Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.
Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.
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DOI：
10.1186/1750-1172-8-80
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发表时间：
2013-05-22
影响因子：
3.7
通讯作者：
Villard L
中科院分区：
文献类型：
--
作者：
Milh M;Boutry-Kryza N;Sutera-Sardo J;Mignot C;Auvin S;Lacoste C;Villeneuve N;Roubertie A;Heron B;Carneiro M;Kaminska A;Altuzarra C;Blanchard G;Ville D;Barthez MA;Heron D;Gras D;Afenjar A;Dorison N;Doummar D;Billette de Villemeur T;An I;Jacquette A;Charles P;Perrier J;Isidor B;Vercueil L;Chabrol B;Badens C;Lesca G;Villard L
早发性癫痫性脑病（EOEE）是一种严重的异质性疾病，其中病因学、癫痫发作和/或发作间期EEG对神经发育有负面影响。几种基因与EOEE相关，分子诊断检查具有挑战性，因为相似的表型与不同基因的突变相关，并且因为一个给定基因的突变可能与非常不同的表型相关。最近，在约10%的EOEE患者中发现了KCNQ 2的新生突变。我们的目的是确认KCNQ 2是一个重要的基因，包括在诊断检查EOEEs，并充分描述突变患者的临床和EEG特征。我们在71例EOEE患者中筛选了KCNQ 2，没有任何脑结构异常。要纳入队列，患者的癫痫应在3个月龄前开始，并伴有异常发作间期EEG和神经功能缺损。脑部MRI不应显示任何可能导致癫痫的结构异常。在这71名患者中，16名患者（23%）在KCNQ 2中发生了新生突变。有趣的是，在大多数病例中，这些患者的初始癫痫特征与先前在良性家族性新生儿癫痫（BFNE）病例中描述的那些特征相当，BFNE也由KCNQ 2突变引起。然而，与BFNE相反，发作间期背景EEG发生改变，并显示多灶性尖峰或抑制-爆发模式。持续的癫痫和发展变化很大，但总体上很严重：15/16例患者有明显的认知障碍，一半的患者没有癫痫，5/16例患者在3岁之前可以行走，只有2/16例患者获得了说话的能力。这项研究证实，KCNQ 2经常在新生儿癫痫性脑病中发生突变。我们在这里表明，尽管病情的开始相对刻板，但神经和癫痫的演变是可变的。
Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found in about 10% of EOEE patients. Our objective was to confirm that KCNQ2 was an important gene to include in the diagnosis workup of EOEEs and to fully describe the clinical and EEG features of mutated patients. We have screened KCNQ2 in a cohort of 71 patients with an EOEE, without any brain structural abnormality. To be included in the cohort, patient’s epilepsy should begin before three months of age and be associated with abnormal interictal EEG and neurological impairment. Brain MRI should not show any structural abnormality that could account for the epilepsy. Out of those 71 patients, 16 had a de novo mutation in KCNQ2 (23%). Interestingly, in the majority of the cases, the initial epileptic features of these patients were comparable to those previously described in the case of benign familial neonatal epilepsy (BFNE) also caused by KCNQ2 mutations. However, in contrast to BFNE, the interictal background EEG was altered and displayed multifocal spikes or a suppression-burst pattern. The ongoing epilepsy and development were highly variable but overall severe: 15/16 had obvious cognitive impairment, half of the patients became seizure-free, 5/16 could walk before the age of 3 and only 2/16 patient acquired the ability to speak. This study confirms that KCNQ2 is frequently mutated de novo in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the neurological and epileptic evolution is variable.
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影响因子：
11.2
作者：
Weckhuysen, Sarah;Mandelstam, Simone;de Jonghe, Peter
通讯作者：
de Jonghe, Peter
影响因子：
30.8
作者：
Charlier, C;Singh, NA;Leppert, M
通讯作者：
Leppert, M
影响因子：
56.9
作者：
Biervert, C;Schroeder, BC;Steinlein, OK
通讯作者：
Steinlein, OK
影响因子：
2.2
作者：
Dedek, K;Fusco, L;Steinlein, OK
通讯作者：
Steinlein, OK
DOI：
10.1073/pnas.1216867110
发表时间：
2013-03-12
影响因子：
11.1
作者：
Miceli, Francesco;Soldovieri, Maria Virginia;Taglialatela, Maurizio
通讯作者：
Taglialatela, Maurizio