[Homozygotous mutation of the SCN5A gene responsible for congenital long QT syndrome with 2/1 atrioventricular block]

Arch Mal Coeur Vaiss. 2002 May;95(5):440-6.
[Article in French]

Abstract

Long QT syndrome is characterized by a prolongation of the QT interval on the surface ECG. This clinically and genetically heterogeneous cardiac disease is potentially lethal due to ventricular polymorphic tachyarrhythmias leading to syncope or sudden death. It is transmitted according to different mendelian modes due to mutations in several genes coding for cardiac ion channels. Heterozygous mutations in KCNQ1, HERG, SCN5A, KCNE1 and KCNE2 genes are responsible for the dominant form without deafness whereas homozygous mutations in KCNQ1 and KCNE1 are responsible for the recessive form (Jervell and Lange-Nielsen syndrome) associated with congenital deafness. We report the case of a 5 year-old boy referred for syncope with a prolongation of the QTc interval (526 ms) and a 2/1 Atrio-Ventricular (AVB) block on the surface ECG. Under beta-blocking therapy, the sinus rate decreased and the 2/1 AVB disappeared. Electrophysiological study evidenced an infra-hisian block and a unipolar ventricular endocardial pacemaker was implanted. A V1777M missense mutation was identified in the C-terminal part of SCN5A, cardiac sodium channel gene, at the homozygous state in the proband and at the heterozygous state in both parents and 2 sibblings. Only the proband had a severe phenotype with syncope and AV conduction anomalies. All other genetically affected subjects were asymptomatic. This study provides evidence for the involvement of homozygous LQT3 forms in "functional" AVB.

Publication types

  • Case Reports
  • English Abstract

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • Electrocardiography
  • Humans
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / therapy
  • Male
  • Molecular Sequence Data
  • NAV1.5 Voltage-Gated Sodium Channel
  • Pacemaker, Artificial
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Prognosis
  • Sodium Channels / genetics*
  • Syncope

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels