Myotonic Dystrophy and Non-Dystrophic Myotonias

Genetic Characteristics and Clinical Presentations

Myotonic Dystrophy Type 1 (DM1) is caused by expansion of an unstable CTG trinucleotide repeat in the 3′ untranslated region of the DMPK gene, with normal alleles having 5-34 repeats, variable alleles having 35-49 repeats, and fully-variable (pathogenic) alleles having ≥50 repeats, according to the American College of Medical Genetics and Genomics 1, 2
Inheritance of DM1 is autosomal dominant with nearly complete penetrance but variable expressivity, as stated by the National Society of Genetic Counselors 2
Myotonic Dystrophy Type 2 (DM2) is caused by expansion of a CCTG repeat in intron 1 of the CNBP gene, characterized by myotonia and muscle wasting, but with more variable clinical manifestations and later age of onset (20-70 years) than DM1, as reported by the American Heart Association 1, 2

Cardiac manifestations occur in approximately 80% of patients with DM1, including conduction defects and tachyarrhythmias, which are major causes of mortality, according to the American College of Cardiology 1, 3
Cardiac problems are less frequent (10-20%) and typically less severe in DM2 than in DM1, as stated by the Heart Rhythm Society 1, 3
For dystrophic myotonias with cardiac involvement, cardiac monitoring and management are essential to reduce mortality, as recommended by the American Heart Association 1, 3

Electromyography shows myopathic changes with polyphasic motor unit action potentials of short duration and low amplitude, which can aid in diagnosis, as reported by the American Association of Neuromuscular and Electrodiagnostic Medicine 4
Muscle biopsy can help distinguish inflammatory from non-inflammatory myopathies, as stated by the College of American Pathologists 4

Cardiac screening is recommended for patients with myotonic dystrophy before anesthesia or sedation due to high risk of cardiac complications, as advised by the American Society of Anesthesiologists 5
Neurologists managing patients with myotonic disorders should collaborate with cardiologists, especially for DM1 patients who have high cardiac risk, as recommended by the American Academy of Neurology 5

Myotonic Dystrophy Type 1 is caused by an expansion of a CTG trinucleotide repeat in the 3′ untranslated region of the DMPK gene on chromosome 19; normal alleles contain 5‑34 repeats, variable alleles 35‑49 repeats, and pathogenic alleles have ≥ 50 repeats. 6

The disorder follows an autosomal dominant inheritance pattern with nearly complete penetrance but highly variable expressivity; it demonstrates anticipation, meaning disease severity and earlier onset increase in successive generations. 6

Congenital form (typically > 1000 CTG repeats) presents in infancy with severe hypotonia, respiratory distress, developmental delay, and a high rate of early mortality. 6
Mild adult form (approximately 50‑100 CTG repeats) may manifest only subtle myotonia and can be accompanied by additional features such as cataracts or a positive family history. 6

Genetic testing with CTG repeat analysis is the definitive diagnostic test for Myotonic Dystrophy Type 1; for non‑dystrophic myotonias, clinical evaluation combined with targeted genetic testing for channel mutations confirms the diagnosis. 6

In patients with Myotonic Dystrophy Type 1 who require permanent pacing, implantation of an implantable cardioverter‑defibrillator (ICD) is recommended over a pacemaker alone to reduce the risk of sudden cardiac arrest due to ventricular tachycardia. 7