Abstract 8129: A Novel Mutation in HERG Leading to an LQTS Overlap Syndrome
Background: Although mutations and corresponding clinical characteristics of subclasses of long QT syndrome (LQTS) have been described, patients may exhibit “overlap syndromes” not corresponding neatly into classic LQTS phenotypes. Here, we report a novel mutation in the HERG potassium channel associated with LQTS.
Case presentation: A 36-year-old female with a recurrent syncope presented with loss of consciousness. There was no family or personal history of sudden cardiac death or other cardiovascular disease. Her examination was normal, except for marked sinus bradycardia (49/min). Her initial electrocardiogram (Figure A) disclosed a prolonged QTc interval (620 ms). Transthoracic echocardiography was normal. While sleeping, she had an episode of polymorphic VT (Figure B), and after temporizing with isoproterenol, she underwent implantation of a dual-chamber pacemaker-ICD, programmed for atrial pacing at 80/min. On review of her ECG, she had a broad-based T wave without notching, consistent with an LQT1 phenotype. However, her presentation of bradycardia, nocturnal episodes, and QT interval shortening with tachycardia (rate-adaptive QT shortening) suggested LQT3. We discovered a novel nonsense mutation (G208T) in the potassium channel KCNH2 (HERG), the cause of LQT2, leading to a premature stop codon near the N-terminus of KCNH2, with a non-functional gene product and reduced functional potassium channel expression. Pacing with beta-blockade normalized her QT interval by 6 months (Figure C), suggesting compensation for an altered IKr current by the IKs current (responsive to sympathetic stimulation). She has remained arrhythmia-free at 6 months.
Conclusion: We report the identification of a novel mutation in HERG leading to a LQTS syndrome. Although gene-specific clinical phenotypes are well defined in LQTS, our case identifies an unusual case of an LQTS “overlap syndrome,” with non-classical clinical, electrocardiographic, and genetic data.
- © 2011 by American Heart Association, Inc.