A mother with mild myotonia and early cataracts delivers a baby with generalized hypotonia, facial diplegia, and respiratory insufficiency requiring ventilatory support. Molecular analysis of the DMPK gene shows marked expansion of a CTG repeat. The severe congenital form in this infant is best explained by:
- A Paternal transmission of a large expansion, since expansions enlarge preferentially in spermatogenesis
- B Mitochondrial heteroplasmy inherited from the mother
- C Maternal transmission of a large expansion, since expansions enlarge markedly in oogenesis ✓
- D Uniparental disomy of chromosome 19 affecting the maternal allele
Correct answer: C. Maternal transmission of a large expansion, since expansions enlarge markedly in oogenesis
Explanation
Myotonic dystrophy type 1 results from CTG expansion in DMPK on chromosome 19. In this disorder, anticipation is strongly tied to maternal transmission: expansions can enlarge dramatically during oogenesis, and virtually all congenital myotonic dystrophy cases are inherited from affected mothers. This contrasts with Huntington disease, where large expansions arise through paternal transmission. Mitochondrial heteroplasmy applies to disorders such as MELAS, not to this autosomal dominant trinucleotide repeat condition.
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.