Next Generation Sequencing in Pediatric Epilepsy Using Customized Panels: Size Matters
Introduction Next generation sequencing (NGS) with customized gene panels is a helpful tool to identify monogenic epilepsy syndromes. The number of genes tested within a customized panel may vary greatly. The aim of the present study was to compare the diagnostic yield of small (<25 kb) and large (>25 kb) customized epilepsy panels.
Methods This retrospective cohort study investigated data of 190 patients of 18 years or younger, with the diagnosis of an epilepsy of unknown etiology who underwent NGS using customized gene panels. Small (<25 kb) and large (>25 kb) panels were compared regarding the distribution of benign/likely benign and pathogenic/likely pathogenic variants and variants of unclear significance. In addition, differences of the diagnostic yield with respect to epilepsy severity, i.e., developmental and epileptic encephalopathy [DEE] vs. non-DEE, were analyzed.
Results The diagnostic yield defined as pathogenic or likely pathogenic variants in large panels was significantly increased (29% [n = 14/48] vs. 13% [n = 18/142], p = 0.0198) compared with smaller panels. In non-DEE patients the increase of the diagnostic yield in large panels was significant(35% n = 6/17 vs. 13% n = 12/94, p = 0.0378), which was not true for DEE patients.
Discussion This study indicates that large panels are superior for pediatric patients with epilepsy forms without encephalopathy (non-DEE). For patients suffering from DEE small panels of a maximum of 10 genes seem to be sufficient. The proportion of unclear findings increases with rising panel sizes.
Conclusion Customized epilepsy panels of >25 kb compared with smaller panels show a significant higher diagnostic yield in patients with epilepsy especially in non-DEE patients.
Keywordsnext generation sequencing - NGS panel - pediatric epilepsy - customized panel - panel size - yield
Received: 09 February 2020
Accepted: 07 April 2020
21 October 2020 (online)
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Stuttgart · New York
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