Clinical Phenotype
Myotonic dystrophy type 1 (DM1): multisystem disease with myotonia, distal > proximal weakness, cardiac conduction defects, cataracts, endocrine dysfunction (diabetes, hypogonadism), and cognitive involvement. Congenital DM1 is the most severe form.
Molecular Mechanism
CTG trinucleotide repeat expansion in the 3' UTR of DMPK. Mutant RNA containing expanded CUG repeats sequesters MBNL1 splicing factor, causing widespread mis-splicing across many tissues. Genetic anticipation: repeat length increases with each generation, correlating with severity.
Clinical Hallmarks & Key Evidence
Genetic anticipation is the rule: repeat lengths >50 cause adult-onset DM1; >1000 cause congenital DM1 — the most severe form, often transmitted maternally.
Harper PS. Myotonic Dystrophy. 3rd ed. 2001.
Myotonia (impaired relaxation after contraction) can be elicited clinically by percussion of the thenar eminence or wrist extensors.
Thornton CA. Neurol Clin. 2014;32(3):705-719.
Cardiac arrhythmia is the second leading cause of death in DM1; annual ECG and Holter monitoring are standard of care.
Wahbi K et al. Circulation. 2012;125(11):1342-50.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.