Genetic mutations in febrile sensitivity epilepsy correlate with earlier onset and specific diagnoses in children.

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Frontiers in Medicine Published April 14, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Note that gene-positive epilepsy cases show earlier onset and specific diagnoses compared to gene-negative controls in this cohort.

This retrospective cohort study evaluated children with abnormal genetic testing related to febrile sensitivity epilepsy at Wuxi Children's Hospital. The population included 30 gene-positive cases and 30 gene-positive and 31 gene-negative cases. The primary focus was on clinical features, molecular genetic characteristics, and the relationship between genotype, clinical phenotype, and treatment efficacy. Secondary outcomes included onset age, developmental delay, ACMG classification, mutation type, and final diagnosis.

Regarding main results, the onset of epilepsy occurred early within one year after birth in 20 of the 30 gene-positive cases. Developmental delay was present in 17 of the 30 cases. The final diagnosis distribution among gene-positive cases included 11 (36.7%) with Dravet syndrome, 4 (13.3%) with PCDH19-related epilepsy, 4 (13.3%) with generalized epilepsy with febrile seizures plus, 1 (3.3%) with epilepsy with myoclonic-atonic seizures, 2 (6.7%) with focal epilepsy, and 8 (26.7%) with other types. Comparisons between positive and negative groups showed that patients in the positive group had a significantly earlier age at onset (p < 0.05). Differences between effective and ineffective groups were noted regarding ACMG classification, mutation type, and onset age group (≤1 year), with p < 0.05.

Safety and tolerability data were not reported in this study. Key limitations include the lack of reported follow-up duration and the absence of data on treatment efficacy relationships. The study does not establish causality between specific mutations and outcomes due to the observational design. Practice relevance is limited by the single-center setting and the small sample size of gene-positive cases.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

ObjectiveTo 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.MethodsThis 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.ResultsAmong 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 SCN1A gene (13 cases), PCDH19 (4 cases), ADGRV1 (3 cases), and CACNB4 (2 cases) as well as one case each of mutations in SCN2A, PRRT2, CACNA1A, CACNA1E, CACNA1H, KCNA2, CHD2, and KIAA2022, 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 PCDH19-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) (p  0.05). Comparison between the positive and negative groups revealed that patients in the positive group had a significantly earlier age at onset (p

Genetic mutations in febrile sensitivity epilepsy correlate with earlier onset and specific diagnoses in children.

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Genetic mutations in febrile sensitivity epilepsy correlate with earlier onset and specific diagnoses in children.

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