Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder
Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder
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DOI：
10.1212/wnl.0000000000003352
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发表时间：
2016-11-22
期刊：
影响因子：
9.9
通讯作者：
Leonard, Helen
中科院分区：
文献类型：
--
作者：
Fehr, Stephanie;Wong, Kingsley;Leonard, Helen
目的：探讨癫痫发作的结果及其与基因型和功能能力的个体与细胞周期蛋白依赖性激酶样5（CDKL 5）disorder.Methods：使用国际CDKL 5疾病数据库，我们确定了172例致病性CDKL 5突变。我们根据预测的结构和功能结果将单个突变分为4组。负二项回归模型之间的线性关联，目前的癫痫发作率和突变组，目前的援助水平需要走10步，和表达沟通的最高水平，用于传达拒绝或request.Results：所有，但3（169/172）患者有癫痫病史。癫痫发作时的中位年龄为6周（范围1周至1.5岁），确定时的中位癫痫发作率为每天2次（范围0-20次）。在校正了行走能力和混杂因素（包括使用或其他多种治疗）后，与无功能蛋白的患者相比，aa 172和aa 781之间截短突变的患者癫痫发作率较低（发生率比[IRR] 0.57; 95%置信区间[CI] 0.35-0.93）。与调整基因型后能力最差的患者相比，行走能力和使用口语能力与当前癫痫发作率较低相关（行走：IRR 0.62; 95% CI 0.39-0.99，交流：IRR 0.48; 95% CI 0.23-1.02）。在中位年龄在5年的问卷调查完成，那些以前用皮质类固醇治疗过的癫痫发作比那些从未接受过治疗，是否有婴儿痉挛症的历史。结论：癫痫是普遍的，但不是强制性的CDKL 5障碍。基因型和功能能力与癫痫发作频率有关，这似乎是抗癫痫药物难治的。
Objective: To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder.Methods: Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences. Negative binomial regression was used to model the linear association between current seizure rate and mutation group, current level of assistance required to walk 10 steps, and the highest level of expressive communication used to convey refusal or request.Results: All but 3 (169/172) patients had a history of epilepsy. The median age at seizure onset was 6 weeks (range 1 week-1.5 years) and the median seizure rate at ascertainment was 2 per day (range 0-20 per day). After adjusting for walking ability and confounders including use or otherwise of polytherapy, seizure rate was lower in those with truncating mutations between aa172 and aa781 compared to those with no functional protein (incidence rate ratio [IRR] 0.57; 95% confidence interval [CI] 0.35-0.93). Ability to walk and use of spoken language were associated with lower rates of current seizures when compared to those with the least ability after adjusting for genotype (walking: IRR 0.62; 95% CI 0.39-0.99, communication: IRR 0.48; 95% CI 0.23-1.02). At a median age at questionnaire completion of 5 years, those previously treated with corticosteroids had more frequent seizures than those who have never been treated, whether or not there was a history of infantile spasms.Conclusions: Epilepsy is pervasive but not mandatory for the CDKL5 disorder. Genotype and functional abilities were related to seizure frequency, which appears refractory to antiepileptic drugs.