Zhao N, Cheng M M, Yang Y, Niu X Y, Chen Y, Yang X L, Zhang Y H
Department of Pediatrics, Peking University First Hospital, Bejing 100034, China.
Zhonghua Er Ke Za Zhi. 2022 Nov 2;60(11):1140-1146. doi: 10.3760/cma.j.cn112140-20220609-00527.
To summarize the genetics and clinical phenotypes of epilepsy children with 2q24.3 microdeletion. All the patients with 2q24.3 microdeletion were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2017 to July 2022. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed. There were 13 patients with 2q24.3 microdeletion were included. All 13 patients had de novo copy number variation (CNV) with a deletion size ranged 0.18-7.31 Mb. The main pathogenic genes in the region were SCN3A, SCN2A, TTC21B, SCN1A and SCN9A genes Among the 13 patients, 7 were boys, and 6 were girls. The onset age of epilepsy was 3.3(2.5, 6.0) months. Multiple seizure types were observed, including focal seizures in 13 patients, generalized tonic-clonic seizures (GTCS) in 6 patients, myoclonic seizures in 3 patients, epileptic spasm in 2 patients, and tonic seizures in 2 patients. Seizures were fever sensitivity in 9 patients. Status epilepticus was observed in 6 patients. One case had normal mental motor development and 12 cases had different degrees of developmental delay. Six patients had craniofacial abnormality, 1 had six-finger deformity of the right thumb, and 1 had multiple system abnormalities. EEG showed focal discharge in 3 cases, multifocal discharges in 5 cases, multifocal and generalized discharges in 1 case. Brain magnetic resonance imaging (MRI) showed enlargement of subarachnoid spaces in the frontal and temporal region in 4 patients, enlargement of lateral ventricle in 4 patients and delayed myelination of white matter in 1 patient. Dravet syndrome was diagnosed in 5 cases. The age at the last follow-up were 2.5(1.4,5.5) years, 1 patient was seizure free longer than 1 year, and 12 patients still had seizures. The epilepsy associated with 2q24.3 microdeletion is mainly induced by the deletion of SCN3A, SCN2A and SCN1A genes. The seizure onset age of 2q24.3 microdeletion related epilepsy was in infancy. Multiple seizure types are observed and the common seizure types include focal seizures and GTCS. Most patients have fever sensitivity and status epilepticus. Most patients have developmental delay. The phenotype of patients with deletion of SCN3A and SCN2A gene is more severe than that of patients with deletion of SCN1A gene only.
总结2q24.3微缺失癫痫患儿的遗传学及临床表型。回顾性收集2017年3月至2022年7月在北京大学第一医院儿科就诊的所有2q24.3微缺失患者。分析其临床表现、脑电图（EEG）及神经影像学特征。共纳入13例2q24.3微缺失患者。所有13例患者均为新发拷贝数变异（CNV），缺失大小为0.18 - 7.31 Mb。该区域主要致病基因为SCN3A、SCN2A、TTC21B、SCN1A和SCN9A基因。13例患者中，男7例，女6例。癫痫起病年龄为3.3（2.5，6.0）个月。观察到多种发作类型，其中13例患者有局灶性发作，6例有全身强直 - 阵挛发作（GTCS），3例有肌阵挛发作，2例有癫痫性痉挛，2例有强直发作。9例患者发作对热敏感。6例患者出现癫痫持续状态。1例患者精神运动发育正常，12例有不同程度发育迟缓。6例患者有颅面畸形，1例右拇指多指畸形，1例有多系统异常。EEG显示3例局灶性放电，5例多灶性放电，1例多灶性及全身性放电。脑磁共振成像（MRI）显示4例患者额颞区蛛网膜下腔增宽，4例患者侧脑室扩大，1例患者白质髓鞘化延迟。5例诊断为Dravet综合征。末次随访年龄为2.5（1.4，5.5）岁，1例患者无癫痫发作超过1年，12例患者仍有发作。2q24.3微缺失相关癫痫主要由SCN3A、SCN2A和SCN1A基因缺失所致。2q24.3微缺失相关癫痫起病年龄在婴儿期。观察到多种发作类型，常见发作类型包括局灶性发作和GTCS。多数患者发作对热敏感且有癫痫持续状态。多数患者有发育迟缓。SCN3A和SCN2A基因缺失患者的表型比仅SCN1A基因缺失患者更严重。
