A novel muscle sodium channel mutation causes painful congenital myotonia

✍ Scribed by Dr. Jeffrey Rosenfeld; Karen Sloan-Brown; Alfred L. George Jr

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 424 KB
• Volume: 42
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.410420520

✦ Synopsis

Mutations in the skeletal muscle voltage-gated sodium channel alpha-subunit gene (SCN4A) have been associated with a spectrum of inherited nondystrophic myotonias and periodic paralyses. Most disease-associated SCN4A alleles occur in portions of the gene that encode the third and fourth repeat domains with the conspicuous absence of mutations in domain 1. Here we describe a family segregating an unusual autosomal dominant congenital myotonia associated with debilitating pain especially severe in the intercostal muscles. A novel SCN4A mutation causing the replacement of Val445 in the sixth transmembrane segment of domain 1 with methionine was discovered in all affected individuals and is the likely genetic basis for the syndrome. Myotonia was resistant to treatment; however, the most severely affected family member responded dramatically to the sodium channel blocking agent flecainide.