Clinical features and advances in the genetics of periodic paralysis

Periodic paralysis (PP) is a group of ion channel diseases with incomplete autosomal dominant inheritance, except in sporadic patients. Ion channel gene mutations cause transient abnormalities in skeletal muscle excitability and muscle weakness. Different mutation sites cause different pathogenesis, which is very important for the classification, clinical manifestations, treatment and prognosis of periodic paralysis. Currently, the recognized mutated genes are <i>CACNA1S</i> (chromosome 1q31-32), <i>SCN4A</i> (chromosome 17q23-25), <i>KCNJ2</i> (chromosome 17q23), and <i>KCNJ18</i> (chromosome 17p11.2). The common mutation sites include R528H and R1239H in <i>CACNA1S</i>, and R672H and T704M in <i>SCN4A</i>. However, there is accumulating evidence that other mutation sites in <i>CACNA1S</i> and <i>SCN4A</i>, and even new ion channel mutations may induce periodic paralysis. Their different pathogenesis, clinical features and therapeutic measures have been widely described. This review will introduce the clinical manifestations of periodic paralysis, the different mutation sites of each ion channel, and the pathogenesis. Based on the clinical types of periodic paralysis, the characteristics of the latter are further discussed.