Trisomy 18

Introduction

Karyotype Trisomy 18 male

(Edwards Syndrome) An aneuploidy, first recognized as a specific clinical entity by the discovery of an extra chromosome 18 in babies with a particular pattern of malformation by three independent groups (Edwards et al., Patau et al., Smith et al.).

Pedbase Entry

Definition

A chromosomal disorder resulting in a syndrome characterized by specific (small) dysmorphic features and organ malformations.

Epidemiology

incidence: 1/8000 live births most die in embryonic or fetal life 2nd most common autosomal aberration 2nd most common multiple malformation syndrome age of onset: newborn risk factors: advanced maternal age F > M (4:1)

History

1960 first recognized as a specific clinical entity by the discovery of an extra chromosome 18 in babies with a particular pattern of malformation by three independent groups (Edwards et al., Patau et al., Smith et al.)

Pathogenesis - Genetics=

Trisomy 18

90% of cases due to meiotic nondisjunction less than 1% recurrence rate

Mosaicism

10% of cases due to postzygotic (postfertilization) mitotic nondisjunction leads to the partial clinical expression of Trisomy 18 with a longer survival

Translocations

very rare give rise to partial trisomy 18 syndromes short arm: causes non-specific clinical features with mild or no mental deficiency long arm: entire: clinically indistinguishable from trisomy 18 distal 1/3 -> : partial clinical picture of trisomy 18 with a longer survival and less profound mental retardation

Clinical Features

Dysmorphic Features

1. Facial

• microcephaly with prominent occiput
• narrow bifrontal diameter
• short palpabral fissures
• low-set malformed ears
• cleft lip +/- palate
• narrow palatal arch
• micrognathia

2. Skeletal

• neck - webbed
• chest - short sternum, widely spaced nipples
• hips - small pelvis, congenital dislocation of the hips, limited hip abduction
• extremities - phocomelia, rockerbottom feet or equinovarus, short dorsiflexed big toes, fixed flexion deformity of the fingers (overlapping of the 2nd and 5th fingers over the 3rd and 4th fingers), simple arch pattern of the fingers and toes, hypoplasia of fingernails, single crease of 5th finger or all fingers (absence of interphalangeal flexion creases), simian crease

Organ Malformations

1. Central Nervous System

• severe mental retardation
• hypotonia -> hypertonia
• neural tube defects
• poor suck and weak cry
• failure to thrive
• ocular anomalies

2. Respiratory

• apnea

3. Cardiovascular( >95%)

• major: VSD, ASD, PDA
• minor: transposition, ToF, coarctation, anomalous coronary artery, dextrocardia, aberrant subclavian artery, arteriosclerosis, PS, bicuspid aortic and/or pulmonic valves

4. Gastrointestinal

• inguinal, umbilical, and/or diaphragmatic hernia
• congenital defects: diastasis recti, heterotopic pancreas, malrotation, Meckel's, tracheoesophageal fistula

5. Genitourinary

• cryptorchidism
• congenital defects: double ureter, ectopic kidney, horseshoe kidney, hydronephrosis, polycystic kidney

Investigations

Imaging Studies

• to rule out organ malformations:
• cardiovascular anomalies - Echo
• gastrointestinal anomalies - Barium Swallow, Endoscope
• genitourinary anomalies - Ultrasound

Management

Supportive, very poor prognosis.

• 30% dying by 1 month of age
• 50% dying by 2 months of age
• 90% dying by 12 months of age

Genetic counselling, recurrence rate depends on genotype.

(modified from original 1999 Pedbase entry)