Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome

Ilan Goldenberg, Arthur J. Moss, Wojciech Zareba, Scott Mcnitt, Jennifer L. Robinson, Ming Qi, Jeffrey A. Towbin, Michael John Ackerman, Laura Murphy

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1161-1168
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume17
Issue number11
DOIs
StatePublished - Nov 2006

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Jervell-Lange Nielsen Syndrome
Romano-Ward Syndrome
Long QT Syndrome
Defibrillators
Registries
Therapeutics
Parturition

Keywords

  • Arrhythmia
  • Genetics
  • Long-QT syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. / Goldenberg, Ilan; Moss, Arthur J.; Zareba, Wojciech; Mcnitt, Scott; Robinson, Jennifer L.; Qi, Ming; Towbin, Jeffrey A.; Ackerman, Michael John; Murphy, Laura.

In: Journal of Cardiovascular Electrophysiology, Vol. 17, No. 11, 11.2006, p. 1161-1168.

Research output: Contribution to journalArticle

Goldenberg, Ilan ; Moss, Arthur J. ; Zareba, Wojciech ; Mcnitt, Scott ; Robinson, Jennifer L. ; Qi, Ming ; Towbin, Jeffrey A. ; Ackerman, Michael John ; Murphy, Laura. / Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. In: Journal of Cardiovascular Electrophysiology. 2006 ; Vol. 17, No. 11. pp. 1161-1168.
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AU - Moss, Arthur J.

AU - Zareba, Wojciech

AU - Mcnitt, Scott

AU - Robinson, Jennifer L.

AU - Qi, Ming

AU - Towbin, Jeffrey A.

AU - Ackerman, Michael John

AU - Murphy, Laura

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AB - 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.

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