Phenotypic and genetic characteristics of 24 cases of early infantile epileptic encephalopathy in East China, including a rare case of biallelic UGDH mutations

Abstract Background Early infantile epileptic encephalopathy (EIEE) is a group of highly heterogeneous diseases, both phenotypically and genetically. Usually, it starts early on and manifests as intractable epilepsy, abnormal electroencephalogram, and growth retardation/intellectual impairment. With the advent of next‐generation sequencing (NGS), its genetic etiology has attracted increasing clinical attention. This study aimed to investigate the genetic characteristics and clinical phenotypes of patients with EIEE from a central hospital in Eastern China. Methods This study retrospectively included the gene variants from 24 EIEE‐positive patients admitted between January 2021 and January 2022 to a hospital in Anhui Province, China. The genetic diagnosis was performed in all cases by trio‐based whole‐exome sequencing (WES). Additionally, Video electroencephalogram (VEEG) and neuroimaging examinations were performed. Results A total of 24 children were included. The average age at the first seizure was approximately 5 months. About 42% of children had developmental retardation of varying degrees, 43% had brain structural abnormalities, and 64% had VEEG abnormalities. In addition, other phenotypes, including endocrine metabolism and cardiac structural abnormalities, have been independently reported. In total, fifteen pathogenic gene variants were identified in 24 patients. The main pathogenic genes identified were SCN1A (25%, 6/24), KCNQ2 (8.3%, 2/24), and TBC1D24 (8.3%, 2/24). We also found an extremely rare case of EIEE84 type caused by biallelic UGDH gene variants, predicting that this variant might affect the stability of the protein structure. Conclusions SCN1A pathogenic variants are the main factor leading to EIEE, similar to previously published cohort reports. NGS is useful for accurate clinical diagnoses and precise treatment choices. We also reported a rare case of EIEE84 caused by variants in the UGDH gene in a Chinese patient. This study further enriches the known spectrum of pathogenic EIEE genes.