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 2 nd most common autosomal aberration 2 nd 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. , Palau et al. , Smith et al. ) PATHOGENESIS: 1. Genetics 1.
Trisomy 18 90% of cases due to meiotic nondisjunction less than 1% recurrence rate 2. Mosaicist 10% of cases due to post zygotic (post fertilization) 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 bi frontal diameter short palpebral 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 rocker bottom feet or equino varus short dorsiflexed big toes fixed flexion deformity of the fingers (overlapping of the 2 nd and 5 th fingers over the 3 rd and 4 th fingers) simple arch pattern of the fingers and toes hypoplasia of fingernails single crease of 5 th finger or all fingers (absence of interphalangeal flexion creases) simian crease 2. Organ Malformations 1. Central Nervous System severe mental retardation hypotonic -> hypertonic 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, hetero topic pancreas, mal rotation, Meckel’s, tracheoesophageal fistula 5. Genitourinary cryptorchidism congenital defects: double ureter, ectopic kidney, horseshoe kidney, hydro nephrosis, 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.