儿童RYR2基因变异相关儿茶酚胺敏感性多形性室性心动过速诊治及随访分析

Clinical characteristics and follow-up of catecholaminergic polymorphic ventricular tachycardia associated with RYR2 gene variation in children

目的 探讨RYR2基因变异相关儿茶酚胺敏感性多形性室性心动过速(CPVT)的临床表现及治疗、随访情况。方法 回顾性分析2017年1月至2023年1月收治的CPVT患儿的临床资料,总结其治疗经过及随访结果。结果 共收治CPVT患儿6例,男4例、女2例,首发症状出现时平均年龄(3.5±0.5)岁。从首发症状到确诊的中位时间1.5(0.1~5.9)年。晕厥是最常见的临床表现,运动及情绪是主要诱因。6例患儿全外显子基因测序均为RYR2基因新发错义突变。在动态心电图中,小年龄患儿中房性心律失常及窦房结功能不全多见。4例患儿完成运动平板试验,2例患儿诱发双向室性期前收缩,2例诱发双向室性期前收缩及多形室性心动过速。基础治疗为口服普萘洛尔或美托洛尔,如仍有心律失常发生,辅助以氟卡尼或普罗帕酮口服;2例予以心脏永久起搏器治疗。平均随访时间(24.3±3.7)个月,所有患儿均存活,随访期间3例患儿偶有晕厥,1例间断心悸,2例无不适。结论 儿童RYR2基因变异相关CPVT临床表现多种多样,小年龄患儿中房性心律失常合并窦房结功能不全多见,药物治疗结合心脏起搏治疗效果理想。

Objective To investigate the clinical manifestations,treatment and follow-up of RYR2 gene variationrelated catecholaminergic polymorphic ventricular tachycardia(CPVT).Methods The clinical data of CPVT children admitted from January 2017 to January 2023 were retrospectively analyzed,and the course of treatment and follow-up results were summarized.Results A total of 6 children(4 boys and 2 girls)with CPVT were admitted,and the mean age of the patients was(3.5±0.5)years old when the first symptoms appeared.The median time from first symptom onset to diagnosis was 1.5(0.1-5.9)years.The most common clinical manifestation was syncope,with exercise and emotions being the main triggers.All 6 children had de novo missense mutations in the RYR2 gene identified through whole-exome sequencing.In dynamic electrocardiography,atrial arrhythmias and sinoatrial node dysfunction were commonly observed in younger children.Four patients underwent exercise stress testing,with 2 experiencing bidirectional ventricular premature contractions and 2 experiencing bidirectional ventricular premature contractions and polymorphic ventricular tachycardia.Initial treatment involved oral propranolol or metoprolol.If arrhythmias persisted,flecainide or propafenone was added as adjunctive therapy.Two patients received permanent cardiac pacemaker treatment(VVI).The mean follow-up time was(24.3±3.7)months,and all patients survived.During the follow-up period,3 children had occasional syncope,1 had intermittent palpitation,and 2 had no discomfort.Conclusions CPVT associated with RYR2 gene variations in children can present with various clinical manifestations.Atrial arrhythmias combined with sinoatrial node dysfunction are commonly observed in younger children.The combination of pharmacological therapy and cardiac pacemaker treatment yields favorable treatment outcomes.