Published online before print February 6, 2006, doi: 10.1161/CIRCULATIONAHA.105.592899
(Circulation. 2006;113:783-790.)
© 2006 American Heart Association, Inc.
Arrhythmia/Electrophysiology |
The Jervell and Lange-Nielsen Syndrome
Natural History, Molecular Basis, and Clinical Outcome
From the Department of Cardiology, University of Pavia and IRCCS Policlinico S. Matteo, Pavia, Italy (P.J.S., C.S., L.C.); Molecular Cardiology Laboratory, IRCCS Policlinico S. Matteo, Pavia, Italy (P.J.S., L.C.); Department of Cardiology, St Olavs Hospital HF, University Hospital of Trondheim, Trondheim, Norway (J.B.); Medical Outpatient Clinic, Rikshospitalet, Oslo, Norway (J.P.A.); Hughes Medical Institute, Department of Cardiology and Cell Biology, Children’s Hospital, Harvard Medical School, Boston, Mass (K.T.); Russian Center for Children’s Arrhythmias, Moscow Institute of Pediatric and Pediatric Surgery, Moscow, Russia (M.S.); Department of Cardiology, Children’s Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston, Mass (C.I.B.); Unit of Clinical and Molecular Genetics, Institute of Child Health, University College London, London, UK (M.B.-G.); Department of Cardiology, Helsinki University Hospital, Helsinki, Finland (L.T.); Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan (M.H.); Leibniz Institute for Arteriosclerosis Research at the University of Münster, Molecular Cardiology, and Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany (E.S.-B.); and Cardiology Department, Hopital Lariboisiere, Paris, France; INSERM U582, IFR 14, Groupe Hospitalier Pitié-Salpétrière, Paris, France; and Centre de cardiologie infantile, Les Loges en Josas, France (I.D.).
Correspondence to Peter J. Schwartz, MD, Department of Cardiology, IRCCS Policlinico S. Matteo, Viale Golgi 19-27100 Pavia, Italy. E-mail pjqt{at}compuserve.com
Received October 3, 2005; revision received November 4, 2005; accepted November 18, 2005.
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. ß-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 ß-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.
CLINICAL PERSPECTIVE
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