trisomy 18

Trisomy 18 arises from nondisjunction during meiosis (most commonly maternal meiosis I), resulting in three copies of chromosome 18 instead of two. Like trisomy 21, incidence increases with advanced maternal age. Unlike trisomy 21, most cases (>90%) are due to full trisomy from meiotic nondisjunction, though mosaicism and translocations can occur less commonly.

Clinical features are extensive and reflect widespread congenital malformations: intrauterine growth restriction (IUGR), low birth weight, prominent occiput, micrognathia (small jaw), low-set malformed ears, short sternum, clenched hands with overlapping index finger over third finger (classic finding), rocker-bottom feet, and congenital heart defects (VSD, ASD, PDA are most common). Renal anomalies (horseshoe kidney), omphalocele, and myelomeningocele may also be present.

Prognosis is poor—median survival is less than 2 weeks, with only about 5-10% surviving beyond the first year, often with severe intellectual disability and multiple comorbidities. Death is typically due to cardiac or respiratory failure, or apnea.

Diagnosis can be suspected prenatally via abnormal quad screen (decreased AFP, decreased hCG, decreased estriol, and normal to slightly increased inhibin A—differentiating it from trisomy 21 where inhibin A is elevated), ultrasound findings of characteristic anomalies, and confirmed via karyotype or chromosomal microarray. Cell-free fetal DNA screening has improved noninvasive detection.

Key USMLE associations: remember the mnemonic "3" for trisomy 18 - clenched fists with 3rd and 4th fingers overlapping, and rule of 3s for major features (3 body areas affected: craniofacial, cardiac, limb). Differentiate from trisomy 13 (Patau syndrome - cleft lip/palate, polydactyly, holoprosencephaly) and trisomy 21 (Down syndrome - more compatible with life, different quad screen pattern).