Edwards Syndrome (Trisomy 18)

Introduction and Epidemiology

Second most common viable autosomal trisomy compatible with live birth, following Trisomy 21.
Incidence is approximately 1 in 5000 to 1 in 6000 live births.
Risk increases with advancing maternal age.
Highly lethal in utero, with 85-95% of affected conceptuses resulting in spontaneous abortion or fetal demise.
Female-to-male ratio is approximately 3:1 among live-born infants due to higher in utero mortality of affected male fetuses.

Caused by an extra copy of genetic material from chromosome 18, leading to gene dosage imbalance that alters embryogenesis.
Full Trisomy 18 (90-95%): Caused by meiotic nondisjunction, primarily during maternal meiosis II, resulting in 47 chromosomes in all somatic cells.
Mosaic Trisomy 18 (<5%): Results from post-zygotic mitotic nondisjunction, presenting with a highly variable phenotype depending on the tissue distribution of trisomic cells.
Partial Trisomy 18 (rare): Caused by an unbalanced translocation or chromosomal structural rearrangement, often involving duplication of the 18q segment.

System	Clinical Features
Craniofacial	Microcephaly, prominent occiput (dolichocephaly), micrognathia, retrognathia, low-set malformed “fawn-like” ears, short palpebral fissures, cleft lip and palate.
Musculoskeletal	Clenched hands (index finger overlapping the third digit, fifth digit overlapping the fourth), rocker-bottom feet with prominent calcanei, hypoplastic nails, short sternum, severe hypertonia, limited hip abduction, shield-shaped chest.
Cardiovascular	Congenital heart disease present in >90% of cases (VSD, ASD, PDA, polyvalvular dysplasia, Tetralogy of Fallot).
Neurological	Profound intellectual disability, severe global developmental delay, central apnea, neonatal seizures, structural anomalies like agenesis of the corpus callosum.
Gastrointestinal	Omphalocele, esophageal atresia, tracheoesophageal fistula, Meckel diverticulum, biliary atresia.
Genitourinary	Horseshoe kidney, ectopic kidneys, cryptorchidism, prominent clitoris.

First-trimester combined screen: Reveals low free beta-hCG, low PAPP-A, and increased nuchal translucency.
Second-trimester quadruple screen: Reveals low AFP, low unconjugated estriol, and low beta-hCG.
Non-Invasive Prenatal Testing (NIPT): Provides high sensitivity (>97%) and specificity using cell-free fetal DNA.
Fetal ultrasonography: Identifies severe intrauterine growth restriction (IUGR), choroid plexus cysts, strawberry-shaped calvarium, single umbilical artery, and major structural anomalies.

Karyotyping: Gold standard confirming 47,XX,+18 or 47,XY,+18.
Fluorescence In Situ Hybridization (FISH): Enables rapid preliminary detection within 24-48 hours.
Chromosomal Microarray (CMA): Useful for detecting extra copies and clarifying partial trisomies or complex rearrangements.
Postnatal baseline screening: Urgent echocardiography, cranial ultrasonography, renal/abdominal ultrasonography, and hearing screening.

Management involves individualized care and shared decision-making with parents, ranging from palliative comfort care to full invasive intensive care.
Interventions may include non-invasive positive pressure ventilation for central apnea, gastrostomy tube placement for feeding, and aggressive seizure control.
Palliative or corrective cardiac surgeries are increasingly offered to selected surviving infants.
Oncology screening: Long-term survivors have an increased risk of Wilms tumor and hepatoblastoma, requiring abdominal ultrasound and AFP screening every 3 months until age 7.
Prognosis remains exceptionally poor; median survival is 3 to 15 days.
Approximately 40% survive to 1 month, and only 5-10% survive to 1 year.
Recurrence risk for full Trisomy 18 is 1% or the maternal age-related risk; parents of children with unbalanced translocations require mandatory karyotyping.