Myotonia, defined as delayed relaxation of muscle after contraction, is seen in a group of
genetic disorders that includes autosomal dominant
myotonia congenita (
Thomsen's disease) and autosomal recessive
myotonia congenita (Becker's disease). Both disorders are characterized electrophysiologically by increased excitability of muscle fibers, reflected in clinical
myotonia. These diseases are similar except that transient weakness is seen in patients with Becker's, but not
Thomsen's disease. Becker's and Thomsen's diseases are caused by mutations in the skeletal muscle voltage-gated
chloride channel gene (CLCN1). Genetic screening of a panel of 18 consecutive
myotonia congenita (MC) probands for mutation in CLCN1 revealed that a novel Gln-68-Stop
nonsense mutation predicts premature truncation of the
chloride channel protein. Four previously reported mutations, Arg-894-stop, Arg-338-Gln, Gly-230-Glu, and del 1437-1450, were also noted in our sample set. The Arg-338-Gln and Gly-230-Glu mutations were found in patients with different phenotypes from those of previous reports. Further study of the Arg-338-Gln and Gln-230-Glu alleles may shed light on variable modes of transmission (dominant versus recessive) in different families. Physiologic study of these mutations may lead to better understanding of the pathophysiology of
myotonia in these patients and of voltage-gated
chloride channel structure/function relationships in skeletal muscles.