Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant...

The purposes of this study were three-fold: (i) to determine the contribution of known genes to the causation of a broad-spectrum of pediatric drug-resistant epilepsy (DRE), (ii) to compare the diagnostic yield and cost among different next-generation sequencing (NGS) approaches, and especially (iii) to assess how NGS approaches can benefit patients by improving diagnosis and treatment efficiency.

This study enrolled 273 pediatric DRE patients with no obvious acquired etiology. Seventy-four patients underwent whole-exome sequencing (WES), 141 patients had epilepsy-related gene panel testing, and another 58 patients had clinical WES gene panel testing. We obtained these patients' seizure and hospitalization frequency by periodic follow-up phone calls and outpatient visits.

Genetic diagnosis was achieved in 86 patients (31.5%) and involved 93 likely disease-causing mutations in 33 genes. In this study, the detection rates of the epilepsy-related gene panel, the clinical WES gene panel, and WES were 32.6% (46/141), 44.8% (26/58), and 17.3% (13/74), respectively. Moreover, 34 patients accepted corrective therapy according to their mutant genes, after which 52.9% (18/34) became seizure-free and 38.2% (13/34) achieved seizure reduction. In the end, patients with either positive or negative genetic results had significantly fewer hospitalization incidents (times/half year) than before (positive genetic results group 0.58 ± 1.14 vs 0.10 ± 0.26; negative genetic results group 0.72 ± 1.65 vs 0.12 ± 0.33).

These results offer further proof that NGS approaches represent powerful tools for establishing a definitive diagnosis. Moreover, this study indicated how NGS can improve treatment efficacy and reduce hospitalization in children with DRE.