Next-generation Sequencing Findings and Clinical Correlations in Children with Unknown Causes of Epilepsy at a Tertiary Care Pediatric Hospital in Thailand
Keywords:
Genetic, Epilepsy, Children, Next-generation sequencing (NGS)Abstract
Background: Next-generation sequencing (NGS) has become an increasingly important technique for identifying the unknown causes of pediatric epilepsy. NGS increased the diagnostic yield by at least 30-40% in children with epilepsy, but these data in Thai children is still limited. This study aimed to determine the diagnostic yield and factors associated with the detection of disease-causing genes by NGS in children with unknown causes of epilepsy in Thailand. Methods: A single-center retrospective study of 42 children with unknown causes of epilepsy who had available NGS results for the diagnosis of genetic epilepsy from Jan 1st, 2015 to June 30th, 2021, was conducted at Queen Sirikit National Institute of Child Health, Thailand. Patients with identified causes of epilepsy were excluded. Gene variants were classified based on their pathogenicity, and related clinical factors were determined. Results: Of the 42 unexplained causes of epilepsy with available results from their NGS tests, 50% had a disease-causing gene detected and were identified as genetically causing epilepsy. Among these 21 patients with NGS-identified genetic epilepsy, 57.1% were female, 33.3% had a family history of epilepsy, 4.8% had a history of consanguinity, and all of them were developmentally delayed. The most common identified disease-causing gene was SCN1A (38.1%). The factor significantly associated with the detection of disease-causing genes was Dravet phenotype (p-value = .004), and other clinical parameters were not significant factors. Furthermore, the change in patient management after available NGS results was significantly greater in patients with NGS-identified genetic epilepsy than in those without NGS-identified genetic epilepsy (61.9% vs. 4.8%, p < .001). Conclusions: Genetic testing should be advised for finding disease-causing genes in children with undiscovered causes of epilepsy since genetic abnormalities were discovered by NGS in 50% of children with unknown causes of epilepsy, and the clinical care for these patients may change.
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