Abstract 19725: Prevalence and Clinical Phenotype of Sodium and Calcium Channel Mutations in Brugada Syndrome
In approximately 20% of patients with the Brugada phenotype mutations in the SCN5A gene are found. Recently, mutations in CACNB2b and CACNA1c encoding the cardiac calcium channel (ICa) have been described causing the Brugada phenotype. In a large single centre population of genotyped patients with Brugada syndrome (BS) we present the prevalence, the clinical and electrocardiographic phenotype of sodium and calcium channel mutations.
Patients and Methods: Consecutive patients with the clinical diagnosis of BS were genotyped with respect to mutations in SCN5A, CACNB2b and CACNA1c. Clinical and electrocardiographic parameters were compared with respect to sodium and calcium channel mutations.
Results: Within 91 patients (mean age 38±15 years; 52 males) diagnosed with Brugada syndrome a positive genotype was found in 48 patients (53%). Thirty-six patients (40%) had mutations in the SCN5A gene, 9 (10%) in CACNB2b and 3 (3%) in CACNA1c. Among the 58 probands in this cohort, sixteen (28%) presented with a positive genotype. Clinical parameters were not significantly different between sodium and calcium channel mutation carriers. A spontaneous type 1 ST ECG was observed in 30% patients with SCN5A mutations and 29 % with calcium channel mutations. Patients with sodium channel mutations have significantly longer PR intervals (195±26 ms vs. 143±27 ms; p<0.0001). Calcium channel mutation carriers exhibit shorter QTc intervals (370±21ms vs. 420±40ms; p<0.0001).
Conclusions: Extending genetic screening to CACNB2b and CACNA1c increases the yield of genotyping in patients with Brugada syndrome to approximately 30% in index patients. Mutations in genes encoding the cardiac calcium channel account for approximately 25 % of all positive genotypes identified in this cohort. A higher proportion of positive genotypes in BS may facilitate diagnosis and risk stratification. Electrocardiographically, patients with SCN5A mutations exhibit longer PR and QTc intervals compared to calcium channel mutation carriers. 12 lead ECG may help differentiating between sodium and calcium channel mutation carriers.
- © 2010 by American Heart Association, Inc.