Myotonic syndromes

Myotonic syndromes are a heterogeneous group of inherited disorders with similar pathological mechanisms. Myotonic syndromes are subdivided into dystrophic myotonic syndromes and nondystrophic myotonic syndromes. Nondystrophic myotonic syndromes are channelopathies and include Thomsen disease, Becker disease, and Eulenberg disease. The channelopathies are autosomal dominant or autosomal recessive conditions caused by defective ion channels in the skeletal muscle sarcolemma. All three diseases manifest with myotonia, muscle stiffness, and weakness. Thomsen disease and Becker disease are furthermore characterized by muscular hypertrophy. Myotonic dystrophies, the most prevalent myotonic syndromes, are one of the most common forms of adult-onset muscular dystrophy. Both types, myotonic dystrophy type I (Curschmann-Steinert disease) and myotonic dystrophy type II (proximal myotonic myopathy), are autosomal dominant conditions with CTG trinucleotide repeat and CCTG tetranucleotide repeat expansions respectively. Type I is a severe (often life-threatening) form of disease, while type II is usually mild. Both present with skeletal muscle weakness and myotonia, muscle pain, heart conduction defects, cataracts, testicular atrophy, and frontal balding. Electromyography may confirm myotonia that is not identified during clinical examination; however, genetic tests usually confirm the diagnosis. As no curative therapy exists, treatment is symptomatic. Except for DM1, patients with myotonic syndromes have a normal lifespan.

Epidemiology ^[1][2]

• One of the most common forms of adult-onset muscular dystrophy

Etiology

• Autosomal dominant conditions
• Type 1: CTG trinucleotide repeat expansion in the DMPK gene → changes in myotonin protein kinase expression
• Type 2: CCTG tetranucleotide repeat expansion of the ZNF9 gene (CNBP gene)

Clinical features ^[1]

Myotonic dystrophy type I is caused by a CTG nucleotide repeat expansion and results in Cataracts, Toupee (premature hair loss in men), and Gonadal atrophy.

Diagnostics ^[1][3]

• Electromyography: (EMG): allows for the identification of myotonia
• Genetic diagnostics: (confirmatory test) detection of trinucleotide repeat expansion mutation in leukocytes
• Biopsy: to distinguish between an inflammatory and a metabolic cause of the myopathy
• Other supportive tests
  • ↑ CK, IgG and IgM hypogammaglobulinemia, ↑ FSH and ↓/normal testosterone
  • ECG: to exclude cardiac arrhythmias and other abnormalities
  • MRI: signs of global atrophy

Electromyography (EMG) is used to measure the activity of muscles in response to neural stimulation. A needle electrode is inserted into a muscle, and the electrical activity measured in the resting muscle (tonic activity) and during movements (phasic muscle activity). An EMG can be used to detect dysfunction at the level of the neuromuscular junction, the muscle, or the corresponding nerve.

Treatment ^[1][2]

• Incurable
• Symptomatic treatment (e.g., analgesia, physiotherapy, walking aids, pacemaker, medical therapy for myotonia )
• Regular monitoring (i.e., of respiratory compromise, dysphagia)
• Genetic counseling and testing

Prognosis

• The course of DM1 is chronic progressive. Cardiac complications reduce life expectancy.
• DM2 has a milder disease course.

Epidemiology ^[4]

• Rare disorders (prevalence < 1:100,000)

Etiology and clinical features ^{[5] [4]}

Diagnostics

• Percussion myotonia: percussion of a muscle results in myotonia with delayed muscle relaxation (e.g., tapping the thenar eminence with a reflex hammer causes the thumb to abduct)
• EMG: repetitive discharges with oscillating frequency and amplitude (crescendo-decrescendo sound )
• Genetic testing: confirms the diagnosis

Treatment ^[5]

• Mild cases
  • Usually no treatment necessary
  • Avoid precipitating factors, e.g., strenuous exercise.
• Severe cases
  • Sodium channel blocker (e.g., mexiletine, carbamazepine, tocainide)
  • Acetazolamide

Prognosis

• Incurable
• Varying degree of life-long disability but no effect on life expectancy
• No symptom progression throughout the course of the disease

The differential diagnoses listed here are not exhaustive.

1. Thornton CA. Myotonic dystrophy. Neurol Clin. 2014; 32 (3): p.705-719. doi: 10.1016/j.ncl.2014.04.011 . | Open in Read by QxMD
2. Matthews E, Fialho D, Tan SV, et al. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain. 2009; 133 (1): p.9-22. doi: 10.1093/brain/awp294 . | Open in Read by QxMD
3. Myotonic syndromes. https://www.ncbi.nlm.nih.gov/pubmed/12351998. Updated: October 1, 2002. Accessed: April 2, 2017.
4. Trivedi JR, et al.. Nondystrophic Myotonia: Challenges and Future Directions. Experimental Neurology. 2013 .
5. Matthews E., et al.. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain. 2009 .