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.