Neuropediatrics
DOI: 10.1055/s-0040-1712488
Original Article

Next Generation Sequencing in Pediatric Epilepsy Using Customized Panels: Size Matters

Eva-Katharina Willimsky
1  Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Anna Munzig
2  Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany
,
Karin Mayer
2  Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany
,
Saskia Biskup
3  CeGaT GmbH, Tübingen, Germany
,
Angela Abicht
4  Medical Genetics Center—MGZ, Munich, Germany
,
Konstanze Hoertnagel
2  Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany
,
Hubertus von Voss
2  Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany
,
Hanns-Georg Klein
2  Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany
,
Imma Rost
2  Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany
,
Line H.G. Larsen
5  Amplexa Genetics, Odense, Denmark
,
Hanns Atli Dahl
5  Amplexa Genetics, Odense, Denmark
,
Hannes Hoelz
1  Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Celina von Stuelpnagel
1  Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
6  Paracelsus Medical University, Salzburg, Austria
,
Ingo Borggraefe
1  Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
7  Comprehensive Epilepsy Center (Pediatric section), Ludwig-Maximilians University of Munich, Munich, Germany
› Author Affiliations

Abstract

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.



Publication History

Received: 09 February 2020

Accepted: 07 April 2020

Publication Date:
21 October 2020 (online)

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