At present, the proportion of DRUG-RESISTANT epilepsy (DRE) in children is still maintained at about 30%, and it is often combined with mental retardation, affecting the quality of life, so the diagnosis and treatment of DRE is still a major challenge in neurology.

Analyze the genetic and clinical characteristics of DRE in children to provide a theoretical basis for clinical genetic testing.

A retrospective analysis of 95 children with DRE who were hospitalized in Hebei Children's Hospital from 2020 to 2022. According to the genetic test results, they were divided into gene mutation positive group (44 cases) and gene mutation negative group (51 cases). Collected general information (including gender, age of onset, medication use, history of febrile convulsions, family history of epilepsy, etc.), clinical features (seizure types, epilepsy syndromes, developmental conditions), and ancillary examinations [genetic testing, video electroencephalography (VEEG) examination, neuroimaging] from the children, and analyse the genetic aetiology and clinical features of DRE.

Of the 95 children with DRE, 55 (57.9%) were male and 40 (42.1%) were female, with a median age of onset of 1.00 (0.50, 4.00) years and number of medications used of 3 (2, 4) ; the age of onset of the children in the mutation-positive group was younger than that in the mutation-negative group (Z=-5.322, P=0.001) ; comparing the gender of the children, history of febrile seizures, family history of epilepsy, and number of medications used in the two groups, the differences were not statistically significant (P>0.05). Epileptic syndromes were diagnosed in 38 (40.0%) of the children, of which 76.3% (29/38) had onset in the neonatal or infantile period; the percentage of epileptic syndromes was higher in the mutation-positive group than in the mutation-negative group (χ²=12.065, P=0.001). Clinical seizure types were diverse, with 2 or more seizure types being the most common, accounting for 52.6% (50/95), followed by a single focal seizure, accounting for 33.7% (32/95) ; there was no statistically significant difference in the comparison of seizure types between the two groups of children with DRE (χ²=2.920, P=0.404). Developmental screening was improved in 57 children, of whom 43 (75.4%) showed varying degrees of developmental delay after the onset of the disease, and 33 (76.7%) showed generalised developmental delay; the percentage of children with developmental delay in the mutation-positive group was higher than that in the mutation-negative group (χ²=5.728, P=0.017). Genetic variations were detected in 44 cases, resulting in a positive detection rate of 46.3%, predominantly involving ion channel-related mutations, with SCN1A being the most prevalent single-gene mutation. Ninety (94.7%) children had abnormal VEEG examinations, with focal epileptic discharges predominating; the percentage of peak dysrhythmias was higher in the mutation-positive group than in the mutation-negative group (χ²=7.425, P=0.006). Structural etiology was present in 25 (26.3%) children, including 12 in the mutation-positive group and 13 in the mutation-negative group; the difference in the structural etiology of the children with DRE was not statistically significant when comparing the two groups (χ²=0.039, P=0.844) .

Genetic factors are an important etiological factor for DRE in children. The young age of onset and developmental delay suggests that it is related to a genetic etiology, and genetic testing should be actively improved at an early stage, which can help in the early diagnosis of DRE and precise treatment.

目前儿童药物难治性癫痫（DRE）在儿童癫痫中的占比维持在30%左右，且常合并精神发育迟滞，影响患儿生活质量，因此DRE的诊疗仍然是神经病学的重大挑战。

分析儿童DRE的遗传学特点及临床特征，为临床进行基因检测提供理论依据。

回顾性选取2020—2022年于河北省儿童医院住院治疗且完善基因检测的95例DRE患儿为研究对象，根据基因检测结果分为基因突变阳性组（44例）和基因突变阴性组（51例）。收集患儿的一般资料（包括性别、发病年龄、用药情况、发热惊厥史、癫痫家族史等）、临床特征（发作类型、癫痫综合征、发育情况）、辅助检查[基因检测、视频脑电图（VEEG）检查、神经影像学检查]，分析DRE的遗传病因及临床特征。

95例DRE患儿中，男55例（57.9%）、女40例（42.1%），中位发病年龄为1.00（0.50，4.00）岁，用药数量为3（2，4）种；基因突变阳性组患儿发病年龄小于基因突变阴性组（Z=-5.322，P=0.001）；两组患儿性别、发热惊厥史、癫痫家族史、用药数量比较，差异均无统计学意义（P>0.05）。38例（40.0%）的患儿确诊为癫痫综合征，其中76.3%（29/38）在新生儿或婴儿期发病；基因突变阳性组患儿癫痫综合征占比高于基因突变阴性组（χ²=12.065，P=0.001）。临床发作类型多样，最常见的为2种及以上发作类型，占52.6%（50/95），其次为单一局灶性发作，占33.7%（32/95）；两组DRE患儿发作类型比较，差异无统计学意义（χ²=2.920，P=0.404）。57例患儿完善了发育筛查，其中43例（75.4%）在发病后出现不同程度的发育迟缓，33例（76.7%）表现为全面性发育迟缓；基因突变阳性组患儿发育迟缓占比高于基因突变阴性组（χ²=5.728，P=0.017）。44例患儿检出变异基因，阳性检出率为46.3%，其中以离子通道类变异为主，SCN1A为最常见的单基因突变。90例（94.7%）患儿VEEG检查异常，以局灶性癫痫放电为主；基因突变阳性组患儿高峰失律占比高于基因突变阴性组（χ²=7.425，P=0.006）。25例（26.3%）患儿存在结构性病因，其中基因突变阳性组12例，基因突变阴性组13例；两组DRE患儿结构性病因比较，差异无统计学意义（χ²=0.039，P=0.844）。

遗传因素为儿童DRE的重要病因，提示发病年龄小、发育迟缓与遗传性病因有关，应积极早期完善基因检测，有助于早期诊断DRE并精准治疗。