Tian X J, Wang X H, Ding C H, Fang F, Dai L F, Deng J, Wang H M
Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Zhonghua Er Ke Za Zhi. 2022 Mar 2;60(3):232-236. doi: 10.3760/cma.j.cn112140-20210817-00681.
To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.
分析儿童GRIN2B基因相关神经发育障碍的临床及基因特征。回顾性收集2016年11月至2021年2月首都医科大学附属北京儿童医院、国家儿童医学中心神经内科11例GRIN2B基因相关神经发育障碍患儿的资料，总结其临床特征、脑电图（EEG）、脑影像学及基因检测结果。11例患儿中，男6例，女5例。其中2例诊断为发育性癫痫性脑病，癫痫发作起病年龄分别为3个月和9个月，发作类型包括癫痫性痉挛、强直发作、强直痉挛和局灶性发作，1例患儿还伴有惊吓发作。EEG显示发作间期多灶性癫痫样放电，2例均加用2种以上抗癫痫药物，部分有效但无法控制，存在中度至重度智力及运动发育迟缓。9例患儿的表型为发育迟缓或智力残疾无癫痫发作，就诊年龄1岁至6岁4个月，其中5例为重度发育迟缓，2例为中度，2例为轻度发育迟缓。3例观察到多灶性癫痫样放电，3例未发现异常，其余3例未行EEG检查。10例患儿行脑磁共振成像（MRI）检查，6例有非特异性异常，4例正常。通过二代测序在这11例患者中检测到9个GRIN2B基因杂合变异，8例为错义变异，1例为无义变异，均为……且其中3个为新变异。10例患者发现错义变异，其中6例为重度发育迟缓，3例为中度，1例为轻度发育迟缓，但无义变异患者表现为轻度发育迟缓无癫痫发作。儿童GRIN2B基因相关神经发育障碍的表型多样，从无癫痫发作的轻度智力损害到重度癫痫性脑病。癫痫表型患者通常起病于婴儿期，痉挛和局灶性发作是最常见的发作类型，且癫痫发作难治。大多数错义变异患者有重度发育迟缓。
