Bristol Royal Hospital for Children, University Hospital Bristol, Bristol, UK.
Bristol Heart Institute, University Hospital Bristol, Bristol, UK.
Europace. 2018 Feb 1;20(2):377-385. doi: 10.1093/europace/euw433.
Timothy syndrome (TS) is an extremely rare multisystem disorder characterized by marked QT prolongation, syndactyly, seizures, behavioural abnormalities, immunodeficiency, and hypoglycaemia. The aim of this study was to categorize the phenotypes and examine the outcomes of patients with TS.
All patients diagnosed with TS in the United Kingdom over a 24-year period were reviewed. Fifteen centres in the British Congenital Arrhythmia Group network were contacted to partake in the study. Six patients with TS were identified over a 24-year period (4 boys and 2 girls). Five out of the six patients were confirmed to have a CACNA1C mutation (p.Gly406Arg) and the other patient was diagnosed clinically. Early presentation with heart block, due to QT prolongation was frequently seen. Four are still alive, two of these have a pacemaker and two have undergone defibrillator implantation. Five out of six patients have had a documented cardiac arrest with three occurring under general anaesthesia. Two patients suffered a cardiac arrest while in hospital and resuscitation was unsuccessful, despite immediate access to a defibrillator. Surviving patients seem to have mild developmental delay and learning difficulties.
Timothy syndrome is a rare disorder with a high attrition rate if undiagnosed. Perioperative cardiac arrests are common and not always amenable to resuscitation. Longer-term survival is possible, however, patients invariably require pacemaker or defibrillator implantation.
Timothy 综合征（TS）是一种极其罕见的多系统疾病，其特征为明显的 QT 延长、并指、癫痫发作、行为异常、免疫缺陷和低血糖。本研究的目的是对 TS 患者的表型进行分类并检查其结果。
回顾了英国 24 年来诊断为 TS 的所有患者。联系了英国先天性心律失常组网络中的 15 个中心参与研究。在 24 年期间发现了 6 例 TS 患者（4 名男孩和 2 名女孩）。6 例患者中有 5 例被证实存在 CACNA1C 突变（p.Gly406Arg），另 1 例患者经临床诊断。由于 QT 延长导致的早期出现的心脏传导阻滞是常见的。目前仍有 4 人存活，其中 2 人需要起搏器，2 人需要植入除颤器。6 例中有 5 例记录到心脏骤停，其中 3 例发生在全身麻醉下。2 例患者在住院期间发生心脏骤停，尽管立即使用除颤器，但复苏仍未成功。存活的患者似乎存在轻度发育迟缓和学习困难。
Timothy 综合征是一种罕见疾病，如果未被诊断则死亡率很高。围手术期心脏骤停很常见，并非总是可以复苏。虽然可能长期存活，但患者始终需要植入起搏器或除颤器。
