Mechanisms of genetic arrhythmias: from DNA to ECG

A precise balance of ionic currents underlies normal cardiac excitation and relaxation. Disruption of this equilibrium by genetic defects, polymorphisms, therapeutic intervention, and structural abnormalities can cause arrhythmogenic phenotypes leading to syncope, seizures, and sudden cardiac death. Congenital defects result in an unpredictable expression of phenotypes with variable penetrance, even within single families. Additionally, phenotypically opposite and overlapping cardiac arrhythmogenic syndromes can even stem from the same mutation. Accordingly, the relationship between genetic mutations and clinical syndromes is becoming increasingly complex.