IllnessMyotonia congenita, differential diagnosis

NGS +

Non-dystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Myotonia congenita affects skeletal muscles beginning in childhood with bouts of sustained myotonia of any muscles, including of the face and tongue, but most often in the legs causing stiffness sometimes with warm-up effect. The two major types are designated Thomsen disease and Becker disease as distinguished by the severity of symptoms and patterns of inheritance. Becker disease usually appears later in childhood causing more severe stiffness. Becker disease patients often experience temporary attacks of muscle weakness, sometimes permanent over time. Mutations in the CLCN1 gene alter structure and/or function of chloride channels. Thomsen disease is transmitted in an autosomal dominant pattern, Becker disease is inherited in an autosomal recessive manner. The phenotypic manifestations of the pathogenic variants in the CLCN1 and SCN4A genes can be variable even within the same family; many autosomal dominant pathogenic variants can be associated with reduced penetrance. Both, the analytical sensitivity and specificity are close to 100%, the clinical sensitivity and specificity are dependent on variable factors such as age and/or family history.

Reference:

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1355/

• Alias: Non-dystrophic skeletal muscle disorder
• Alias: Thomsen + Becker disease
• Allelic: Cardiomyopathy, familial hypertrophic (CAV3)
• Allelic: Creatine phosphokinase, elevated serum (CAV3)
• Allelic: Long QT syndrome 9 (CAV3)
• Brody myopathy (ATP2A1)
• Episodic ataxia/myokymia syndrome (KCNA1)
• Hyperkalemic periodic paralysis, type 2 (SCN4A)
• Hypokalemic periodic paralysis, type 2 (SCN4A)
• Lipodystrophy, congenital generalized, type 4 (CAVIN1)
• Myasthenic syndrome, congenital, 16 (SCN4A)
• Myopathy, distal, Tateyama type (CAV3)
• Myotonia congenita, AD (CLCN1)
• Myotonia congenita, AR (CLCN1)
• Myotonia congenita, atypical, acetazolamide-responsive (SCN4A)
• Myotonia levior, AR (CLCN1)
• Myotonic dystrophy 1 (DMPK)
• Myotonic dystrophy 2 (CNBP)
• Neuromyotonia + axonal neuropathy, AR (HINT1)
• Paramyotonia congenita (SCN4A)
• Rippling muscle disease 2 (CAV3)