What are the different types of myotonias?

Types of Myotonias

Myotonias are a heterogeneous group of disorders characterized by delayed muscle relaxation after contraction, with distinct genetic causes and clinical presentations that significantly impact morbidity, mortality, and quality of life.

Dystrophic Myotonias

Myotonic Dystrophy Type 1 (DM1)

• Also known as Steinert disease, DM1 is caused by expansion of an unstable CTG trinucleotide repeat in the 3′ untranslated region of the DMPK gene 1
• Inheritance is autosomal dominant with nearly complete penetrance but variable expressivity 1
• Normal alleles have 5-34 repeats, variable alleles have 35-49 repeats, and fully-variable (pathogenic) alleles have ≥50 repeats 1
• Clinical features include progressive facial, neck, and distal limb muscle weakness, myotonia, cataracts, neuropsychiatric deficits, and endocrine abnormalities 1
• Cardiac manifestations occur in approximately 80% of patients, including conduction defects and tachyarrhythmias, which are major causes of mortality 1
• Shows genetic anticipation, with successive generations showing earlier onset and more severe manifestations 1
• Congenital form presents with developmental delay, respiratory distress, and hypotonia 1

Myotonic Dystrophy Type 2 (DM2)

• Also known as proximal myotonic myopathy (PROMM) or Ricker disease 1
• Caused by expansion of a CCTG repeat in intron 1 of the CNBP gene 1
• Characterized by myotonia and muscle wasting, but with more variable clinical manifestations and later age of onset (20-70 years) than DM1 1
• Generally has a more favorable clinical course and life expectancy compared to DM1 1
• No genetic anticipation and no congenital form 1
• Cardiac problems are less frequent (10-20%) and typically less severe than in DM1 1

Non-Dystrophic Myotonias

Myotonia Congenita

• Caused by mutations in CLCN1, the gene coding for the main skeletal muscle chloride channel ClC-1 2, 3
• Results from reduced sarcolemmal chloride conductance 2
• Can be inherited as either autosomal dominant (Thomsen disease) or autosomal recessive (Becker disease) 2, 4
• Characterized by muscle stiffness that improves with repeated activity (warm-up phenomenon) 5, 3
• Symptoms include delayed muscle relaxation after voluntary contraction, leading to stiffness, pain, fatigue, and weakness 3
• Generally does not involve cardiac complications 1

Sodium Channel Myotonias

• Caused by gain-of-function mutations in the SCN4A gene encoding the voltage-gated sodium channel 3, 4
• Clinical variants include:
  • Paramyotonia congenita - characterized by cold-induced myotonia and paradoxical myotonia (worsening with repeated activity) 5, 4
  • Potassium-aggravated myotonia - exacerbated by potassium intake 4
  • Sodium channel myotonia - with variable temperature sensitivity 4
• Some mutations show marked temperature dependence in their effects 4
• Diagnosis confirmed by genetic testing and supported by electrophysiological findings 3

Clinical Evaluation and Diagnosis

• Diagnosis is based on history, examination findings, presence of electrical myotonia on electromyography, and genetic confirmation 3
• Electromyography shows myopathic changes with polyphasic motor unit action potentials of short duration and low amplitude 1
• Muscle biopsy can help distinguish inflammatory from non-inflammatory myopathies 1
• Magnetic resonance imaging is increasingly used to confirm myositis 1

Treatment Approaches

• Sodium channel blockers (such as mexiletine) are typically first-line treatment for symptomatic non-dystrophic myotonias 3
• Other medications that may reduce myotonia include tricyclic antidepressants (imipramine, clomipramine), benzodiazepines, calcium-antagonists, taurine, and prednisone 6
• Limited evidence suggests that imipramine and taurine may have beneficial effects in myotonic dystrophy 6
• Patients should be educated about potential anesthetic complications 3
• For dystrophic myotonias with cardiac involvement, cardiac monitoring and management are essential to reduce mortality 1

Important Considerations

• Cardiac screening is recommended for patients with myotonic dystrophy before anesthesia or sedation due to high risk of cardiac complications 1
• Neurologists managing patients with myotonic disorders should collaborate with cardiologists, especially for DM1 patients who have high cardiac risk 1
• Some patients with non-dystrophic myotonias may develop myopathy over time, but the frequency and severity remain undetermined 4
• The pathophysiological link between ion channel dysfunction and muscle degeneration is still unknown 4