Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation.
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.
Probst
Vincent
V
L'Institut du thorax, Service de cardiologie, INSERM U533, Nantes, France. vincent.probst@chu-nantes.fr
Allouis
Marie
M
Sacher
Frederic
F
Pattier
Sabine
S
Babuty
Dominique
D
Mabo
Philipe
P
Mansourati
Jacques
J
Victor
Jacques
J
Nguyen
Jean-Michel
JM
Schott
Jean-Jacques
JJ
Boisseau
Pierre
P
Escande
Denis
D
Le Marec
Hervé
H
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
D015222:Sodium Channels