Analysis of pathogenic genes and phenotypic characteristics of 81 children with epilepsy and movement disorders

Objective To summarize the pathogenic gene mutation spectrum and related phenotypic characteristics in children with epilepsy accompanied by movement disorders (E-MD). Methods Retrospective analysis was conducted on 81 children with genetically confirmed E-MD who were treated in Department of Pediatrics, the Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2024. Clinical data, including pathogenic gene mutations, clinical manifestations, electroencephalography (EEG) findings, and neuroimaging characteristics, were collected and analyzed. Results Whole-exome sequencing of the 81 E-MD patients revealed 45 pathogenic genes. The mutations mainly involved genes related to action potential formation, synaptic transmission, and cellular function, including 15 ion channel–related genes, 9 genes associated with cellular function, 7 enzyme-related genes, 6 synaptic-related genes, and 4 transcription-related genes. The age of seizure onset ranged from 2 days to 14 years. Seizure types included generalized tonic-clonic seizures (54 cases), febrile seizures (28 cases), spasms (18 cases), myoclonic seizures (17 cases), tonic seizures (2 cases), and atonic seizures (1 case). Focal seizures occurred in 31 patients, and multiple seizure types were observed in 53 patients. EEG findings showed background slowing in 8 cases, focal epileptiform discharges in 47 cases, and generalized or multifocal discharges in 28 cases, including 8 with hypsarrhythmia and 7 with burst-suppression patterns; 2 patients had normal EEGs. Cranial imaging abnormalities were detected in 28 children (34.6%). Conclusions E-MD presents with heterogeneous clinical manifestations and is associated with a broad spectrum of gene mutations, among which ion channel–related variants are the most common. Abnormalities in synaptic transmission, transcription regulation, cellular metabolism, enzymatic modulation, and cell–cell interactions may also contribute to the shared pathophysiological mechanisms underlying E-MD.