Paramyotonia congenita: genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene

Abstract

Sodium channel disorders include hyperkalemic periodic paralysis (hyperPP), paramyotonia congenita (PC) and potassium-aggravated myotonia (PAM). PC is a myotonic syndrome characterized by cold-induced muscle stiffness and weakness. In this paper, we report two families. The first is affected by PC with cold-induced stiffness and no weakness, in addition to hyperPP. This family displays the Arg1448Cys mutation in the sodium channel gene originally described in pure PC families. The fact that families with the same mutation present distinct phenotypes indicates that other factors, genetic or environmental, may modulate the expression of the disease in sodium channel disorders. The second family was unusual because patients presented cold-induced weakness without stiffness. A mutation was found in the sodium channel gene that changed an isoleucine into a threonine at position 693. These two families demonstrate that sodium channel mutations may cause either cold-induced stiffness or weakness.