Pediatric cohort with long QT syndrome – KCNH2 mutation carriers present late onset but severe symptoms –

Background: In children with long QT syndrome (LQTS), risk factors for cardiac events have been reported, but age-, gender- and genotype-related differences in prognosis remain unknown in Asian countries. Methods and Results: The study examined clinical prognosis at age between 1 and 20 years in 496 LQTS patients who were genotyped as either of LQT1–3 (male, n=206). Heterozygous mutations were observed in 3 major responsible genes: KCNQ1 in 271, KCNH2 in 192, and SCN5A in 33 patients. LQTS-associated events were classified into 3 categories: (1) syncope (n=133); (2) repetitive torsade de pointes (TdP, n=3); and (3) cardiopulmonary arrest (CPA, n=4). The risk of cardiac events was significantly lower in LQT1 girls than boys≤12 years (HR, 0.55), whereas LQT2 female patients ≥13 years had the higher risk of cardiac events than male patients (HR, 4.60). Patients in the repetitive TdP or CPA group included 1 LQT1 female patient, 1 LQT2 male patient, and 5 LQT2 female patients. All LQT2 patients in these groups had TdP repeatedly immediately after the antecedent event. In addition, all 5 female LQT2 patients in these groups had the event after or near puberty. Conclusions: Female LQT2 children might have repeated TdP shortly after prior events, especially after puberty.