Next‐generation sequencing in pediatric‐onset epilepsies: Analysis with target panels and personalized therapeutic approach

作者：Barbara Castellotti, Francesca Ragona, Elena Freri, Giuliana Messina, Stefania Magri, Roberto Previtali, Roberta Solazzi, Silvana Franceschetti, Franco Taroni, Laura Canafoglia, Cinzia Gellera, Tiziana Granata, Jacopo C. DiFrancesco · 发表于：Epilepsia Open · 年份：2024 · DOI：10.1002/epi4.13039 · 被引用次数：12 · 研究领域：Genomics and Rare Diseases、Glycogen Storage Diseases and Myoclonus、Epilepsy research and treatment

OBJECTIVE: The objective of this study is to report the results of the genetic analysis in a large and well-characterized population with pediatric-onset epilepsies and to identify those who could benefit from precision medicine treatments. METHODS: In this retrospective observational study, we consecutively recruited patients with pediatric-onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in-depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next-generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy. RESULTS: We detected likely pathogenic or pathogenic variants (classes IV and V) in 24% of the 562 patients who underwent genetic investigations. By the evaluation of patients' data, we observed that some features (onset of epilepsy before one year old, presence of neurological deficits, psychomotor delay/cognitive disability, and malformative aspects at brain MRI) were significantly associated with class IV or V variants. Moreover, statistical analysis showed that the diagnostic yield resulted higher for patients affected by Progressive Myoclonic Epilepsy (PME) and with early onset developmental and epileptic encephalopathies (DEE), compared with focal epilepsies, genetic generalized epilepsies, DEE with onset at/after 1 y.o., a...