Background： The patients with early-onset epileptic encephalopathy （EOEE） suffer from neurodevelopmental delay. The aim of this study was to analyze the clinical manifestations and amplitude-integrated encephalogr...Background： The patients with early-onset epileptic encephalopathy （EOEE） suffer from neurodevelopmental delay. The aim of this study was to analyze the clinical manifestations and amplitude-integrated encephalogram （aEEG） characteristics of infants with EOEE with onset within the neonatal period, to make early diagnosis to improve the prognosis. Methods： One-hundred and twenty-eight patients with neonatal seizure were enrolled and followed up till 1 year old. Sixty-six neonates evolved into EOEE were as the EOEE group, the other 62 were as the non-EOEE （nEOEE） group. Then we compared the clinical and aEEG characteristics between the two groups to analyze the manifestations in neonates with EOEE. Results： Compared to the nEOEE group, the incidence of daily seizure attacks, more than two types of convulsions, more than two antiepileptic drugs （AEDs） application, severely abnormal aEEG background, absence of cyclicity, and more than two seizures detection were significantly higher in the EOEE group （P 〈 0.05） （97% vs. 54.8%; 30.3% vs. 14.5%; 97.0% vs. 25.4%; 39.4% vs. 3.2%; 57.6% vs. 9.7%; and 56% vs. 3.2%, respectively）. Severely abnormal background pattern （odds ratio [OR] = 0.081, 95% confidence interval [CI]：0.009-0.729, P = 0.025） and more than two seizures detection by aEEG （OR = 0.158, 95% CI： 0.043-0.576, P = 0.005） were the independent risk factors for the evolvement into EOEE. The upper and lower margins of active sleep （AS） and quiet sleep （QS） were significantly higher in EOEE group than those of the control group （P 〈 0.05） （34.3 ± 13.6 vs. 21.3 ± 6.4; 9.9 ± 3.7 vs. 6.7 ± 2.2; 41.2 ± 15.1 vs. 30.4 ± 11.4;and 11.9 ± 4.4 vs. 9.4 ± 4.0; unit： μV, respectively）. AS upper margin was demonstrated a higher diagnostic specificity and sensitivity for EOEE than another three parameters according to the receiver operating characteristic curves; the area under the curve was 0.827. Conclusions： The clinical characteristics of the neonatal seizure which will evolve into EOEE were more than two AEDs application, high seizure frequency （daily attack）, and more than two types of the seizure. Significant high voltage, severely abnormal background, absence of cyclicity, and more than two seizures detected on aEEG were the meaningful indicators to the prediction of EOEE.展开更多
目的 探讨细胞周期蛋白依赖性蛋白激酶5(cyclin-dependent kinase-like 5,CDKL5)基因新发突变导致患儿早发性癫痫脑病的临床特征及分子遗传学特点。方法 收集西北妇女儿童医院儿童神经内科确诊的2例早发性癫痫脑病患儿的临床资料,应用...目的 探讨细胞周期蛋白依赖性蛋白激酶5(cyclin-dependent kinase-like 5,CDKL5)基因新发突变导致患儿早发性癫痫脑病的临床特征及分子遗传学特点。方法 收集西北妇女儿童医院儿童神经内科确诊的2例早发性癫痫脑病患儿的临床资料,应用二代测序技术对核心家系成员进行全外显子测序分析,并用Sanger测序法进行突变验证。结果例1患儿出生后20天出现强直阵挛、不典型痉挛形式的癫痫发作,两种抗癫痫药物联合治疗后效果较好;例2患儿出生后1个月出现全面性强直阵挛发作,并伴显著的上下肢屈曲抖动,进展为难治性痉挛发作及严重精神发育迟滞和语言运动发育障碍,多种抗癫痫药物及生酮饮食联合治疗效果差。两例患儿全基因组基因拷贝数变异(copy number variations,CNVs)检测未见明确致病变异。核心家系全外显子组测序结果发现,例1患儿CDKL5基因第12外显子上存在一杂合新发无义突变:NM_003159.2:c.1307C>G(p.Ser436^(*)),其父母该位点未见异常;例2患儿该基因第13外显子存在c.1974_1975del(p.Val659GlyfsTer23)新发杂合移码突变,其父母该位点未见异常。根据2015年美国医学遗传学与基因组学学会(the American College of Medical Genetics and Genomics,ACMG)指南,以上变异均为致病突变。结论CDKL5基因c.1307C>G无义突变和c.1974_1975del移码突变是先证者早发性癫痫脑病遗传学病因的新发致病变异,扩充了致病基因CDKL5的基因变异谱。展开更多
文摘Background： The patients with early-onset epileptic encephalopathy （EOEE） suffer from neurodevelopmental delay. The aim of this study was to analyze the clinical manifestations and amplitude-integrated encephalogram （aEEG） characteristics of infants with EOEE with onset within the neonatal period, to make early diagnosis to improve the prognosis. Methods： One-hundred and twenty-eight patients with neonatal seizure were enrolled and followed up till 1 year old. Sixty-six neonates evolved into EOEE were as the EOEE group, the other 62 were as the non-EOEE （nEOEE） group. Then we compared the clinical and aEEG characteristics between the two groups to analyze the manifestations in neonates with EOEE. Results： Compared to the nEOEE group, the incidence of daily seizure attacks, more than two types of convulsions, more than two antiepileptic drugs （AEDs） application, severely abnormal aEEG background, absence of cyclicity, and more than two seizures detection were significantly higher in the EOEE group （P 〈 0.05） （97% vs. 54.8%; 30.3% vs. 14.5%; 97.0% vs. 25.4%; 39.4% vs. 3.2%; 57.6% vs. 9.7%; and 56% vs. 3.2%, respectively）. Severely abnormal background pattern （odds ratio [OR] = 0.081, 95% confidence interval [CI]：0.009-0.729, P = 0.025） and more than two seizures detection by aEEG （OR = 0.158, 95% CI： 0.043-0.576, P = 0.005） were the independent risk factors for the evolvement into EOEE. The upper and lower margins of active sleep （AS） and quiet sleep （QS） were significantly higher in EOEE group than those of the control group （P 〈 0.05） （34.3 ± 13.6 vs. 21.3 ± 6.4; 9.9 ± 3.7 vs. 6.7 ± 2.2; 41.2 ± 15.1 vs. 30.4 ± 11.4;and 11.9 ± 4.4 vs. 9.4 ± 4.0; unit： μV, respectively）. AS upper margin was demonstrated a higher diagnostic specificity and sensitivity for EOEE than another three parameters according to the receiver operating characteristic curves; the area under the curve was 0.827. Conclusions： The clinical characteristics of the neonatal seizure which will evolve into EOEE were more than two AEDs application, high seizure frequency （daily attack）, and more than two types of the seizure. Significant high voltage, severely abnormal background, absence of cyclicity, and more than two seizures detected on aEEG were the meaningful indicators to the prediction of EOEE.
文摘目的 探讨细胞周期蛋白依赖性蛋白激酶5(cyclin-dependent kinase-like 5,CDKL5)基因新发突变导致患儿早发性癫痫脑病的临床特征及分子遗传学特点。方法 收集西北妇女儿童医院儿童神经内科确诊的2例早发性癫痫脑病患儿的临床资料,应用二代测序技术对核心家系成员进行全外显子测序分析,并用Sanger测序法进行突变验证。结果例1患儿出生后20天出现强直阵挛、不典型痉挛形式的癫痫发作,两种抗癫痫药物联合治疗后效果较好;例2患儿出生后1个月出现全面性强直阵挛发作,并伴显著的上下肢屈曲抖动,进展为难治性痉挛发作及严重精神发育迟滞和语言运动发育障碍,多种抗癫痫药物及生酮饮食联合治疗效果差。两例患儿全基因组基因拷贝数变异(copy number variations,CNVs)检测未见明确致病变异。核心家系全外显子组测序结果发现,例1患儿CDKL5基因第12外显子上存在一杂合新发无义突变:NM_003159.2:c.1307C>G(p.Ser436^(*)),其父母该位点未见异常;例2患儿该基因第13外显子存在c.1974_1975del(p.Val659GlyfsTer23)新发杂合移码突变,其父母该位点未见异常。根据2015年美国医学遗传学与基因组学学会(the American College of Medical Genetics and Genomics,ACMG)指南,以上变异均为致病突变。结论CDKL5基因c.1307C>G无义突变和c.1974_1975del移码突变是先证者早发性癫痫脑病遗传学病因的新发致病变异,扩充了致病基因CDKL5的基因变异谱。
