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.