A 3-year-old boy is referred for stiff, toe-walking gait since he started walking at 18 months. He cannot run well and has difficulty climbing stairs. On examination, he has calf pseudohypertrophy, Gowers' sign, and proximal muscle weakness. CK is 25,000 IU/L. His maternal uncle had a similar condition and died at age 19. Which genetic mechanism explains why maternal uncle is affected?

• A The gene is autosomal recessive; the uncle shared both mutant alleles with the proband
• B The gene is X-linked recessive; males with one mutant X allele are affected, females are carriers ✓
• C The condition is autosomal dominant with variable expressivity
• D The uncle had de novo mutation; each case requires fresh mutation

Explanation

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (Xp21.1) and follows X-linked recessive inheritance. Males (XY) with one mutant X allele have no normal allele to compensate and are affected. Females (XX) with one mutant allele are carriers (usually asymptomatic, though some have mild features). A maternal uncle of a boy with DMD would have received his X chromosome from the same maternal lineage, explaining familial involvement. Autosomal recessive inheritance would not explain the selective male pattern across generations.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.