Extending the KCNQ2 encephalopathy spectrum Clinical and neuroimaging findings in 17 patients
Extending the KCNQ2 encephalopathy spectrum Clinical and neuroimaging findings in 17 patients
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DOI：
10.1212/01.wnl.0000435296.72400.a1
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发表时间：
2013-11-05
期刊：
影响因子：
9.9
通讯作者：
De Jonghe, Peter
中科院分区：
文献类型：
--
作者：
Weckhuysen, Sarah;Ivanovic, Vanja;De Jonghe, Peter
目的：目的探讨KCNQ 2基因突变在新生儿癫痫性脑病（NEE）中的发生频率，扩大KCNQ 2癫痫性脑病的表型谱。方法：采用经典桑格测序法对84例不明原因NEE患者进行KCNQ 2基因突变筛查。收集了另外6例通过基因组检测到KCNQ 2突变的患者的临床数据。详细的表型进行了特别注意癫痫发作频率，认知结果，和video-EGE.Results：在队列中，我们确定了9个不同的杂合子从头KCNQ 2错义突变11 84例（13%）。通过基因组检测到的6个错义突变中有2个是复发性的，并且存在于该队列的患者中。发作时的癫痫发作通常包括强直性姿势，通常伴有局灶性阵挛性抽搐，并伴有呼吸暂停伴饱和度下降。1例经基因诊断的患者在5个月大时癫痫发作。根据发作时的癫痫发作频率和认知结果，我们划定了3个临床亚组，将KCNQ 2脑病的范围扩大到中度智力残疾和/或发作时癫痫发作不频繁的患者。重复突变导致相对同质的表型。1例患者对瑞替加滨反应良好; 5例患者对卡马西平反应良好。在6例患者中，记录到癫痫发作伴心动过缓。结论：KCNQ 2基因突变导致约13%的不明原因的NEE。患者表现出广泛的严重程度，虽然罕见，但婴儿癫痫发作是可能的。
Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy.Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG.Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy.Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.