A 34-year-old man whose father developed chorea and cognitive decline at age 40 now develops similar symptoms at age 26, with MRI showing caudate head atrophy. His asymptomatic daughter asks about the risk to her own children. The key genetic principle governing hereditary transmission in this family is:

• A Expansion occurs only through maternal transmission, so her sons are protected
• B Further expansion is unlikely once the repeat exceeds 40 copies
• C Expanded alleles tend to enlarge further during spermatogenesis, driving anticipation ✓
• D His daughter will develop disease only if her mother also carries the mutation

Explanation

Huntington disease is caused by CAG repeat expansion in the HTT gene on chromosome 4. The expanded allele is unstable during spermatogenesis, so paternal transmission commonly produces larger repeats in the next generation, causing anticipation and earlier onset; very large expansions produce juvenile Huntington disease. This contrasts with myotonic dystrophy, where congenital disease follows maternal transmission. It is autosomal dominant, so the mother's genotype is irrelevant.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.