In a father and daughter (family SCM8) with potassium-aggravated myotonia (608390) without muscle weakness, Heine et al. (1993) identified a heterozygous c.4765G-A transition in exon 24 of the SCN4A gene, predicted to result in a val1589-to-met (V1589M) substitution. The family had previously been reported by Iaizzo et al. (1991) as family MyC2. The myotonia in this family was aggravated by both cold and potassium loading, similar to paramyotonia congenita (PMC; 168300). The mutation is located within transmembrane segment S6 of channel repeat IV close to the cytoplasmic surface, a region thought to act as acceptor of the inactivation gate of the channel. An increase in the number of noninactivating sodium channels had been demonstrated in earlier electrophysiologic studies on excised muscle from the index patient. The nearby M1592V (603967.0002) mutation causes hyperkalemic periodic paralysis (170500) of the myotonic, nondystrophic form.
Orrell et al. (1998) identified the V1589M mutation in a family in which 9 members spanning 4 generations had cramps in the fingers, toes, and eyelids, consistent with potassium-aggravated myotonia. A reduction in amplitude of compound muscle action potential on cooling and administration of potassium was demonstrated. The authors noted that the phenotype in this family was milder than that in the family reported by Heine et al. (1993).
