Periodic paralysis is caused by mutations in ion channel genes CACNA1S, SCN4A, KCNJ2, and KCNJ18, which lead to distinct clinical features and pathogenesis important for diagnosis and tailored treatment.
Understanding the specific ion channel mutations and their corresponding electrophysiological and clinical features in periodic paralysis can guide accurate molecular diagnosis and tailored treatment strategies.
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 CACNA1S (chromosome 1q31-32), SCN4A (chromosome 17q23-25), KCNJ2 (chromosome 17q23), and KCNJ18 (chromosome 17p11.2). The common mutation sites include R528H and R1239H in CACNA1S , and R672H and T704M in SCN4A . However, there is accumulating evidence that other mutation sites in CACNA1S and SCN4A , 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.
Luo et al. (Tue,) conducted a review in Patients with periodic paralysis including familial Hypokalemic periodic paralysis, Hyperkalemic periodic paralysis, Andersen-Tawil syndrome, and thyrotoxic periodic paralysis. Periodic paralysis is caused by mutations in ion channel genes CACNA1S, SCN4A, KCNJ2, and KCNJ18, which lead to distinct clinical features and pathogenesis important for diagnosis and tailored treatment.