Abstract 2825: A Large Chinese Family With Type-1 Short QT Syndrome
Background: The short QT syndrome (SQTS), a newly recognized and extremely rare channelopathy, is featured by short QT interval associated with increased risks of sudden death (SD). Here, we report a large Chinese SQTS family with a novel KCNH2 gene mutation identified.
Methods and Results: A asymptomatic Han Chinese man with a strong family history of SD was investigated for the suspicion of inherited arrhythmia. In 3 generations premature SD occurred in 4 family members at ages 17, 30, 40 and 48 yrs, respectively. His initial ECG showed a QTc interval of 298 ms. Ventricular fibrillation were induced by electrophysiologic study. An ICD was implanted for primary SD prevention. Ten days later the patient was shocked by inappropriate ICD discharges. After ICD re-programming no T-wave oversensing was documented during a 14-month follow-up. Analysis of candidate genes identified a C1853T substitution in KCNH2 gene encoding the IKr channel. The substitution was located in the pore region of KCNH2, resulting in a change from threonine to isoleucine at position 618 (T618I). The mutation was present in all 4 members showing a SQTS-phenotype (QTc 315±18 ms) and absent in all 6 phenotype-negative family members (QTc 412±16 ms) and 200 normal control subjects (Fig. 1⇓).
Conclusions: We report the 1st Chinese kindred with type-1 SQTS. A novel heterozygous mutation of KCNH2 is identified and the mutation cosegregates with short QT phenotype. Although multiple premature sudden death occurred in the family, all affected members have been asymptomatic. The complexity nature of SQTS is of challenging in risk stratifications and treatment strategies.