Identification of a SCN5A Genetic Variant Associated With Type 1 Brugada Syndrome (BrS) in a Family.

ABSTRACT

The Brugada pattern is associated with a genetic disorder characterized by ST-segment elevation in the right precordial leads on electrocardiogram (EKG) in the absence of structural heart disease. Patients with the Brugada pattern have an increased risk for ventricular tachyarrhythmia and sudden cardiac death. Loss-of-function mutations in the SCN5A gene which encodes the alpha subunit of the cardiac sodium channel have been associated with Brugada syndrome (BrS). We report a case of a patient who was found to have a spontaneous type 1 Brugada pattern on a routine EKG done prior to travel. He underwent electrophysiological testing (EPS) which provoked ventricular tachycardia and underwent implantable cardioverter defibrillator (ICD) placement. His family history revealed a history of sudden cardiac death, abnormal EKG, syncope, dilated cardiomyopathy, and BrS. Genetic testing revealed a variant of uncertain significance (VUS) in the SCN5A gene in the proband and six of his relatives. The SCN5A VUS in this clinical context and segregation with the disease in his family supports its reclassification to pathogenic.