Preparatory Mindset

Chromosome disorders are surprisingly common (1/150 live births). Most arise from meiotic nondisjunction. Only a few autosomal trisomies are viable. Sex chromosome aneuploidies are much better tolerated. Know the classic syndromes and their karyotypes.

Core Concepts

• Nondisjunction: Failure of chromosomes to separate in meiosis I or II → gamete with extra/missing chromosome


• Trisomy 21 (Down syndrome): 47,XX/XY,+21 — intellectual disability, flat facies, single palmar crease, CHD, ↑ risk with maternal age


• Trisomy 18 (Edwards syndrome): 47,XX/XY,+18 — severe ID, rocker-bottom feet, clenched hands, rarely survive first year


• Trisomy 13 (Patau syndrome): 47,XX/XY,+13 — cleft lip/palate, polydactyly, holoprosencephaly, severe brain malformations


• Turner syndrome (45,X) : Webbed neck, low hairline, widely spaced nipples, short stature, lymphedema — ONLY viable monosomy


• Klinefelter syndrome (47,XXY) : Tall, hypogonadism, gynecomastia, infertility, mild learning difficulties


• 47,XYY: Tall, normal intelligence, increased risk of learning/behavioral issues


• 47,XXX (Triple X) : Tall, normal phenotype, may have learning difficulties


• Robertsonian translocation: Fusion of two acrocentric chromosomes at centromere → carrier has 45 but is normal


• Unbalanced translocation: Net gain/loss of chromosome material → abnormal phenotype


• Mosaicism: Two+ cell lines with different karyotypes in same individual (usually milder phenotype)

High-Yield Points

• Most common meiotic error = nondisjunction (↑ with maternal age)


• Viable autosomal trisomies: only 13, 18, 21 (and most abort spontaneously)


• Turner (45,X) = only viable monosomy


• Robertsonian translocation carriers: 45 chromosomes, phenotypically normal

Topic Summary

Chromosome aneuploidy results from meiotic nondisjunction. Only trisomy 13, 18, and 21 are viable. Sex chromosome aneuploidies are better tolerated. Structural abnormalities include translocations, deletions, and inversions.