Abstract 12477: Clinical Differences Between KCNH2 and SCN5A Mutation Carriers with Brugada Syndrome and Brugada-Like ECG Patients in Japan
Background: Brugada syndrome (BrS) is an inherited disease associated with malignant arrhythmias and cardiac sudden deaths. Among the causative genes in BrS, SCN5A mutations were most frequently reported, and its genotype-phenotype correlations were investigated in detail. On the other hand, though some of the KCNH2 variants were identified in patients with BrS or Brugada-like ECG, their clinical characteristics remain unknown. Functional analyses of the reported KCNH2 variants mainly displayed gain of function, which turned out to cause the coved type ST elevation. The clinical differences between KCNH2 and SCN5A mutation carriers, however, have not been elucidated yet.
Methods and Results: We screened KCNH2 and SCN5A gene mutations in 207 Japanese patients from different families with BrS or Brugada-like ECG. Among them, we identified 3 KCNH2 and 14 SCN5A mutations. No patients carried both of the KCNH2 and SCN5A mutation. All the KCNH2 variants were missence change. On the other hand, the mutations in SCN5A were 8 missence, 3 nonsense and 3 frame shift changes. In SCN5A mutation carriers, the frequency of the syncope or the cardiac arrest was higher (n=6, 43%) compared to KCNH2 variant carriers (n=0). Concerning to the ECG characteristics, coved type ST elevation in ECG was detected in 2 of 3 KCNH2 variant carriers (67%), and 6 of 14 SCN5A mutation carriers (43%). QRS durations in SCN5A mutation carriers were significantly longer (114.9±3.2 ms) compared to those of KCNH2 variants carriers (79.0±3.8 ms, p<0.01). Though QTc time were shorter in KCNH2 variants carriers (360.1±23.9 ms), there was no significant difference compare to those of SCN5A mutation carriers (401.6±8.9 ms).
Conclusions: Here we report the clinical differences between KCNH2 and SCN5A mutation carriers in patients with BrS or Brugada-like ECG. The carriers of KCNH2 variants displayed mild clinical phenotypes and shorter QRS duration compare to SCN5A mutation carriers.
- © 2011 by American Heart Association, Inc.