A newborn girl is profoundly hypotonic with bilateral talipes equinovarus, respiratory insufficiency requiring ventilation, and a triangular face. Her mother has grip myotonia, ptosis, frontal balding, and cataracts, and had been diagnosed with myotonic dystrophy type 1. The severe congenital presentation in the infant is best explained by:

• A Paternal transmission of a massively expanded CTG repeat
• B Homozygosity for a DMPK missense mutation
• C Maternal transmission of a premutation allele
• D Maternal transmission of a massively expanded CTG repeat ✓

Explanation

Myotonic dystrophy type 1 results from CTG repeat expansion in DMPK on chromosome 19. Congenital myotonic dystrophy, with neonatal hypotonia, respiratory failure, and arthrogryposis, occurs almost exclusively when the severely expanded allele is transmitted by an affected mother, since expansions enlarge during oogenesis. Paternal transmission expands as well but rarely to the congenital range. Premutations are a fragile X concept, and myotonic dystrophy is a dominant gain-of-function RNA toxicity disorder, not a recessive missense 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.