title: Jervell and Lange-Nielsen syndrome in a father and daughter from a large highly inbred family: a 16-year follow-up of 59 living members.
abstract: OBJECTIVE
  To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred.
  
  
  METHODS
  A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years.
  
  
  RESULTS
  A total of 24 living members were affected--QTc: 480-680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only β-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period.
  
  
  CONCLUSIONS
  Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.
authors.affiliation: Pediatric Cardiology Unit, JFK Medical Center, Edison, New Jersey, United States of America. kapilkumar90@gmail.com
authors.forename: Shyamal Kumar
authors.initials: SK
authors.lastname: Sanyal
authors.forename: Kanwar K
authors.initials: KK
authors.lastname: Kaul
authors.forename: Akhtar
authors.initials: A
authors.lastname: Hussein
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilroy
authors.forename: Kisan
authors.initials: K
authors.lastname: Agarwal
authors.forename: Saira
authors.initials: S
authors.lastname: Sohel
mesh_terms: D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D016757:Death, Sudden, Cardiac / Q000209:etiology; D018450:Disease Progression; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics; D006323:Heart Arrest / Q000209:etiology / Q000235:genetics*; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013575:Syncope / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D016171:Torsades de Pointes / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology