Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
J Clin Neurosci. 2020 Apr;74:242-244. doi: 10.1016/j.jocn.2020.02.007. Epub 2020 Feb 13.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited muscular dystrophy caused by an expanded CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. Cardiac involvements in DM1 are characterized by cardiac conduction delays and atrial or ventricular tachycardia, which increase the risk of sudden cardiac death when compared with general population. Only a few reports have investigated the association between DM1 and inherited arrhythmias, including Brugada syndrome and a splicing abnormality of the SCN5A gene, encodes the α-subunit of cardiac voltage-gated Na+ channels. Here we report a 24-year-old male patient with progressive grip myotonia and dysphagia, who was genetically diagnosed with idiopathic ventricular fibrillation (IVF) caused by a novel V1764fsX1786 frameshift mutation in the SCN5A gene at the age of 18 years. Family history was negative for arrhythmia, cardiac sudden death, and neuromuscular disorders. Genetic analysis using the Southern blot technique revealed 350 CTG repeats in the DMPK gene. This is the first case of DM1 with genetically confirmed overlapping CTG repeat expansion and a V1764fsX1786 frameshift mutation in the SCN5A gene. Our case suggests that a loss-of-function in the cardiac sodium channel may contribute to the cardiac complications in DM1 patients.
1 型肌强直性营养不良(DM1)是一种常染色体显性遗传性肌肉疾病,由肌强直性营养不良蛋白激酶(DMPK)基因中的 CTG 重复扩展引起。DM1 的心脏受累表现为心脏传导延迟和心房或室性心动过速,与一般人群相比,增加了心脏性猝死的风险。只有少数报道研究了 DM1 与遗传性心律失常之间的关系,包括 Brugada 综合征和 SCN5A 基因剪接异常,该基因编码心脏电压门控 Na+通道的α亚单位。在这里,我们报告了一名 24 岁男性患者,表现为进行性握力肌强直性和吞咽困难,他在 18 岁时被基因诊断为特发性室颤(IVF),由 SCN5A 基因中的新型 V1764fsX1786 移码突变引起。家族史无心律失常、心脏性猝死和神经肌肉疾病。使用 Southern blot 技术进行的基因分析显示 DMPK 基因中有 350 个 CTG 重复。这是首例 DM1 患者具有重叠 CTG 重复扩展和 SCN5A 基因 V1764fsX1786 移码突变的基因确诊病例。我们的病例表明,心脏钠离子通道的功能丧失可能导致 DM1 患者的心脏并发症。