This study was supported in part by research grants HL-33843 and HL-51618 from the National Institutes of Health, Bethesda, MD.
Clinical Course and Risk Stratification of Patients Affected with the Jervell and Lange-Nielsen Syndrome
Article first published online: 14 AUG 2006
Journal of Cardiovascular Electrophysiology
Volume 17, Issue 11, pages 1161–1168, November 2006
How to Cite
GOLDENBERG, I., MOSS, A. J., ZAREBA, W., MCNITT, S., ROBINSON, J. L., QI, M., TOWBIN, J. A., ACKERMAN, M. J. and MURPHY, L. (2006), Clinical Course and Risk Stratification of Patients Affected with the Jervell and Lange-Nielsen Syndrome. Journal of Cardiovascular Electrophysiology, 17: 1161–1168. doi: 10.1111/j.1540-8167.2006.00587.x
Dr. Ackerman serves as a consultant for Clinical Data (formerly Genaissance Pharmaceuticals). The Mayo Foundation for Medical Education & Research receives royalties from Clinical Data for the intellectual property utilized in their Familion QTS genetic test.
Manuscript received 14 April 2006; Revised manuscript received 8 June 2006; Accepted for publication 21 June 2006.
- Issue published online: 14 AUG 2006
- Article first published online: 14 AUG 2006
- long-QT syndrome;
Introduction: Data regarding risk factors and clinical course of patients affected with Jervell and Lange-Nielsen syndrome (JLNS), an autosomal recesssive form of the congenital long-QT syndrome (LQTS), are limited to several reported cases and a retrospective analysis.
Methods and Results: We prospectively followed-up 44 JLNS patients from the U.S. portion of the International LQTS Registry and compared their clinical course with 2,174 patients with the phenotypically determined dominant form of LQTS (Romano-Ward syndrome [RWS]) and a subgroup of 285 patients with type 1 LQTS (LQT1). Mean (±SD) corrected QT interval (QTc) in the JLNS, RWS, and LQT1 groups were 548 ± 73, 500 ± 48, and 502 ± 46 msec, respectively (P < 0.001). The cumulative rates of cardiac events from birth through age 40 among JLNS and RWS patients were 93% (mean [±SD] age: 5.0 ± 7.0 years) and 54% (mean [±SD] age: 14.2 ± 9.3 years), respectively (P < 0.001). The JLNS:RWS and JLNS:LQT1 adjusted hazard ratios (HR) for cardiac events were highest among patients with a baseline QTc ≥550 msec (HR = 15.83 [P < 0.001] and 13.80 [P < 0.001], respectively). Among JLNS patients treated with beta-blockers, the cumulative probability of LQTS-related death was 35%; defibrillator therapy was associated with a 0% mortality rate during a mean (±SD) follow-up period of 4.9 ± 3.4 years.
Conclusions: Patients with JLNS experience a high rate of cardiac and fatal events from early childhood despite medical therapy. Defibrillator therapy appears to improve outcome in this high-risk population, although longer follow-up is needed to establish its long-term efficacy.