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Abstract：
BACKGROUND: Becker\'s type myotonia congenita is an autosomal recessive nondystrophic skeletal muscle disorder characterized by muscle stiffness and the inability of muscle relaxation after voluntary contraction. It is caused by mutations in the CLCN1 gene, which encodes for a chloride channel mainly expressed in the striated muscle. Most cases have been reported in the European population, and only mexiletine has demonstrated a randomized placebo-controlled, double-blinded effectiveness.
METHODS: We present two male siblings from Colombia with Latino ancestry, without parental consanguinity, with myotonia during voluntary movements, muscle hypertrophy of lower extremities, transient weakness, and severe muscle fatigue after exercise from three years of age. A genetic panel for dystrophic muscle disorders and a muscle biopsy were both negative. Genetic testing was performed in their second decade of life. Both patients\' exomic sequencing test reported the mutation c.1129C >T (p.Arg377*) affecting exon 10 of the CLCN1, generating a premature stop codon. This mutation was described as pathogenic and observed in only one other patient in the United Kingdom.
CONCLUSIONS: To our knowledge, these are the first cases of Becker\'s type myotonia congenita reported in Colombia. Increasing awareness of healthcare providers for this type of disease in the region could lead to the identification of undiagnosed patients. Limited availability of medical geneticists as well as genetic testing may be the cause of the lack of previous description of cases, in addition to the delay in the diagnosis of the patients. Further epidemiological studies can reveal underdiagnosed myotonias in the country and in the Latin-American region.
METHODS: We present two male siblings from Colombia with Latino ancestry, without parental consanguinity, with myotonia during voluntary movements, muscle hypertrophy of lower extremities, transient weakness, and severe muscle fatigue after exercise from three years of age. A genetic panel for dystrophic muscle disorders and a muscle biopsy were both negative. Genetic testing was performed in their second decade of life. Both patients\' exomic sequencing test reported the mutation c.1129C >T (p.Arg377*) affecting exon 10 of the CLCN1, generating a premature stop codon. This mutation was described as pathogenic and observed in only one other patient in the United Kingdom.
CONCLUSIONS: To our knowledge, these are the first cases of Becker\'s type myotonia congenita reported in Colombia. Increasing awareness of healthcare providers for this type of disease in the region could lead to the identification of undiagnosed patients. Limited availability of medical geneticists as well as genetic testing may be the cause of the lack of previous description of cases, in addition to the delay in the diagnosis of the patients. Further epidemiological studies can reveal underdiagnosed myotonias in the country and in the Latin-American region.
摘要：
背景：Becker型先天性肌强直是一种常染色体隐性遗传的非营养不良性骨骼肌疾病，其特征是肌肉僵硬和自愿收缩后肌肉不能松弛。它是由CLCN1基因突变引起的，其编码主要在横纹肌中表达的氯离子通道。大多数病例是在欧洲人口中报告的，只有美西律证明了随机安慰剂对照，双盲有效性。
方法：我们介绍了两个来自哥伦比亚的拉丁裔男性兄弟姐妹，没有父母的血缘关系，在自愿运动期间出现肌强直，下肢肌肉肥大，短暂性弱点,从三岁开始锻炼后严重的肌肉疲劳。营养不良性肌肉疾病的遗传小组和肌肉活检均为阴性。基因检测是在他们生命的第二个十年进行的。两名患者的外显子组测序测试报告突变c.1129C>T（p。Arg377*）影响CLCN1的外显子10，产生过早的终止密码子。这种突变被描述为致病性的，并且仅在英国的另一位患者中观察到。
结论：据我们所知，这是哥伦比亚报道的首例Becker型先天性肌强直症。该地区医疗保健提供者对此类疾病的认识不断提高，可能会导致识别未确诊的患者。有限的医学遗传学家以及基因检测可能是缺乏以前的病例描述的原因，除了病人的诊断延迟。进一步的流行病学研究可以揭示该国和拉丁美洲地区未确诊的肌张力障碍。
方法：我们介绍了两个来自哥伦比亚的拉丁裔男性兄弟姐妹，没有父母的血缘关系，在自愿运动期间出现肌强直，下肢肌肉肥大，短暂性弱点,从三岁开始锻炼后严重的肌肉疲劳。营养不良性肌肉疾病的遗传小组和肌肉活检均为阴性。基因检测是在他们生命的第二个十年进行的。两名患者的外显子组测序测试报告突变c.1129C>T（p。Arg377*）影响CLCN1的外显子10，产生过早的终止密码子。这种突变被描述为致病性的，并且仅在英国的另一位患者中观察到。
结论：据我们所知，这是哥伦比亚报道的首例Becker型先天性肌强直症。该地区医疗保健提供者对此类疾病的认识不断提高，可能会导致识别未确诊的患者。有限的医学遗传学家以及基因检测可能是缺乏以前的病例描述的原因，除了病人的诊断延迟。进一步的流行病学研究可以揭示该国和拉丁美洲地区未确诊的肌张力障碍。
