Genetics of Channelopathy: Familial Periodic Paralysis

J Korean Neurol Assoc > Volume 23(6); 2005 > Article

Journal of the Korean Neurological Association 2005;23(6): 737-744.

채널병의 유전학: 가족형주기성마비

전남대학교 의과대학 신경과학교실

Genetics of Channelopathy: Familial Periodic Paralysis

Myeong-Kyu Kim

Department of Neurology, Chonnam National University Medical School, Gwangju, Korea

Abstract

Familial periodic paralysis (FPP) is inherited as a dominant trait, and the intermittent failure to maintain the skeletal muscle resting potential is due to mutations in the genes coding for the voltage-gated ion channels. Because several variants of FPP have been delineated on the bases of clinical features, the expectation was that these variants might be due to involvement of different classes of ion channels. The reality of the situation has proven to be more complicated. Mutation-induced defects in the same channel may give rise to diverse phenotypes (phenotypic heterogeneity) and, conversely, mutation in different channel genes may produce a common phenotype (genetic heterogeneity). Regardless of which type of ion channel is defective, the final common pathway is the depolarization-induced loss of muscle excitability; gain-of-function defect in voltage-gated Na channel may cause myotonia, periodic paralysis or both, clinical features of hyperkalemic periodic paralysis and paramyotonia congenita, and loss-of-function defects in voltage-gated Na and Ca channel and K channel may be responsible for periodic paralysis, cardiac arrhythmia or both in hypokalemic periodic paralysis or Andersen's syndrome, respectively. This review focuses on the clinical features, molecular genetic defects, and pathophysiologic mechanisms that underlie FPP.KeyWords:Familial periodic paralysis, Voltage-gated ion channel, Channelopathy, Genetics