Factors influencing neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy: a follow-up study of 21 cases / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.