Idiopathic ventricular fibrillation and the V1764fsX1786 frameshift mutation of the SCN5A gene in a myotonic dystrophy type 1 patient

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 alpha-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. (C) 2020 Elsevier Ltd. All rights reserved.