Essay, Research Paper: TRIDOMY 18

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