title: Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation.
abstract: BACKGROUND
  Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease). In an attempt to clarify the frontier between these two entities, we have characterized cardiac conduction defect and its evolution with aging in a cohort of 78 patients carrying a SCN5A mutation linked to Brugada syndrome.
  
  
  RESULTS
  Families were included in the study if a SCN5A mutation was identified in a BS proband and if at least two family members were mutation carriers. Sixteen families met the study criteria, representing 78 carriers. Resting ECG showed a spontaneous BS ECG pattern in 28 of 78 (36%) gene carriers. Intraventricular conduction anomalies were identified in 59 of 78 gene carriers including complete (17) or incomplete (24) right bundle branch block, right bundle branch block plus hemiblock (6), left bundle branch block (1), hemiblock (1), and parietal block (10). PR and QRS duration were longer in the gene carrier cohort in comparison with their relatives carrying no mutation. Finally, in the gene carrier cohort conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations.
  
  
  CONCLUSIONS
  The present study shows that the most common phenotype of gene carriers of a BS-type SCN5A mutation is progressive cardiac conduction defects similar to the Lenègre disease phenotype. In consequence, we propose that carriers of a SCN5A mutation need a clinical and ECG follow-up because of the risk associated with severe conduction defects.
authors.affiliation: L'Institut du thorax, Service de cardiologie, INSERM U533, Nantes, France. vincent.probst@chu-nantes.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Probst
authors.forename: Marie
authors.initials: M
authors.lastname: Allouis
authors.forename: Frederic
authors.initials: F
authors.lastname: Sacher
authors.forename: Sabine
authors.initials: S
authors.lastname: Pattier
authors.forename: Dominique
authors.initials: D
authors.lastname: Babuty
authors.forename: Philipe
authors.initials: P
authors.lastname: Mabo
authors.forename: Jacques
authors.initials: J
authors.lastname: Mansourati
authors.forename: Jacques
authors.initials: J
authors.lastname: Victor
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Schott
authors.forename: Pierre
authors.initials: P
authors.lastname: Boisseau
authors.forename: Denis
authors.initials: D
authors.lastname: Escande
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Marec
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D004562:Electrocardiography; D005192:Family Health; D005260:Female; D005602:France; D006327:Heart Block / Q000235:genetics* / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D015222:Sodium Channels