Familial hyperkalemic periodic paralysis caused by a de novo mutation in the sodium channel gene SCN4A

Abstract

Familial hyperkalemic periodic paralysis (HYPP) is an autosomaldominant channelopathy characterized by transient and recurrent episodes of paralysis with concomitant hyperkalemia. Mutations in the skeletal muscle voltage-gated sodium channel gene SCN4A have been reported to be responsible for this disease. Here, we report the case of a 16-year-old girl with HYPP whose mutational analysis revealed a heterozygous c.2111C>T substitution in the SCN4A gene leading to a Thr704Met mutation in the protein sequence. The parents were clinically unaffected and did not have a mutation in the SCN4A gene. A de novo SCN4A mutation for familial HYPP has not previously been reported. The patient did not respond to acetazolamide, but showed a marked improvement in paralytic symptoms upon treatment with hydrochlorothiazide. The findings in this case indicate that a de novo mutation needs to be considered when an isolated family member is found to have a HYPP phenotype.

Keywords: Hyperkalemic periodic paralysis; Mutation; SCN4A.

Fig. 1

Family pedigree and mutation analysis. (A) Pedigree of the hyperkalemic periodic paralysis (HYPP) patient shows the proband (indicated by an arrow). (B) Identification of a de novo mutation in the SCN4A gene in the HYPP patient. Electropherograms show the sequence encompassing the heterozygous transition mutation (c.2111C>T) in exon 13 of SCN4A in the patient as well as the corresponding wild-type sequences in normal family members.