Mutacje genetyczne i objawy kliniczne u 30 dzieci z padaczką związaną z wrażliwością na gorączkę

OBJECTIVE: To explore the clinical features and molecular genetic characteristics of epilepsy related to fever sensitivity caused by various types of gene mutations, and to analyze the relationships of genotype and clinical phenotype with clinical treatment efficacy. METHODS: This retrospective study was conducted on 30 cases of children with abnormal genetic testing related to febrile sensitivity epilepsy treated in Wuxi Children's Hospital between June 2016 and April 2023. All 61 children who met the inclusion criteria underwent whole exome sequencing (WES); clinical features were compared between the 30 gene-positive patients and the 31 gene-negative patients. Genetic testing results and clinical data of the 30 positive cases were summarized and the children were divided into "effective" and "ineffective" groups according to the efficacy of clinical treatment for comparisons. RESULTS: Among the 30 gene-positive children, the onset of epilepsy occurred early, with 20 cases occurring within 1 year after birth, and 17 cases having developmental delay. Thirty cases of pathogenic genes related to epilepsy were detected with mutations in the gene (13 cases), (4 cases), (3 cases), and (2 cases) as well as one case each of mutations in , , , , , , , and , which was identified as a novel gene mutation related to epilepsy. The final diagnosis was 11 cases (36.7%) of Dravet syndrome, four cases (13.3%) of -related epilepsy, four cases (13.3%) of generalized epilepsy with febrile seizures plus, one case (3.3%) of Epilepsy with myoclonic-atonic seizures, two cases (6.7%) of focal epilepsy, and eight cases (26.7%) of other types of epilepsy. There were differences between the 'effective' and 'ineffective' groups in the different pathogenic levels of American College of Medical Genetics and Genomics (ACMG) classification, mutation type (gene) and the onset age group (≤1 year group) ( < 0.05), while there were no differences in sex, presence or absence of status epilepticus, and ion channel efficacy ( > 0.05). Comparison between the positive and negative groups revealed that patients in the positive group had a significantly earlier age at onset ( < 0.05), a higher frequency of status epilepticus ( < 0.05), and a higher rate of developmental delay after onset ( < 0.001). CONCLUSION: Febrile sensitivity-related epilepsy in children is primarily caused by , , and mutations, manifesting mainly as Dravet syndrome and PCDH19-related epilepsy. The novel mutation expands the gene spectrum of this condition. Early age at onset, status epilepticus, and developmental delay are clinical red flags for genetic etiology, supporting early genetic testing in infants ≤1 year to guide precision treatment.