In patients with myotonic dystrophy type 1 (DM1), the mechanisms underlying sudden cardiac death, which occurs in up to 1/3 of patients, are unclear. To study the potential role of Brugada syndrome in ventricular tachyarrhythmias and sudden death in DM1 patients, 914 adult patients included in the DM1 Heart Registry during 2000-2009 were screened for the presence of type 1 Brugada pattern on electrocardiogram (ECG). Direct sequencing of SCN5A was also performed in patients with Brugada pattern. Further, SCN5A splicing on ventricular myocardial specimens harvested during cardiac transplantation in a 45-year-old patient with DM1 and three controls with inherited dilated cardiomyopathy were analysed. A type 1 Brugada pattern was present on the ECG of seven of 914 patients (0.8%), including five with a history of sustained ventricular tachyarrhythmia or sudden death, who fulfilled the criteria for Brugada syndrome. SCN5A sequencing was normal in all patients. Ventricular myocardial specimen analysis displayed abnormal splicing of SCN5A exon 6, characterised by over-expression of the ‘neonatal’ isoform, called exon 6A, in the patient with DM1, but not from the controls. These results suggest a potential implication of Brugada syndrome in sudden death in DM1, which may be related to missplicing of SCN5A, and provide a new insight into the pathophysiology of heart disease in DM1.
