Brugada syndrome in spinal and bulbar muscular atrophy

Objective: The aim of this study was to clarify myocardial involvement and its clinical implications in subjects with spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease affecting both neuronal and nonneuronal tissues. Methods: Two independent cardiologists evaluated ECGs from a total of 144 consecutive subjects with SBMA. We performed immunohistochemical, immunoblot, and quantitative real-time PCR analyses of autopsied myocardium. Results: Abnormal ECGs were detected in 70 (48.6%) of 144 subjects. The most frequent findings were ST-segment abnormalities in V_1-3 (19.4%), followed by ST-segment abnormalities in V_5-6 (18.1%). We detected Brugada-type ECGs in 17 of 28 subjects with ST-segment abnormalities in V_1-3. Of those, one subject presented with syncope that required an implantable cardioverter defibrillator and led to eventual sudden death, and another subject also died suddenly. No subjects with Brugada-type ECGs had mutations in SCN5A, CACNA1C, or CACNB2 genes. In autopsied cases, we detected nuclear accumulation of the mutant androgen receptor protein and decreased expression levels of SCN5A in the myocardium. Conclusions: Subjects with SBMA often show Brugada-type ECG. The accumulation of the pathogenic androgen receptor may have a role in the myocardial involvement in SBMA.