title: Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study.
abstract: BACKGROUND
  The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined.
  
  
  OBJECTIVE
  To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center.
  
  
  METHODS
  We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES).
  
  
  RESULTS
  We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29).
  
  
  CONCLUSIONS
  We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing.
authors.affiliation: Duke University Medical Center, Department of Pediatrics, Division of Pediatric Neurology, USA.
authors.forename: Margie A
authors.initials: MA
authors.lastname: Ream
authors.affiliation: Duke University Medical Center, Department of Pediatrics, Division of Pediatric Neurology, USA. Electronic address: mohamad.mikati@duke.edu.
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Mikati
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D010372:Pediatrics; D010641:Phenotype; D010865:Pilot Projects; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants
keywords: Drug-resistant epilepsy; Epileptic encephalopathy; Exome sequencing; Genetic testing; Pediatric epilepsy