TRISOMY 18 SYNDROME

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:

1. Genetics

1. Trisomy 18

90% of cases

due to meiotic nondisjunction

less than 1% recurrence rate

2. Mosaicism

10% of cases

due to postzygotic (postfertilization) mitotic nondisjunction

leads to the partial clinical expression of Trisomy 18 with a longer survival

3. 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:

1. 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

2. 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:

1. Imaging Studies

to rule out organ malformations:

cardiovascular anomalies - Echo

gastrointestinal anomalies - Barium Swallow, Endoscope

genitourinary anomalies - Ultrasound

2. Karyotyping

MANAGEMENT:

1. Supportive

very poor prognosis with:

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