Edwards' Syndrome

Synonyms: Trisomy 18, Trisomy E syndrome

Edwards' syndrome is trisomy 18, with an extra chromosome 18 instead of the usual pair. It is a severe disorder that can affect all organs in the body. Mosaics can occur in about 5% of cases in which some cells are normal with 46 chromosomes and others have the extra chromosome. Partial trisomy 18 can (rarely) occur if a segment of chromosome 18 is present in triplicate, usually due to a balanced translocation carried by one parent.¹ Infants with mosaic and partial trisomy variations tend to be less severely affected.

• Trisomy 18 is the second most common autosomal trisomy among liveborn children after trisomy 21.¹
• Incidence is 1 in 6000 live births (taking into account prenatal diagnosis and termination of pregnancy).²
• In liveborn infants, it is more likely that the affected infant is female rather than male. This is thought to be due to the fact that male fetuses with trisomy 18 are more likely to be lost due to miscarriage or stillbirth.³

• A personal or close family history of giving birth to an affected child increases the risk.
• Risk rises with rising maternal age.

Most embryos or fetuses with trisomy 18 die (up to 95%).¹

In the prenatal period there may be:¹

• Polyhydramnios (possibly due to defective sucking and swallowing reflexes)
• Oligohydramnios (due to renal defects)
• Small placenta
• Single umbilical artery
• Intrauterine growth retardation
• Weak fetal activity
• Fetal distress

Features that may be noted after birth include:^1,2

• Low birth weight
• Craniofacial abnormalities:
  • Low set and malformed ears
  • Micrognathia (small jaw)
  • Prominent occiput
  • Small facial features: e.g. microphthalmia, microstomia
  • Microcephaly
  • Cleft lip and palate and/or narrow palate
  • Coloboma of iris
• Skeletal abnormalities:
  • Typical hand posture: clenched hands with index finger overriding middle finger and fifth finger overriding fourth finger
  • Thumb aplasia
  • Radial hypoplasia or aplasia
  • Pectus carinatum (short sternum)
  • Hypoplastic nails
  • Short, dorsiflexed hallux
  • Prominent calcaneus (rocker bottom feet)
• Congenital heart defects: > 90% have these, e.g. atrial septal defect, ventricular septal defect, patent ductus arteriosus, coarctation of aorta
• Gastrointestinal abnormalities: e.g. omphalocele, oesophageal atresia ± tracheo-oesophageal fistula, umbilical or inguinal hernia, diastasis recti, imperforate anus, pyloric stenosis
• Urogenital abnormalities: e.g. gonadal dysgenesis, cryptorchidism, prominent clitoris, horseshoe kidney, hydronephrosis, cystic kidneys, renal agenesis
• Neurological problems: anencephaly, hydrocephaly and other brain malformations, severe learning disability, neonatal hypotonia followed by hypertonia, seizures and jitters
• Pulmonary hypoplasia

• Edwards' syndrome and Patau's syndrome can have similar features and be difficult to differentiate.
• Pena-Shokeir syndrome is also known as pseudo-trisomy 18.²

• Cytogenetic studies and chromosome analysis will confirm the diagnosis.
• Organ systems will need specific investigation depending on the abnormality, e.g. echocardiography for cardiac abnormalities, skeletal radiography etc.
• Treatment of a liveborn infant is generally supportive but life sustaining measures are not always carried out. Considerable thought and discussion is recommended before undertaking measures such as surgical correction of abnormalities. Nasogastric or gastrostomy feeding is feasible but it is questionable if this is prolonging life or prolonging death.
• Parents will need a great deal of support and counselling. Support organisations may be useful (see below).
• If Edwards syndrome is due to an unbalanced translocation, both parents should undergo chromosomal analysis. It may be that the translocation in the infant occurred de novo but a balanced translocation may be found in one of the parents. This has significance for future pregnancies. Other family members may also be affected.²
• Screening and/or prenatal diagnosis should be offered for future pregnancies. For full trisomy 18, the risk of recurrence in a future pregnancy is less than 1%.¹ Risk may be higher if a parent carries a balanced translocation. Referral should be made to a geneticist as appropriate.

• Median life expectancy is 4 days. However, about 5 to 10% survive beyond one year, so the mean age at death is 48 days.²
• Useful statistics include:
  • Newborns have a 40% chance of surviving to age 1 month.
  • Infants have a 5% chance of surviving to age 1 year.
  • Children have a 1% chance of surviving to age 10 years.¹
• Those who survive have an increased risk of Wilms tumour and hepatoblastoma.²
• Death is usually due to severe cardiac, renal or central nervous system malformation, feeding difficulties or sepsis.¹

• Studies have looked at using human chorionic gonadotrophin (HCG), unconjugated oestriol (uE3), pregnancy-associated plasma protein A (PAPP-A) or combinations of these to detect Edwards' syndrome prenatally.
• Serum screening that is currently carried out for Down's syndrome may help to identify not only fetuses at risk of Down's syndrome but also those at risk of trisomy 13 and 18.
• A recent study looked at screening for trisomy 18 by using maternal age, fetal nuchal translucency, free β-human chorionic gonadotrophin and pregnancy-associated plasma protein-A, alongside screening for trisomy 21. More than 95% of trisomy 18 fetuses were detected.⁴
• Another study concluded that the addition of a trisomy 18-specific risk algorithm in the second trimester achieved high detection rates for aneuploidies other than Down syndrome. In this study, all patients had a nuchal scan in the first trimester, and those without cystic hygroma had a combined test (nuchal translucency, PAPP-A, free β-human chorionic gonadotrophin) and returned at 15-18 weeks for a quadruple screen using serum alpha-fetoprotein, total HCG, uE3 and inhibin-A.⁵
• Ultrasound: typical structural abnormalities may be detected on prenatal ultrasound and may raise the suspicion of Edwards' syndrome. Examples include persistent abnormal hand/finger position, choroid plexus cysts, cardiac defects, two-vessel umbilical cord.^1,6,7 A second trimester anatomical screening by ultrasound appears to be a good method of detection.⁸

• Amniocentesis or chorionic villus sampling is needed to make a definitive prenatal diagnosis.
• Cytogenetic study of fetal blood may also be carried out.

Trisomy 18 was described by Edwards et al in April 1960⁹ and by Smith et al in September 1960.¹⁰ It was John Edwards who gained the eponym.