Probst Vincent, Allouis Marie, Sacher Frederic, Pattier Sabine, Babuty Dominique, Mabo Philipe, Mansourati Jacques, Victor Jacques, Nguyen Jean-Michel, Schott Jean-Jacques, Boisseau Pierre, Escande Denis, Le Marec Hervé
L'Institut du thorax, Service de cardiologie, INSERM U533, Nantes, France.
J Cardiovasc Electrophysiol. 2006 Mar;17(3):270-5. doi: 10.1111/j.1540-8167.2006.00349.x.
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.
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.
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.
编码心脏钠通道的SCN5A基因功能丧失性突变可导致 Brugada 综合征（BS）以及进行性心脏传导疾病（遗传性 Lenègre 病）。为了明确这两种疾病之间的界限，我们对 78 例携带与 Brugada 综合征相关的 SCN5A 突变的患者队列进行了心脏传导缺陷及其随年龄变化情况的特征分析。
如果在 BS 先证者中鉴定出 SCN5A 突变，且至少有两名家庭成员为突变携带者，则将这些家庭纳入研究。16 个家庭符合研究标准，共 78 名携带者。静息心电图显示，78 名基因携带者中有 28 名（36%）呈现出 Brugada 综合征自发心电图模式。78 名基因携带者中有 59 名存在室内传导异常，包括完全性（17 例）或不完全性（24 例）右束支传导阻滞、右束支传导阻滞合并半阻滞（6 例）、左束支传导阻滞（1 例）、半阻滞（1 例）和壁内阻滞（10 例）。与未携带突变的亲属相比，基因携带者队列中的 PR 和 QRS 间期更长。最后，在基因携带者队列中，传导缺陷随年龄增长逐渐加重，有 5 例最终需要植入起搏器。
本研究表明，BS 型 SCN5A 突变基因携带者最常见的表型是类似于 Lenègre 病表型的进行性心脏传导缺陷。因此，我们建议 SCN5A 突变携带者需要进行临床和心电图随访，因为存在严重传导缺陷相关风险。
