Evaluation of SCN1A gene mutation in children with febrile convulsion

Introduction and Aim: Febrile convulsions are the most common cause of childhood convulsions. Febrile seizures, generally benign, may exhibit a recurrence feature in some cases and, albeit rarely, carry the risk of developing epileptic seizures, maintaining its importance and relevance. Although the exact causes of febrile convulsions are not fully known, studies have shown the significant role of genetic predisposition. A large portion of the literature on febrile convulsions focuses on risk factors, hereditary characteristics, epilepsy development, and recurrence risk. Therefore, during routine evaluations, careful consideration of family history and pedigree analysis may not only help determine whether a patient with febrile convulsions is at risk of developing epilepsy in the future but also contribute to the diagnosis, treatment, and prognosis decisions. The aim of this study is to investigate the significance of the association between febrile convulsions and SCN1A gene mutation by detecting SCN1A gene mutation in children with febrile convulsions and healthy individuals who have not experienced febrile convulsions. Identifying patients with relevant gene mutations in children with febrile convulsions and performing genetic screening in those who have never experienced them may provide an opportunity to determine the likelihood of experiencing and recurring febrile convulsions and take necessary precautions in advance. Material-Methods: Thirty-six pediatric patients aged 6 months to 5 years who experienced febrile convulsions or had previously experienced them and presented to the Pediatric Clinics and Pediatric Emergency Clinic of Zonguldak Bülent Ecevit University Faculty of Medicine Training and Research Hospital between November 2018 and November 2021 were included in the study. As a control group, 34 adult patients without febrile convulsion history, neurological symptoms, or any other accompanying diseases were selected from the community. Blood samples for genetic analysis were collected in 1 tube containing EDTA from the patients. SCN1A gene analysis was performed on the blood samples at the INTERGEN Genetic and Rare Diseases Diagnosis Research and Application Center. Findings: The mean age at the first febrile convulsion episode in the study group of 36 patients ranged from 10 months to 57 months, with a mean age of 22.3±11.55 months. The majority of the study group (69.4%) were male. Ten patients (27.8%) had a family history of febrile convulsions, and two patients (5.6%) had a family history of epilepsy. There was no consanguinity history in the parents of the patients. The mean fever at the onset of the first febrile convulsion episode was 38.35±0.61°C. Twenty-five patients (69.4%) had simple febrile convulsions, ten patients (27.8%) had complex febrile convulsions, and one patient (2.8%) had febrile status. The recurrence rate of febrile convulsions in our study was 33.3%. The mean duration of seizures was 2.97±4.12 minutes, with a minimum of 1 minute and a maximum of 20 minutes. Seven patients (19.4%) had a history of antiepileptic drug administration during seizures, and 100% of those who received antiepileptic drugs experienced recurrence. A statistically significant relationship was found between the administration of antiepileptic drugs during seizures and recurrence (p=0.040). SCN1A mutation was detected in only one patient (2.7%) in the study. Recurrence was not observed in this patient. The genetic analysis resulted in a likely pathogenic change c.3734G>A (p.R1245Q) (p.Arg1245Gln) (Heterozygous) in this patient. Additionally, rs2298771 Heterozygous polymorphism (benign) was detected. Regarding SCN1A rs2298771 polymorphism, no changes were detected in 8 out of 36 patients with febrile convulsions (22.2%), an additional heterozygous polymorphism was observed in 1 patient (2.8%), homozygous polymorphism was found in 11 patients (30.6%), heterozygous polymorphism was observed in 14 patients (38.9%), and two patients (5.6%) had heterozygous benign changes in addition to homozygous polymorphism. No pathogenic mutations were detected in the control group, and no changes were observed in 26 out of 34 individuals (76.4%). Different polymorphism types were detected in 5 patients (14.7%), and heterozygous polymorphism was observed in 2 patients (5.8%) and homozygous polymorphism in 1 patient (2.9%) in the control group. While polymorphism was detected in 77.8% of patients with febrile convulsions, it was observed in only 10.7% of the control group. A statistically significant difference was found between the groups in terms of SCN1A rs2298771 polymorphism (p<0.001). When the clinical effect of SCN1A polymorphism was evaluated in the patient group, no statistically significant relationship was found with gender, age at the first febrile convulsion, fever degree during febrile convulsion, seizure type, family history of febrile convulsions, family history of epilepsy, pediatric neurology referral, and antiepileptic drug use (respectively, p=0.214; p=0.955; p=0.813; p=0.388; p=0.397; p=0.400, p=0.388, p=1). Conclusion: We concluded that rs2298771 polymorphism may predispose to febrile convulsions genetically. However, due to the multifactorial etiopathogenesis of febrile convulsions, the limited number of patients in our study, its location in a local region, and the inability of some families to accurately recall certain information about the time of febrile convulsions, further studies with larger patient groups are needed to determine how the findings obtained will contribute to the prognosis and treatment of febrile convulsions. Although most FSs resolve spontaneously, identifying the genetic predisposition to recurring FSs with poor prognosis, febrile status epilepticus, or the development of epileptic syndromes following infantile FSs represents an important future goal for researchers. Our study will shed light on new studies on the genetic transmission, risk factors, and treatment of FSs. Keywords: Febrile Convulsion, SCN1A gene, rs2298771, Polymorphism