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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

Published online by Cambridge University Press:  13 May 2013

Shyamal Kumar Sanyal ,
Kanwar K. Kaul ,
Akhtar Hussein ,
Robert S. Wilroy ,
Kisan Agarwal  and
Saira Sohel
Shyamal Kumar Sanyal*
Affiliation:
Pediatric Cardiology Unit, JFK Medical Center, Edison, New Jersey, United States of America
Kanwar K. Kaul
Affiliation:
Department of Pediatrics, University of Tennessee, Memphis, Tennessee, United States of America
Akhtar Hussein
Affiliation:
Division of Adult Cardiology, Department of Internal Medicine, King Faisal University College of Medicine and Medical Sciences, Dammam, Kingdom of Saudi Arabia
Robert S. Wilroy
Affiliation:
Division of Genetics, Department of Pediatrics, University of Tennessee, Memphis, Tennessee, United States of America
Kisan Agarwal
Affiliation:
Pediatric Cardiology, JFK Medical Center, Edison, New Jersey, United States of America
Saira Sohel
Affiliation:
Pediatric Cardiology Unit, JFK Medical Center, Edison, New Jersey, United States of America
*
Correspondence to: Dr Shyamal Kumar Sanyal, MA1/7-GD, Garden Estate, Gurgaon (Haryana), INDIA, 122002. Tel: 0091 124 4062676; E-mail: kapilkumar90@gmail.com
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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. Method: 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. Conclusion: 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.

Keywords

Autosomal dominantTorsades de Pointessyncopecardiac arrestsudden death
Type
Original Articles
Information
Cardiology in the Young , Volume 23 , Issue 4 , August 2013 , pp. 530 - 539
Copyright
Copyright © Cambridge University Press 2013 

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