Clinical features and advances in the genetics of periodic paralysis

TL;DR

Periodic paralysis is a genetic muscle disorder caused by ion channel mutations, and this review discusses its clinical features, genetic causes, and treatment implications.

Contribution

The paper reviews the current understanding of periodic paralysis, emphasizing the role of ion channel mutations and their clinical implications.

Findings

CACNA1S and SCN4A are the main genes associated with periodic paralysis, with specific mutation sites identified.

Different mutations lead to distinct pathogenesis and clinical features, affecting treatment and prognosis.

New ion channel mutations are being discovered, expanding the genetic basis of the disease.

Abstract

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.

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