon in full trisomy, while mosaic disease has longer survival. Management depends on the family's wishes, the child's condition and available care.

• Low birth weight, hypotonia and feeding difficulty
• Prominent occiput, narrow forehead, small mouth, micrognathia, low set malformed ears
• Clenched hands with overlapping index and fifth fingers
• Rocker bottom feet and short sternum
• Congenital heart disease: ventricular septal defect, atrial septal defect, patent ductus arteriosus, polyvalvular disease
• Central apnoea and respiratory failure
• Renal anomalies: horseshoe kidney, hydronephrosis
• Oesophageal atresia, omphalocele, diaphragmatic hernia
• Severe developmental delay, seizures
• Increased risk of Wilms tumour and hepatoblastoma

• Prenatal screening: raised risk on combined screening or cell free DNA testing, with ultrasound findings (clenched hands, cardiac defects, choroid plexus cysts, growth restriction).
• Prenatal diagnosis: amniocentesis or chorionic villus sampling with karyotype or microarray.
• Postnatal confirmation: rapid FISH or quantitative PCR within days, then karyotype to identify the type (full, mosaic or translocation).
• Echocardiography, renal and cranial ultrasound, and chest and abdominal imaging to define anomalies.
• Parental karyotype when a translocation is found.

Differential diagnosis.

• Patau syndrome (trisomy 13)
• Triploidy
• Smith-Lemli-Opitz syndrome
• Pena-Shokeir sequence and other foetal akinesia sequences
• Distal arthrogryposis
• Other causes of multiple congenital anomalies with growth restriction

• Individualised care planning: discuss prognosis honestly with parents, and decide with them between comfort focused care and active treatment, revisiting decisions as the child's condition changes. A multidisciplinary team including palliative care is involved from diagnosis.
• Respiratory support: oxygen, airway management, and ventilatory support where chosen. Treat central apnoea with caffeine citrate 20 mg/kg loading then 5 to 10 mg/kg daily when appropriate.
• Feeding: nasogastric tube feeding, then gastrostomy with or without anti-reflux procedure when feeding is prolonged. Treat reflux with omeprazole 0.7 to 1 mg/kg daily.
• Cardiac care: diuretics (furosemide 1 mg/kg once or twice daily) for heart failure, and discussion of surgical repair when it is in keeping with goals of care.
• Seizures: treatment with levetiracetam 10 mg/kg twice daily increasing to 30 mg/kg twice daily if needed.
• Tumour surveillance: abdominal ultrasound every 3 months to 8 years for Wilms tumour and hepatoblastoma, with alpha fetoprotein in infancy.
• Infection: treat chest and urinary infections promptly.
• Family support: bereavement support, siblings' support, and genetic counselling. Recurrence risk is about 1% after a full trisomy and higher with translocation.
• Pain and symptom control: morphine 0.05 to 0.1 mg/kg orally every 4 hours or comfort based sedation for distress, with palliative care input.

Special groups.

• Mosaic trisomy 18: outlook is more variable and intervention follows the child's development.
• Prenatal diagnosis: offer counselling on options, including continuing the pregnancy with planned perinatal palliative care.

Monitoring. Review growth, feeding, breathing and development at every visit. Echocardiography as indicated by cardiology, and abdominal ultrasound for tumour surveillance every 3 months to 8 years.

Referral and escalation. Refer to clinical genetics, neonatology, paediatric cardiology and palliative care. Urgent for apnoea, cyanosis, poor feeding with vomiting, or abdominal distension.