Objective: To verify the diagnosis of channelopathies in two families and explore the mechanism of the overlap between periodic paralysis (PP) and paramyotonia congenita (PMC). Methods: We have studied two cases with overlapping symptoms of episodic weakness and stiffness in our clinical center using a series of assessment including detailed medical history, careful physical examination, laboratory analyses, muscle biopsy, electrophysiological evaluation, and genetic analysis. Results: The first proband and part of his family with the overlap of PMC and hyperkalemic periodic paralysis (HyperPP) has been identified as c.2111C > T (T704M) substitution of the gene SCN4A. The second proband and part of his family with the overlap of PMC and hypokalemic periodic paralysis type 2 (HypoPP2) has been identified as c.4343G > A (R1448H) substitution of the gene SCN4A. In addition, one member of the second family with overlapping symptoms has been identified as a novel mutation c.2111C > T without the mutation c.4343G > A. Conclusions: SCN4A gene mutations can cause the overlap of PMC and PP (especially the HypoPP2). The clinical symptoms of episodic weakness and stiffness could happen at a different time or temperature. Based on diagnosis assessments such as medical history and muscle biopsy, further evaluations on long-time exercise test, genetic analysis, and patch clamp electrophysiology test need to be done in order to verify the specific subtype of channelopathies. Furthermore, the improvement of one member in the pregnancy period can be used as a reference for the other female in the child-bearing period with T704M.

目的：验证两个家族的通道病诊断，探讨周期性麻痹（PP）与先天性肌强直（PMC）重叠的机制。方法：我们通过一系列评估，包括详细病史，仔细的体格检查，实验室分析，肌肉活检，电生理评估和基因分析，对我们的临床中心研究了两例具有反复发作的虚弱和僵硬症状的病例。结果：该基因的第一个先证者和他的家人与PMC和高钾型周期性麻痹（HyperPP）的一部分重叠已被确定为c.2111C> T（T704M）取代SCN4A。第二先证者和他的家人与PMC的重叠和低钾性周期性麻痹2型（HypoPP2）的一部分已被鉴定为基因的c.4343G> A（R1448H）取代SCN4A。此外，第二个家族中有一个症状重叠的成员被鉴定为一种新的突变c.2111C> T，而没有突变c.4343G>A。结论：SCN4A基因突变会导致PMC和PP（尤其是HypoPP2）重叠。发作性虚弱和僵硬的临床症状可能在不同的时间或温度下发生。基于病史和肌肉活检等诊断评估，需要对长期运动测试，遗传分析和膜片钳电生理测试进行进一步评估，以验证特定的通道病亚型。此外，一个妊娠期成员的改善可以作为T704M育龄期另一位女性的参考。