Edwards syndrome

Edwards syndrome, also known as trisomy 18, along with Down syndrome (trisomy 21) and Patau syndrome (trisomy 13), make up the only three autosomal trisomies to be compatible with extrauterine life in non-mosaic forms, albeit in the case of Edward syndrome only for a week or so. 

Epidemiology

After Down syndrome, it is the second most common autosomal trisomy and the overall incidence is estimated to be at ~1:3000-8000. There is an increase in incidence with increasing maternal age.

Clinical presentation

Trisomy 18 fetuses can have multiple anomalies in multiple systems. Over 130 features have been reported. Out of the three main trisomies, this trisomy has the highest incidence of major structural anomalies. A mnemonic for common associations can be found here. Features include:

• congenital heart disease: 90-95%

  • atrial septal defect (ASD)

  • ventricular septal defect (VSD)

  • patent ductus arteriosus (PDA)

  • dextrocardia

• central nervous system or spinal abnormalities: 70%

  • choroid plexus cysts (especially if cysts are large and bilateral ⁶): found in 25-43% with trisomy 18 

  • agenesis of the corpus callosum: <10%

  • Dandy-Walker continuum

  • mega cisterna magna ⁶

  • intellectual disability

  • neural tube defects: ~20% ⁷

    • myelomeningocele

    • spina bifida

• intrauterine growth restriction (IUGR): 60-90% (tends to occur from early in gestation)

• facial/calvarial abnormalities

  • micrognathia

  • dolichocephaly: strawberry skull: as a result of frontal lobe hypoplasia

  • low set ears

  • hypertelorism

  • cleft lip +/- palate

• cystic hygroma: ~20%

• skeletal abnormalities

  • hand anomalies

    • clenched hands with an overlap of 2^nd and 3^rd digits: 80%

    • radial ray anomalies

    • absent thumb

  • feet anomalies

    • rocker bottom feet: a typical feature

    • clubfeet

  • prominent occiput

  • short neck

  • 11 pairs of ribs ¹⁰

• umbilical cord

  • single umbilical artery: 80%

  • umbilical cord cysts

  • umbilical cord pseudocysts

• gastrointestinal: thoracic anomalies

  • bowel containing omphalocele: 20-25%

  • congenital diaphragmatic hernia: ~10%

• renal anomalies

  • antenatal hydronephrosis

  • urethral duplication

  • horseshoe kidney: 20% ³

Pathology

Markers

The following serological markers (often termed a triple screen) are generally lower than expected for that of pregnancy:

• MSAFP: maternal serum alpha fetoprotein

• oestriol

• beta human chorionic gonadotropin (bHCG)

Treatment and prognosis

The syndrome carries an extremely poor prognosis with a mean infant survival of 48 days ⁴. The risk of recurrence for a future pregnancy is ~1% greater than that adjusted for maternal age ⁷.

History and etymology 

The syndrome was first described by John Hilton Edwards (1928–2007), a British medical geneticist ⁸. Historically it was also called E-trisomy or trisomy E ^9,10.

Differential diagnosis

• Pena-Shokeir syndrome (pseudotrisomy 18): an autosomal recessive condition that may share some overlap in its clinical features with trisomy 18