ABSTRACT
Background & Objective: SCN1A gene which encodes for sodium channel alpha 1 subunit has been found to be the most common mutated gene in patients with epilepsy. This study aims to characterize the SCN1A mutations as well as to describe genotype and phenotype association in children with SCN1Arelated infantile-onset epileptic encephalopathies in Malaysia. Methods: Children with infantile-onset epileptic encephalopathy mostly suspected to have Dravet syndrome who had mutational analysis for SCN1A gene from hospitals all over Malaysia were included in the study. Their epilepsy syndrome diagnosis was classified into severe myoclonic epilepsy in infancy and its variants. Polymerase chain reaction and bidirectional sequencing were used to identify SCN1A mutations. Results: A total of 38 children with heterozygous mutations were analysed, 22 (57.9%) of which were novel mutations. Truncated mutations were the most common mutation type (19, 50%). Other mutation types were missense mutations (14, 36.8%), splice site mutations (4, 10.5%) and in-frame deletion (1, 2.6%). The mean age of seizure onset was 4.7 months. Seizure following vaccination was observed in 26.3% of the children. All of them had drug resistant epilepsy. There was no significant association between the type of mutation with the syndromic diagnosis, age of seizure onset, tendency of the seizures to cluster or having status epilepticus, mean age when developmental delay was observed and response to various antiepileptic drugs. Conclusion: This study expands the spectrum of SCN1A mutations and proves the importance of SCN1A gene testing in diagnosing infantile-onset epileptic encephalopathies patients. Although, our study does not support any clinically meaningful genotype-phenotype association for SCN1A-related infantile-onset epileptic encephalopathies, the clinical characteristics of our cohort are similar to those that have been described in previous studies.