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Abstract：
Myotonia congenita (MC) is a rare neuromuscular disease caused by mutations within the CLCN1 gene encoding skeletal muscle chloride channels. MC is characterized by delayed muscle relaxation during contraction, resulting in muscle stiffness. There is a lack of MC case reports and data on the prevalence among Malaysians. We report a clinical case of a 50-year-old woman presents with muscle stiffness and cramp episodes that started in early childhood. She had difficulty initiating muscle movement and presented with transient muscle weakness after rest, which usually improved after repeated contraction (warm-up phenomenon). She was diagnosed with MC after myotonic discharge on electromyography (EMG). Her brother had similar symptoms; however, no additional family members showed MC symptoms. Serum creatine kinase levels were elevated in both the proband and her brother with 447 U/L and 228 U/L recorded, respectively. Genetic analysis by whole-exome sequencing (WES) revealed a previously reported pathogenic CLCN1 gene variant c.1667T>A (p.I556N). Genetic screening of all family members revealed that the same variant was observed in the children of both the proband and her brother; however, the children did not present with either clinical or electrophysiological MC symptoms. The multiplex ligation-dependent probe amplification (MLPA) analysis conducted identified neither exon deletion nor duplication in CLCN1. In conclusion, this report describes the first case of MC in Malaysia in which incomplete penetrance observed in this family is caused by a known pathogenic CLCN1 variant.
摘要：
先天性肌强直（MC）是一种罕见的神经肌肉疾病，由编码骨骼肌氯化物通道的CLCN1基因突变引起。MC的特征是收缩过程中肌肉松弛延迟，导致肌肉僵硬.缺乏关于马来西亚人患病率的MC病例报告和数据。我们报告了一例50岁女性的临床病例，其肌肉僵硬和抽筋发作始于儿童早期。她难以开始肌肉运动，休息后出现短暂的肌肉无力，这通常改善后反复收缩（热身现象）。在肌电图（EMG）上强直性放电后，她被诊断为MC。她哥哥也有类似的症状，然而，无其他家庭成员出现MC症状.先证者和她兄弟的血清肌酸激酶水平均升高，记录为447U/L和228U/L，分别。通过全外显子组测序（WES）进行的遗传分析揭示了先前报道的致病性CLCN1基因变体c.1667T>A（p。I556N)。对所有家庭成员的基因筛查显示，在先证者和她兄弟的孩子中都观察到相同的变异；然而，患儿未出现临床或电生理MC症状.进行的多重连接依赖性探针扩增(MLPA)分析在CLCN1中既不鉴定外显子缺失也不鉴定重复。总之,本报告描述了马来西亚首例MC,在该家族中观察到的不完全外显率是由已知的致病性CLCN1变异体引起的.
