探讨原发性周期性麻痹(PPP)5个家系的临床和遗传特征。我们回顾了临床表现,实验室结果,心电图,肌电图,肌肉活检,和五个PPP家族的遗传分析。PPP的五个家庭包括:低钾性周期性麻痹1型(HypoPP1,CACNA1S,1/5),低钾性周期性麻痹2型(HypoPP2,SCN4A,2/5),降钾性周期性麻痹(NormoPP,SCN4A,1/5),和Andersen-Tawil综合征(ATS,KCNJ2,1/5)。5个家庭的基本临床表现与PPP一致,表现为阵发性肌肉无力,有或没有异常的血清钾。ATS伴有室性心律失常,骨骼和颅面异常,后来发展为永久性固定肌病。肌电图显示弥漫性肌病放电,肌肉活检显示管状聚集体。基因检测显示,五个PPP家族携带CACNA1S(R1242S),SCN4A(R675Q,T704M),和KCNJ2(R218Q)。CACNA1S中的新杂合R1242S突变引起蛋白质结构的构象变化,该突变位点的氨基酸在不同物种中高度保守。SCN4A突变导致HypoPP2和NormoPP两种表型。PPPs是离子通道功能障碍的常染色体显性疾病,其特征是继发于异常肌膜兴奋性的偶发性弛缓性肌肉无力。PPPs是由骨骼肌钙通道CaV1.1基因(CACNA1S)突变引起的,钠通道NaV1.4基因(SCN4A),和钾通道Kir2.1,Kir3.4基因(KCNJ2,KCNJ5),包括HypoPP1,HypoPP2,NormoPP,HyperPP,和ATS,具有显著的临床和遗传异质性。诊断基于特征性临床表现,然后通过基因检测确认。
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.