Improving Diagnosis of Early-life Epilepsy
Over the last decade, genetic testing has become more common as part of the evaluation for pediatric epilepsy. Often, we turn to genetic testing in hopes of better understanding the cause of epilepsies, which have defied diagnosis after a thorough exam, EEG, imaging and laboratory tests. Understanding the genetic basis can impact treatment.
As increasing genetic etiologies have been identified, particular targeted treatments may improve outcomes. For example, the ketogenic diet may prove more efficacious for GLUT1 deficiency, whereas antiepileptic drugs with sodium channel mechanisms of action, may worsen the epilepsy in patients with SCN1A mutations. In addition, discovering a genetic etiology can help inform parents with regards to recurrence risk in future children. It also informs physicians of potential comorbid conditions, which might arise over the course of the disorder. While the literature in pediatric epilepsy has exploded with advancements in genetic testing, as well as identifying new genetic markers, the indications for when this testing is most valuable are lacking.
The Jane and John Justin Neurosciences Center at Cook Children's has been a member of the Pediatric Epilepsy Research Consortium (PERC), a national research network of more than 40 pediatric epilepsy centers, since January 2013. As part of this consortium, Cynthia Keator, M.D., has served as the principal investigator of several studies evaluating the etiologies, diagnosis and treatment of early-life epilepsy and has recently published two papers detailing the role and yield of genetic testing in these patients. In their most recent publications, the group demonstrated that genetic testing was commonly obtained in children with early-life epilepsies when an etiology was not evident after history, exam and brain imaging (MRI).(1) When genetic testing was obtained (typically in the form of chromosomal microarray or multiple gene panels), a diagnosis was found in 40% of the patients, which was similar to the number that had etiology identified with imaging (38%) and better than those diagnosed by other metabolic lab testing (4%).(1) In addition, among 180 patients that had no etiology identified by imaging and metabolic testing, 26% had a pathogenic genetic etiology identified. A previous study by the same group demonstrated that when genetic testing was employed in evaluation of infantile spasms it was also more useful than metabolic lab work. (2)
Genetic testing will become a common component of evaluating epilepsy and Cook Children's Neurosciences remains committed to defining the populations that will benefit most from this diagnostic approach. When there is an unknown etiology in early-life epilepsies, an early diagnosis with genetic testing may guide better treatment, potentially improve outcomes and decrease costs by eliminating the need for unnecessary testing such as repeated MRIs, EEG and lab work.
(1) Berg AT, Coryell J, Saneto RP, Grinspan ZM, Alexander JJ, Kekis M, Sullivan JE, Wirrell EC, Shellhaas RA, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Dobyns WB, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Koh S. Early-Life Epilepsies and the Emerging Role of Genetic Testing. JAMA Pediatr. 2017 Sep 1;171(9):863-871.
(2) Wirrell E, Shellhass R, Joshi C, Keator C, Kumar S, Mitchell W, and the Pediatric Epilepsy Research Consortium. How Should Children with West Syndrome be Efficiently and Accurately Investigated? Results from the National Infantile Spasms Consortium. Epilepsia, 56(4):617-625,2015.