Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death early diagnosis of asymptomatic carriers - Early diagnosis of asymptomatic carriers
Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death early diagnosis of asymptomatic carriers - Early diagnosis of asymptomatic carriers
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DOI：
10.1016/s0735-1097(02)01946-0
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发表时间：
2002-07-17
影响因子：
24
通讯作者：
Nava, A
中科院分区：
文献类型：
--
作者：
Bauce, B;Rampazzo, A;Nava, A
目的探讨RyR2基因突变在努力诱导性多形性室性心律失常(PVA)、晕厥和青少年猝死家系中的作用。背景RyR2基因突变与PVA、晕厥和因身体或情绪应激引起的猝死有关。所有受试者均接受了RyR2基因突变筛查、心电图、24小时动态心电图、信号平均心电图、二维超声心动图和运动负荷试验。结果在8个家系中发现6种不同的RyR2基因突变。有43名家庭成员携带这种基因突变。在这些患者中，28人(65%)表现出努力诱发的心律失常症状或体征，1人在随访期间突然死亡。家族史显示有19例青少年在努力或情绪激动时猝死。在具有相同突变的两个家系中，没有受试者在压力测试中出现PVA；因此，猝死和晕厥是唯一的临床表现。除两名受试者外，所有受试者的12导联心电图均正常，而5名患者的SACG显示出阳性的晚期电位。在43例受试者中，17例(39.5%)二维超声心动图显示右室局部运动异常和轻度结构改变。结论1/3以上的RyR2基因突变携带者在负荷试验中无症状和PVA，EP研究缺乏PVA诱导性，基因筛查对无症状携带者的早期诊断和猝死的预防具有重要意义。
Objectives We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death.Background The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress.Methods We studied 81 subjects (39 males and 42 females; mean age 31+/-20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients.Results Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA.Conclusions The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.