title: Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome.
abstract: BACKGROUND
  Data regarding risk factors and clinical course of patients affected with Jervell and Lange-Nielsen syndrome (JLNS), an autosomal recessive form of the congenital long-QT syndrome (LQTS), are limited to several reported cases and a retrospective analysis.
  
  
  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 > or = 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.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA. Ilan.Goldenberg@heart.rochester.edu
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robinson
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: Laura
authors.initials: L
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017147:Defibrillators, Implantable; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D029593:Jervell-Lange Nielsen Syndrome / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000319:Adrenergic beta-Antagonists