The Jervell and Lange-Nielsen syndrome: Natural history, molecular basis, and clinical outcome

Peter J. Schwartz, Carla Spazzolini, Lia Crotti, Jørn Bathen, Jan P. Amlie, Katherine Timothy, Maria Shkolnikova, Charles I. Berul, Maria Bitner-Glindzicz, Lauri Toivonen, Minoru Horie, Eric Schulze-Bahr, Isabelle Denjoy

Research output: Contribution to journalArticle

Abstract

Background - Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the IKs current, are still based largely on case reports. Methods and Results - We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptomatic by age 3. Their QTc was markedly prolonged (557±65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc >550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. β-Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had CA/SD. Conclusions - J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which β-blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc ≤550 ms, those without events in the first year of life, and those with mutations on KCNE1. Early therapy with implanted cardioverter/defibrillators must be considered.

Original languageEnglish
Pages (from-to)783-790
Number of pages8
JournalCirculation
Volume113
Issue number6
DOIs
Publication statusPublished - Feb 2006

Keywords

  • Arrhythmia
  • Death, sudden
  • Electrocardiography
  • Heart arrest
  • Long-QT syndrome

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Schwartz, P. J., Spazzolini, C., Crotti, L., Bathen, J., Amlie, J. P., Timothy, K., Shkolnikova, M., Berul, C. I., Bitner-Glindzicz, M., Toivonen, L., Horie, M., Schulze-Bahr, E., & Denjoy, I. (2006). The Jervell and Lange-Nielsen syndrome: Natural history, molecular basis, and clinical outcome. Circulation, 113(6), 783-790. https://doi.org/10.1161/CIRCULATIONAHA.105.592899