Pediatric Cardiology

, Volume 34, Issue 8, pp 2063–2067 | Cite as

Jervell and Lange–Nielsen Syndrome: Homozygous Missense Mutation of KCNQ1 in a Turkish Family

  • Ozlem Bostan
  • Şehime G. Temel
  • Hakan Cangül
  • Caroline N. S. Archer
  • Ergun Çil
Case Report

Abstract

Long QT syndrome is one of the most common cardiac ion channel diseases, but its morbidity and mortality rate can be lessened with an early diagnosis and proper treatment. This cardiac ventricular repolarization abnormality is characterized by a prolonged QT interval and a propensity for ventricular tachycardia (VT) of the torsades de pointes type. The long QT syndrome represents a high risk for presyncope, syncope, cardiac arrest, and sudden death. Jervell and Lange–Nielsen syndrome (JLNS) is a recessively inherited form of long QT syndrome characterized by profound sensorineural deafness and prolongation of the QT interval. Findings have shown that JLNS occurs due to homozygous and compound heterozygous pathogenic variants in KCNQ1 or KCNE1. A 3.5-year-old girl presented to the hospital with recurrent syncope, seizures, and congenital sensorineural deafness. Her electrocardiogram showed a markedly prolonged QT interval, and she had a diagnosis of JLNS. The sequence analysis of the proband showed the presence of a pathogenic homozygous missense variant (c.728G>A, p.Arg243His). Heterozygous mutations of KCNQ1 were identified in her mother, father, and sister, demonstrating true homozygosity. Even with high-dose beta-blocker therapy, the patient had two VT attacks, so an implantable cardioverter defibrillator was fitted. The authors suggest early genetic diagnosis for proper management of the disease in the proband and genetic counseling for both the proband and the girl’s extended family.

Keywords

Autosomal recessive long QT syndrome Deafness p.Arg243His 

References

  1. 1.
    Chouabe C, Neyroud N, Richard P, Denjoy I, Hainque B, Romey G et al (2000) Novel mutations in KvLQT1 that affect IKs activation through interactions with Isk. Cardiovasc Res 45:971–980CrossRefPubMedGoogle Scholar
  2. 2.
    Franqueza L, Lin M, Splawski I, Keating MT, Sanguinetti MC (1999) Long QT syndrome-associated mutations in the S4–S5 linker of.KvLQT1 potassium channels modify gating and interaction with minK subunits. J Biol Chem 274:21063–21070CrossRefPubMedGoogle Scholar
  3. 3.
    Goyal JP, Sethi A, Shah VB (2012) Jervell and Lange–Nielsen syndrome masquerading as intractable epilepsy. Ann Ind Acad Neurol 15:145–147CrossRefGoogle Scholar
  4. 4.
    Jervell A, Lange–Nielsen F (1957) Congenital deaf-mutism, functional heart disease with prolongation of Q–T interval and sudden death. Am Heart J 54:59–68CrossRefPubMedGoogle Scholar
  5. 5.
    Kannankeril PJ, Fish FA (2008) Disorders of cardiac rhythm and conduction. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF (eds) Moss and Adams’ heart disease in infants, children, and adolescents including the fetus and young adult, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 328–331Google Scholar
  6. 6.
    MacCormick JM, McAlister H, Crawford J, French JK, Crozier I, Shelling AN, Eddy C, Rees MI, Skinner JR (2009) Misdiagnosis of long QT syndrome as epilepsy at first presentation. Ann Emerg Med 54:26–32CrossRefPubMedGoogle Scholar
  7. 7.
    Mohammad-Panah R, Demolombe S, Neyroud N et al (1999) Mutations in dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias. Am J Hum Genet 64:1015–1023PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Park K, Piron J, Dahimene S, Me’rot J, Baro L, Escande D, Loussouarnet G (2005) Impaired KCNQ1–KCNE1 and phosphatidylinositol-4,5-bisphosphate interaction underlies the long QT syndrome. Circ Res 96:730–739CrossRefPubMedGoogle Scholar
  9. 9.
    Romano C (1965) Congenital cardiac arrythmia. Lancet I:658–659CrossRefGoogle Scholar
  10. 10.
    Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Toebin JA, Vincent MG, Keating MT (2000) Spectrum of mutations in long-QT syndrome genes KVLQT1, HERG, SCN5A, KCNE, and KCNE2. Circulation 102:1178–1185CrossRefPubMedGoogle Scholar
  11. 11.
    Tyson J, Tranebjaerg L, McEntagart M, Larsen LA, Christiansen M, Whiteford ML, Bathen J, Aslaksen B, Sørland SJ, Lund O, Pembrey ME, Malcolm S (2001) Mutational spectrum in the cardioauditory syndrome of Jervell-Lange & Nielsen syndrome. Erratum in Hum Genet 2001; 108:75. Hum Genet 107:499–503CrossRefGoogle Scholar
  12. 12.
    Ward OC (1964) A new familial cardiac syndrome in children. J Ir Med Assoc 54:103–106PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ozlem Bostan
    • 1
  • Şehime G. Temel
    • 2
    • 3
  • Hakan Cangül
    • 4
    • 5
  • Caroline N. S. Archer
    • 6
  • Ergun Çil
    • 1
  1. 1.Department of Paediatric CardiologyFaculty of Medicine, University of UludagBursaTurkey
  2. 2.Department of Medical GeneticsFaculty of Medicine, University of UludagBursaTurkey
  3. 3.Department of Histology and EmbryologyFaculty of Medicine, University of Near EastLefkosiaNorth Cyprus
  4. 4.Department of Medical and Molecular GeneticsClinical and Experimental Medical Faculty, University of BirminghamBirminghamUK
  5. 5.Department of Medical GeneticsFaculty of Medicine, University of BahcesehirİstanbulTurkey
  6. 6.Oxford Medical Genetics LaboratoriesCardiac Service, Oxford University Hospitals NHS Trust, The Churchill HospitalOxfordUK

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