A family of hypokalemic periodic paralysis with CACNA1S gene mutation showing incomplete penetrance in women.

Familial hypokalemic periodic paralysis is an autosomal dominant genetic muscle disease characterized by periodic attacks of muscle weakness associated with a decrease in serum potassium. There are two major missense mutation sites in the calcium channel alpha1 subunit (CACNA1S) gene in these patients. We recently encountered a 13-year-old Japanese boy who had collapsed following exercise and was found to have a low serum potassium level. Clinical and genetic studies including exploration of his family tree proved that he and his maternal relatives had the disease with the missense mutation, Arg528His (CGC --> CAC). However, his mother and grandmother had no symptoms of the disease, indicating reduced penetrance in female carriers. Sexual difference in the penetrance of this disease and the association between the clinical symptoms and the types of genetic defects are discussed.