A newborn girl born to a mother with adult-onset myotonic dystrophy presents with generalized hypotonia, facial diplegia, feeding difficulty requiring tube feeds, and bilateral talipes equinovarus. The molecular basis for this severe congenital phenotype is:

• A Paternal transmission of a premutation allele that expands on spermatogenesis
• B Maternal transmission of a markedly expanded CTG repeat causing extreme anticipation ✓
• C Uniparental disomy of chromosome 19 silencing the DMPK gene
• D Anticipation driven exclusively by paternal transmission of the expanded allele

Explanation

Myotonic dystrophy type 1 results from CTG repeat expansion in the DMPK gene on chromosome 19. Anticipation is strong in both sexes, but congenital myotonic dystrophy with neonatal hypotonia and respiratory weakness arises almost exclusively through maternal transmission, when the mother passes on an enormously expanded repeat. Paternal transmission classically drives anticipation in Huntington disease, not here, and DMPK is not imprinted.

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.