Nelson Textbook of Pediatrics 22nd Edition — Myotonic dystrophy type 1 (DM1): CTG trinucleotide repeat expansion in DMPK (19q13). Anticipation, distal weakness, myotonia, cataracts, cardiac conduction defects, frontal balding, endocrine abnormalities. Congenital form (maternal transmission) → severe hypotonia, respiratory failure, arthrogryposis.
🌐 paeds.online — Pakistan's Pediatric Platform| Feature | Classic/Adult-Onset DM1 | Congenital DM1 |
|---|---|---|
| Onset | Adolescence to adulthood | Birth (severe) |
| Transmitting parent | Either parent | Mother (94% of cases) |
| CTG repeat size | 50-1,000 | >1,000 (large expansions) |
| Muscle weakness | Distal > proximal, facial | Severe generalized hypotonia |
| Myotonia | Present (after age 5) | Absent in neonatal period |
| Facial appearance | Myopathic facies, temporal wasting, tented upper lip | Tented upper lip, open mouth, dolichocephaly |
| Arthrogryposis | No | Common (contractures, clubfeet) |
| Respiratory | Progressive weakness | Respiratory failure at birth, diaphragmatic weakness |
| Cardiac | Conduction defects (PR, QRS), heart block, atrial fibrillation | Less common in infancy but develops later |
| Prognosis | Slow progression, reduced lifespan | High neonatal mortality; survivors have intellectual disability and weakness |
CTG repeat expansion in DMPK gene (19q13.3). Normal: 5-37 repeats; affected: >50 repeats; congenital: often >1,000 repeats. Anticipation: increasing severity and earlier onset in successive generations due to repeat expansion during maternal transmission.
RNA toxicity: Mutant DMPK mRNA accumulates in nuclei, sequestering splicing regulators (MBNL1) → aberrant splicing of multiple genes → multisystem disease (muscle, heart, brain, endocrine, eyes).
Myotonia treatment: Mexiletine (first-line), phenytoin, carbamazepine. Avoid drugs that prolong QT.