- Clinical science
Myotonic syndromes
Summary
Myotonic syndromes are a heterogenous group of inherited disorders with similar pathological mechanisms. 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
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Myotonic dystrophies
- One of the most common forms of adult-onset muscular dystrophy
- Myotonic dystrophy type I: congenital, juvenile, or adult onset
- Myotonic dystrophy type II: usually adult onset
References:[1][2]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
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Myotonic dystrophies
- Autosomal dominant condition
- Type 1: CTG trinucleotide repeat expansion of the DMPK gene
- Type 2: CCTG tetranucleotide repeat expansion of the ZNF9 gene (CNBP gene)
Clinical features
(DM1, Curschmann-Steinert disease) | (DM2, proximal myotonic myopathy) |
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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.
References:[1]
Diagnostics
- Electromyography (EMG): identifies 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 ↓/↔︎ testosterone
- ECG: to exclude cardiac arrhythmias and other abnormalities
- MRI: signs of global atrophy
References:[3][1]
Differential diagnoses
Myotonic dystrophies | Duchenne muscular dystrophy | Becker muscular dystrophy | |||||
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Type 1 (DM1; Curschmann-Steinert disease) | Type 2 (DM2; Proximal Myotonic Myopathy, PROMM) | ||||||
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References:[4][1]
The differential diagnoses listed here are not exhaustive.
Treatment
- 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
References:[1][2]
Prognosis
- The course of DM1 is chronic progressive. Cardiac complications reduce life expectancy.
- DM2 has a milder disease course.