title: Diagnostic Yield of Epilepsy Panels in Children With Medication-Refractory Epilepsy.
abstract: When no chromosomal variations are identified, patients with suspected genetic etiologies can be tested using next-generation sequencing utilizing epilepsy panels. The primary objective of this study was to analyze the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects with non-clinically significant comparative genomic hybridization microarray results.
  
  
  
  We completed a single-center retrospective review of the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects aged 18 years or less who had non-clinically significant comparative genomic hybridization microarray results from January 2011 to December 2014. The primary end point was the yield of clinically significant next-generation sequencing results.
  
  
  
  Forty-nine subjects (21 male) with medication-refractory epilepsy and clinically in significant comparative genomic hybridization microarray results were identified. Next-generation sequencing abnormalities were seen in 28 subjects (57%): seven of these 28 subjects (25%) had clinically significant findings. Mutations were found in the SCN1A gene in three subjects, in the PCDH19 gene in two subjects, and in DLG3, MECP2, TSC2, and SLC9A6 genes in one subject each. Only the MECP2 mutation was found to be pathogenic in this last subject. The additional yield of next-generation sequencing with uninformative chromosomal microarray was 14%. Positive findings were primarily seen in those with Dravet syndrome, all with SCN1A mutations (42% of clinically significant results). Given the small sample size, a larger prospective study would help to determine the clinical yield of next-generation sequencing.
  
  
  
  Next-generation sequencing seizure panels could be a useful tool in the diagnosis of nonacquired pediatric medication-refractory epilepsy with uninformative comparative genomic hybridization microarray.
authors.affiliation: Northeast Regional Epilepsy Group, Hackensack, New Jersey. Electronic address: esegal@epilepsygroup.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Segal
authors.affiliation: Division of Genetics, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Helio
authors.initials: H
authors.lastname: Pedro
authors.affiliation: Division of Genetics, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Karen
authors.initials: K
authors.lastname: Valdez-Gonzalez
authors.affiliation: Division of Genetics, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Sarah
authors.initials: S
authors.lastname: Parisotto
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Felicia
authors.initials: F
authors.lastname: Gliksman
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Stephen
authors.initials: S
authors.lastname: Thompson
authors.affiliation: Northeast Regional Epilepsy Group, Hackensack, New Jersey.
authors.forename: Jomard
authors.initials: J
authors.lastname: Sabri
authors.affiliation: Northeast Regional Epilepsy Group, Hackensack, New Jersey.
authors.forename: Evan
authors.initials: E
authors.lastname: Fertig
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D000069279:Drug Resistant Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D046228:Microarray Analysis; D012189:Retrospective Studies
keywords: children; epilepsy; gene panel; next-generation sequencing