Abstracts

Rationale: Major advances in molecular genetics have resulted in the availability of a significant number of genetic testing modalities. The new technologies have contributed to the identification of a large number of epilepsy-related genes. However, the genetic diagnostic yield and clinical utility in “real life” clinical practice have been scarcely reported. The objective of this study is to determine the diagnostic yield and utility of genetic testing by Sanger sequencing or next-generation sequencing in a cohort of patients with Epileptic Encephalopathy (EE).Methods: We conducted a retrospective review of all patients with EE who were studied in our Genetic Epilepsies Unit from January 2008 until December 2014. The majority of patients had been previously studied in order to rule out a structural or metabolic etiology. Chromosomal rearrangements had also been excluded by karyotype or microarrays studies. Genetic testing included single gene sequencing, multigene panels, and/or whole exome sequencing (WES) depending on clinical judgment.Results: We included 118 patients. The syndromic diagnosis was West síndrome or non-lesional infantile spasms (27), Dravet or Dravet-like syndrome (12), Ohtahara syndrome o early myoclonic encephalopathy (10), unclassified EE (51), Lennox-Gastaut syndrome (6), Landau-Kleffner syndrome (4), EE with ESES (5), MAE (2) and malignant migrating partial seizures of infancy (1). Disease-causing mutations were found in 24 patients (20.3%): SCN1A (5 patients), KCNQ2 (4 patients), CDKL5 (3 patients), PCDH19 (3 patients), STXBP1 (2 patients), SLC2A1 (1 patient), KCNA2 (1 patient), GRIN1 (1 patient), ARX (1 patient), SYNGAP1 (1 patient), CNKSR2 (1 patient) and ALG13 (1 patient). Additionally a candidate gene was identified in a family with infantile spasms. The yield of each genetic test was: targeted single gene sequencing 10.9%, multigene panel 19.4% and WES 21%. Genetic diagnosis led to changes in therapy in two patients.Conclusions: In this study, the diagnostic yield using one or more available genetic test was 20% in patients with epileptic encephalopathy. A positive result is useful for genetic counseling, avoidance of unnecessary diagnostic procedures and in selected cases for choice of best treatment option.