Clinical, myopathological features and sodium channel α-subunit encoding gene mutation analysis in 17 patients with skeletal muscle sodium channelopathies

Objective To report the features of clinical, myopathological and sodium channel α-subunit encoding gene (SCN4A) mutations from a group of Chinese patients with skeletal muscle sodium channelopathies. Methods Seventeen cases （14 males and 3 females） from 14 families with confirmed SCN4A mutations were enrolled in this study who were diagnosed in our department from 2007 to 2012. The median age of onset was 3.0(1.0, 11.5) years. Ten patients presented with normokalemic periodic paralysis, three with hypokalemic periodic paralysis, two with paralysis periodic paramyotonia congenita, one with hyperkalemic periodic paralysis, one with paramyotonia congenita. Thirteen of them had permanent weakness. Skeletal muscle biopsies were performed in 15 and SCN4A mutation screening was performed in all patients. Results The age of onset was 2.0（1.0，4.5）years and 13.5（10.8，18.5）years respectively in patients with and without permanent weakness, indicating statistically difference between the two groups (U=1.500，P=0.002). Muscle biopsies revealed pathological changes including vacuoles or tubular aggregate in muscle fibers in 8 of 11 patients with permanent weakness，no specific change in four patients without permanent weakness. All patients were identified carrying SCN4A mutations, totally 9 different mutations, among which p.L58X, p.M403L, p.L689F and p.M1323I were novel mutations. It was noteworthy that p.T704M mutation appeared in 6 families. Conclusions SCN4A mutations can lead to heterogeneous phenotypes in Chinese patients with sodium channelopathies. Permanent weakness usually present in patients with early onset and with pathological muscle changes including vacuoles and tubular aggregates. The p.T704M mutation is the most common in the present series. Key words: Musculoskeletal disease; Channelopathies; Paralyses;  familial periodic;  NAV1.4 voltage-gated sodium channel