A neonate presents with low birth weight, overlapping fingers with clenched fists, rocker-bottom feet, cardiac defects, and severe intellectual disability. Chromosome analysis reveals trisomy 18. Which molecular mechanism underlying trisomy 18 (Edwards syndrome) differentiates it from trisomy 21 in terms of chromosomal origin?

• A Trisomy 18 arises predominantly from maternal meiosis II non-disjunction, while trisomy 21 predominantly involves maternal meiosis I non-disjunction; both show maternal age effect ✓
• B Trisomy 18 is almost always due to paternal meiotic non-disjunction in meiosis I, unlike trisomy 21 which is maternal
• C Trisomy 18 results exclusively from robertsonian translocation involving chromosome 18, unlike trisomy 21 which can be free trisomy or translocation
• D Trisomy 18 is caused by uniparental disomy (UPD) of chromosome 18, explaining its imprinting-dependent severity

Explanation

Both trisomy 18 and trisomy 21 demonstrate maternal age effect, reflecting age-dependent deterioration of the first and second meiotic spindle assembly checkpoints in oocytes. Trisomy 18 predominantly results from maternal meiosis II errors (failure of sister chromatid separation), while trisomy 21 more often involves maternal meiosis I errors (failure of homolog separation). Both share the same ultimate mechanism: non-disjunction in maternal meiosis. Trisomy 18 is not due to Robertsonian translocation (chromosomes 13, 14, 15, 21, and 22 are acrocentric and participate in Robertsonian translocations; chromosome 18 does not). UPD is not the primary mechanism.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.