A case of long QT syndrome having compound mutations of KCNH2 and SCN5A

Long QT syndrome (LQTS) is a hereditary ion channelopathy resulting in prolonged cardiac repolarization and abnormal prolongation of the QT interval on the electrocardiogram (ECG). The patients are likely to develop ventricular arrhythmias and sudden cardiac death. Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. A 16-year-old-woman with QT prolongation on ECG had frequent syncopal episodes and an attack of ventricular tachycardia followed by ventricular fibrillation. The SCN5A mutation (intravene sequence 4-1 c/t) in addition to the KCNH2 mutation (Arg56Gln) was identified. Her mother and older sister were also diagnosed as having LQTS, but had only a single mutation (KCNH2). Her older sister had an episode of syncope, but her mother did not. Genetic analysis sometimes reveals 2 or more mutations in LQTS patients with clinical phenotypes of the Romano–Ward syndrome. Compound mutations in different LQTS-related genes are likely to modify clinical characteristics. In addition, comprehensive screening of LQTS-related genes might be needed when facing family members with different clinical manifestations.