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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: [email protected]
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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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References

1. Jervell, A, Lange-Nielsen, F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death. Am Heart J 1957; 54: 59–68.Google Scholar
2. Schulze-Bahr, E, Haverkamp, W, Wedekind, H, et al. Autosomal recessive long-QT syndrome (Jervell Lange-Nielsen syndrome) is genetically heterogeneous. Hum Genet 1997; 100: 573–576.CrossRefGoogle ScholarPubMed
3. Schwartz, PJ, Spazzolini, C, Crotti, L, et al. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation 2006; 113: 783–790.CrossRefGoogle ScholarPubMed
4. Goldenberg, I, Moss, AJ, Zareba, W, et al. Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. J Cardiovasc Electrophysiol 2006; 17: 1161–1168.CrossRefGoogle ScholarPubMed
5. Tranebjaerg, L, Samson, RA, Green, GE. Jervell and Lange-Nielsen syndrome. In: Pagon RA, Bird TC, Dolan CR, Stephen K (eds). Gene Reviews. University of Washington, Seattle, WA, 2010, pp. 1–15.Google Scholar
6. Schwartz, PJ. Pharmacological and non-pharmacological management of the congenital long-QT syndrome: the rationale. Pharmacol Ther 2011; 131: 171–177.CrossRefGoogle ScholarPubMed
7. Garson, A Jr, Dick, M, Fournier, A, et al. The long-QT syndrome in children. An international study of 287 patients. Circulation 1993; 87: 1866–1872.Google Scholar
8. Roden, DM, Lazzara, R, Rosen, M, et al. Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. Circulation 1996; 94: 1996–2012.CrossRefGoogle ScholarPubMed
9. Dessertenne, F. Ventricular tachycardia with 2 variable opposing foci. Arch Mal Coeur Vaiss 1966; 59: 263–272.Google Scholar
10. Kleinman, CS, Glickstein, JS, Shaw, RF, et al. Echocardiography and Fetal Cardiology. Chapter 28. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF (eds). Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, 7th edn. Lippincott, Philadelphia, PA, 2008, pp. 592–617.Google Scholar
11. Tranebjaerg, L, Bathen, J, Tyson, J, Bitner-Glindzicz, M. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet (Semin Med Genet) 1999; 89: 137–146.Google Scholar
12. Goel, AK, Berger, S, Pelech, A, Dhala, A. Implantable cardioverter defribrillator therapy in children with long-QT syndrome. Pediatr Cardiol 2004; 25: 370–378.Google Scholar
13. Richter, S, Brugada, P. Risk-stratifying Jervell and Lange-Nielsen syndrome from clinical data. J. Cardiovasc Electrophysiol 2006; 17: 1169–1171.CrossRefGoogle ScholarPubMed
14. Neyroud, N, Tesson, F, Denjoy, I, et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nature Genet 1997; 15: 186–189.CrossRefGoogle ScholarPubMed
15. Tyson, J, Tranebjaerg, L, Bellman, S, et al. IsK and KVLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum Mol Genet 1997; 6: 2187–2193.CrossRefGoogle ScholarPubMed
16. Roden, DM, Spooner, PM. Inherited long QT syndromes: a paradigm for understanding arrythmogenesis. J Cardiovasc Eletrophysiol 1999; 10: 1664–1683.CrossRefGoogle Scholar
17. Huang, L, Bitner-Glindzicz, M, Tranebjaerg, L, Tinker, A. A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome. Cardiovasc Res 2001; 51: 670–680.CrossRefGoogle ScholarPubMed
18. Wangemann, P. Comparison of ion transport mechanisms between vestibular dark cells and strial marginal cells. Hear Res 1995; 90: 149–157.Google Scholar
19. Zdebik, AA, Wangemann, P, Jentsch, TJ. Potassium ion movement in the inner ear: insights from genetic disease and mouse models. Physiology 2009; 24: 307–316.Google Scholar
20. Goldenberg, I, Moss, AJ, Zareba, W. QT interval: how to measure it and what is “Normal”. J Cardiovas Electrophysiol 2006; 17: 333–336.Google Scholar
21. Priori, SG, Napolitano, C, Schwartz, PJ. Low penetrance in the long QT syndrome: clinical impact. Circulation 1999; 99: 529–533.Google Scholar
22. Schwartz, PJ, Moss, AJ, Vincent, GM, Crampton, RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88: 782–784.Google Scholar
23. Fraser, GR. Profound childhood deafness. J Med Genet 1964; 1: 118–151.Google Scholar
24. Fraser, GR, Froggatt, P, Murphy, T. Genetical aspects of the cardio-auditory syndrome of Jervell and Lange-Nielsen (congenital deafness and electrocardiographic abnormalities). Ann Hum Genet 1964; 28: 133–157.Google Scholar
25. James, TN. Congenital deafness and cardiac arrythmias. Am J Cardiol 1967; 19: 627–643.Google Scholar
26. Splawski, I, Timothy, KW, Vincent, GM, Atkinson, DL, Keating, MT. Molecular basis of the long-QT syndrome associated with deafness. N Eng J Med 1997; 336: 1562–1567.Google Scholar
27. Mathews, EC Jr, Blount, AW Jr, Townsend, JI. Q-T prolongation and ventricular arrhythmias, with and without deafness, in the same family. Am J Cardiol 1972; 29: 702–711.Google Scholar
28. van der Straaten, PJC, Bruins, CLD. A family with heritable electrocardiographic QT-prolongation. J Med Genet 1973; 10: 158–160.Google Scholar
29. Green, GE, Lehman, MH, Drescher, DG. Dominant inheritance of hearing impairment in patients with long QT syndrome. Am J Hum Genet 1995; 57: A91 (abstract).Google Scholar
30. Furlanello, F, Maccà, F, Dal Palù, C. Observation on a case of Jervell and Lange-Nielsen syndrome in an adult. Br Heart J 1972; 34: 648–652.Google Scholar
31. Crotti, L, Lundquist, AL, Insolia, R, et al. KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome. Circulation 2005; 112: 1251–1258.CrossRefGoogle ScholarPubMed
32. Zareba, W, Moss, AJ, Locati, EH, et al. Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol 2003; 42: 103–109.Google Scholar
33. Crotti, L, Spazzolini, C, Schwartz, PG, et al. The common long-QT syndrome mutation KCNQ1/A341V causes unusually severe clinical manifestations in patients with different ethnic backgrounds: toward a mutation-specific risk stratification. Circulation 2007; 116: 2366–2375.Google Scholar
34. Liu, JF, Goldenberg, I, Moss, AJ, et al. Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations. Ann Noninvasive Electrocardiol 2008; 13: 234–241.Google Scholar
35. Fugate, T II, Moss, AJ, Jons, C, et al. Long QT syndrome in African-Americans. Ann Noninvasive Electrocardiol 2010; 15: 73–76.Google Scholar
36. Mohammad-Panah, R, Demolombe, S, Neyroud, N, et al. Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias. Am J Hum Genet 1999; 64: 1015–1023.Google Scholar
37. Dorostokar, PC, Elder, M, Belhassen, B, Scheinman, MM. Long-term follow-up of patients with long QT syndrome treated with beta-blockers and continuous pacing. Circulation 1999; 100: 2431–2436.Google Scholar
38. Cooper, JM, Stephenson, EA, Berul, CI, Walsh, ED, Epstein, LM. Implantable cardioverter defibrillator lead complications and later extraction in children and young adults with congenital heart disease: implications for implantation and management. J Cardiovasc Electrophysiol 2003; 14: 344–349.CrossRefGoogle Scholar
39. DeMaso, DR, Lauretti, A, Spieth, L, et al. Psychological factors and quality of life in children and adolescents with implantable cardioverter defibrillaters. Am J Cardiol 2004; 93: 582–587.Google Scholar
40. Wolf, MJ, Zeltser, IJ, Salemo, J, et al. Electrical storm in children with an implantable cardioverter defibrillator: clinical features and outcome. Heart Rhythm 2007; 4 (Suppl): S43.Google Scholar
41. Stephenson, EA, Berul, CI. Electrophysiological interventions for inherited arrhythmia syndromes. Circulation 2007; 116: 1062–1080.CrossRefGoogle ScholarPubMed
42. Duggal, P, Vesely, MR, Wattanasirichaigoon, D, et al. Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Circulation 1998; 97: 142–146.Google Scholar
43. Sininger, YS, Cone-Wesson, B. Asymmetric cochlear processing mimics hemispheric specialization. Science 2004; 305: 1581.Google Scholar
44. Friedmann, I, Fraser, GR, Froggatt, P. Pathology of the ear in the cardio-auditory syndrome of Jervell and Lange-Nielsen (recessive deafness with electrocardiographic abnormalities). J Laryngol Otol 1966; 80: 451–470.Google Scholar
45. Vetter, DE, Mann, JR, Wangemann, P, et al. Inner ear defects induced by null mutation of the isk gene. Neuron 1996; 17: 1251–1264.Google Scholar
46. Rivas, A, Francis, HW. Inner ear abnormalities in a KCNQ1 (Kvlqt1) knockout mouse: a model of Jervell and Lange-Nielsen syndrome. Otol and Neurotol 2005; 26: 415–424.Google Scholar
47. Hone, SW, Smith, RJH. Understanding inner ear physiology at the molecular level. Adv Otorhinolaryngol 2002; 61: 1–20.Google Scholar
48. Kies, SJ, Pabelick, CM, Hurley, HA, White, RD, Ackerman, MJ. Anesthesia for patients with congenital long-QT syndrome. Anesthesiology 2005; 102: 204–210.Google Scholar
49. Adu-Gyamfi, Y, Said, A, Choudhary, UM, Abomelha, A, Sanyal, SK. Anesthetic-induced ventricular tachy-arrythmia in Jervell and Lange-Nielsen syndrome. Can J Anesth 1991; 38: 345–346.Google Scholar
50. Roden, DM. Taking the “Idio” out of “Idiosyncratic”: predicting Torsades de Pointes. Pace 1998; 21: 1029–1034.Google Scholar