Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy
Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy
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DOI：
10.1212/01.wnl.0000335760.02995.ca
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发表时间：
2009-01-20
期刊：
影响因子：
9.9
通讯作者：
Ackerman, M. J.
中科院分区：
文献类型：
--
作者：
Johnson, J. N.;Hofman, N.;Ackerman, M. J.
背景：长QT综合征（LQTS）通常表现为晕厥、癫痫发作或猝死。LQTS患者常被误诊为癫痫发作或癫痫，并接受抗癫痫药物治疗。该基因名为KCNH2，负责2型LQTS (LQT2)，最初是从海马中克隆出来的，编码海马星形胶质细胞中活跃的钾通道。我们试图验证“癫痫表型”更常归因于LQT2患者的假设。方法：回顾了1998年至2006年在两个大型LQTS转诊中心进行LQTS临床评估和基因检测的343例连续无关联患者（232例女性，诊断时平均年龄27 +/- 18岁，QTc 471 +/- 57 msec）的图表。阳性癫痫表型被定义为存在个人或家族癫痫发作史或AED治疗史。结果：98/343（29%）先证者有癫痫表型。发作表型在LQT2（36/ 77,47 %）比LQT1 （16/ 72,22 %, p < 0.002）和LQT3 （7/ 28,25 %, p < 0.05， NS）更常见。LQT1和LQT3联合队列与预期的背景发作表型发生率没有显著差异。个人癫痫发作史在LQT2中更为常见（30/ 77,39%），高于其他LQTS亚型（11/ 106,10%,p < 0.001）。结论：在LQT2患者中，癫痫诊断和抗癫痫药物治疗更为常见。就像在其他lqts易感基因（如KCNQ1/耳聋和SCN5A/胃肠道症状）中观察到的非心脏器官表型一样，这种新的lqt2 -癫痫关联提出了lqt2引起的kcnh2编码钾通道的扰动可能导致复发性癫痫发作活动的易感性。神经病学(R) 2009；72:224 - 231
Background: Long QT syndrome (LQTS) typically presents with syncope, seizures, or sudden death. Patients with LQTS have been misdiagnosed with a seizure disorder or epilepsy and treated with antiepileptic drug (AED) medication. The gene, KCNH2, responsible for type 2 LQTS (LQT2), was cloned originally from the hippocampus and encodes a potassium channel active in hippocampal astrocytes. We sought to test the hypothesis that a "seizure phenotype" was ascribed more commonly to patients with LQT2.Methods: Charts were reviewed for 343 consecutive, unrelated patients ( 232 females, average age at diagnosis 27 +/- 18 years, QTc 471 +/- 57 msec) clinically evaluated and genetically tested for LQTS from 1998 to 2006 at two large LQTS referral centers. A positive seizure phenotype was defined as the presence of either a personal or family history of seizures or history of AED therapy.Results: A seizure phenotype was recorded in 98/343 (29%) probands. A seizure phenotype was more common in LQT2 (36/77, 47%) than LQT1 (16/72, 22%, p < 0.002) and LQT3 (7/28, 25%, p < 0.05, NS). LQT1 and LQT3 combined cohorts did not differ significantly from expected, background rates of a seizure phenotype. A personal history of seizures was more common in LQT2 (30/77, 39%) than all other subtypes of LQTS (11/106, 10%, p < 0.001).Conclusions: A diagnostic consideration of epilepsy and treatment with antiepileptic drug medications was more common in patients with LQT2. Like noncardiac organ phenotypes observed in other LQTS-susceptibility genes such as KCNQ1/deafness and SCN5A/gastrointestinal symptoms, this novel LQT2-epilepsy association raises the possibility that LQT2-causing perturbations in the KCNH2-encoded potassium channel may confer susceptibility for recurrent seizure activity. Neurology (R) 2009;72:224-231