Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype
Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype
复制标题
DOI：
10.1002/ajmg.a.38191
复制
发表时间：
2017-06-01
影响因子：
2
通讯作者：
Naidu, Sakkubai R.
中科院分区：
文献类型：
--
作者：
Crosson, Jane;Srivastava, Siddharth;Naidu, Sakkubai R.
Rett综合征（RTT）是由MECP 2突变引起的，导致各种神经系统症状。还报告了校正QT间期（QTc）延长，这是RTT中猝死的推测原因。本研究的目的是将RTT患者的QTc与年龄、临床严重程度和基因型相关。作为我们前瞻性自然史研究的一部分，100例MECP 2突变的RTT患者（98例女性，2例男性）接受了基线神经学评价（KKI-RTT严重程度量表）和QTc测量（标准12导联心电图）。队列的平均QTc为422.6 msec，未超过年龄的正常值。7/100例患者（7%）出现QTc延长（>450 msec）。QTc有随年龄和临床严重程度增加而增加的趋势（P = 0.09）。无R106 C、R106 W、R133 C、R168*、R270*、R294*、R306 C、R306 H和R306 P突变患者出现QTc延长。R255* 突变（2/8，25%）和大缺失（1/4，25%）患者中QTc延长的比例相对较高。QTc间期延长的总体存在与突变类别无关（P = 0.52）。我们的研究结果表明，在RTT，QTc延长的患病率低于以前的报告。因此，所有RTT患者都需要进行基线ECG;如果QTc延长，则需要进行心脏随访。如果初始QTc正常，则可能不需要每年进行一次ECG检查，尤其是年轻患者。然而，需要更大的样本量来巩固QTc与年龄和临床严重程度之间的关联。轻度QTc延长超过正常数据的生物学和临床意义尚未确定。
Rett syndrome (RTT) is caused by MECP2 mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) is also reported and is a speculated cause of sudden death in RTT. The purpose of this study was to correlate QTc in RTT patients with age, clinical severity, and genotype. 100 RTT patients (98 females, 2 males) with MECP2 mutations underwent baseline neurological evaluation (KKI-RTT Severity Scale) and QTc measurement (standard 12 lead electrocardiogram) as part of our prospective natural history study. Mean QTc of the cohort was 422.6 msec, which did not exceed the normal values for age. 7/100 patients (7%) had QTc prolongation (>450 msec). There was a trend for increasing QTc with age and clinical severity (P = 0.09). No patients with R106C, R106W, R133C, R168*, R270*, R294*, R306C, R306H, and R306P mutations demonstrated QTc prolongation. There was a relatively high proportion of QTc prolongation in patients with R255* mutations (2/8, 25%) and large deletions (1/4, 25%). The overall presence of QTc prolongation did not correlate with mutation category (P = 0.52). Our findings demonstrate that in RTT, the prevalence of QTc prolongation is lower than previously reported. Hence, all RTT patients warrant baseline ECG; if QTc is prolonged, then cardiac followup is warranted. If initial QTc is normal, then annual ECGs, particularly in younger patients, may not be necessary. However, larger sample sizes are needed to solidify the association between QTc and age and clinical severity. The biological and clinical significance of mild QTc prolongation above the normative data remains undetermined.