To explore the clinical and genetic characteristics of five families with primary periodic
paralysis (PPP). We reviewed clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, and genetic analysis from five families with PPP. Five families with PPP included:
hypokalemic periodic paralysis type 1 (HypoPP1, CACNA1S, 1/5),
hypokalemic periodic paralysis type 2 (HypoPP2, SCN4A, 2/5),
normokalemic periodic paralysis (NormoPP, SCN4A, 1/5), and
Andersen-Tawil syndrome (ATS, KCNJ2, 1/5). The basic clinical manifestations of five families were consistent with PPP, presenting with paroxysmal
muscle weakness, with or without abnormal serum
potassium. ATS was accompanied by ventricular arrhythmias, and skeletal and craniofacial anomalies, developing with a permanent fixed
myopathy later. The electromyography showed diffuse myopathic discharge, and muscle biopsy showed tubular aggregates. Genetic testing revealed five families with PPP carried CACNA1S (R1242S), SCN4A (R675Q, T704M), and KCNJ2 (R218Q) respectively. The novel heterozygous R1242S mutation in CACNA1S caused a conformational change in the
protein structure, and the
amino acid of this mutation site was highly conserved among different species. SCN4A mutations led to two phenotypes of HypoPP2 and NormoPP. PPPs are autosomal dominant disorders of
ion channel dysfunction characterized by episodic flaccid
muscle weakness secondary to abnormal sarcolemmal excitability. PPPs are caused by mutations in skeletal muscle
calcium channel CaV1.1 gene (CACNA1S),
sodium channel NaV1.4 gene (SCN4A), and
potassium channels Kir2.1, Kir3.4 genes (KCNJ2, KCNJ5), including HypoPP1, HypoPP2, NormoPP,
HyperPP, and ATS, which have significant clinical and genetic heterogeneity. Diagnosis is based on the characteristic clinical presentation then confirmed by genetic testing.