Abstracts

Rationale: Genetic testing is being utilized more widely in pediatric epilepsy cases to achieve an accurate diagnosis and inform medical management, when possible. However, there is great variability in the use of genetic testing for adult patients with epilepsy. We explored genetic testing patterns and diagnostic yield in adult epilepsy cases. Methods: All sequential cases submitted for epilepsy multi-gene panel testing (MGPT) between December 2015 and February 2017 were retrospectively identified. Available clinical data and genetic test results were reviewed for all cases 18 years of age or older at of the time of testing. Results: Fifty-eight cases were included in analysis. Six (10%) cases were reported to have adult-onset seizures (range 20 – 63 years), while the remainder had seizure onset in childhood. A history of refractory epilepsy was reported in half (50%) of cases. The most commonly reported seizure types were tonic (16/58), generalized tonic-clonic (15/58), and focal (12/58). Seven (12%) cases were reported to have a previously diagnosed epilepsy syndrome, including Lennox-Gastaut Syndrome (LGS), Generalized Epilepsy with Febrile Seizure plus (GEFS+), and Juvenile Myoclonic Epilepsy (JME). Developmental delay was reported in 19 (33%) cases and intellectual disability (ID) in 18 (31%). Other clinical findings included movement disorders (7/58) and psychiatric disorders (7/58). The majority (71%) of cases had previous electroclinical testing, including abnormal EEG (41%) and/or abnormal/inconclusive brain MRI (31%). Only six (10%) had previous epilepsy genetic testing.Five cases (9%) were found to have pathogenic or likely pathogenic alterations, one each in DEPDC5, PRRT2, SCN1A, SCN1B, and STX1B. Interestingly, an SCN1B alteration confirmed a previous GEFS+ diagnosis in one patient with febrile seizures (onset age 9 months) and strong maternal family history of febrile seizures. Also, an alteration in STX1B was detected in one patient with no previous epilepsy syndrome diagnosis, history of generalized tonic clonic and focal seizures (onset in infancy), and intellectual disability, as well as strong paternal family history of childhood seizures, consistent with a diagnosis of GEFS+ type 9. Additionally, a SCN1A alteration was detected in a patient with a personal history of intellectual disability and refractory unclassified seizures (onset at 22 years). Limited personal and family history was provided for the remaining two cases with detected alterations. Conclusions: MGPT can provide a useful tool during the diagnosis and management of adult patients with epilepsy. It can be particularly helpful in confirming previous epilepsy syndrome diagnoses and inheritance patterns, which may have important reproductive implications for patients. In addition, it can provide neurologists with valuable information regarding gene-targeted treatment options, predicted treatment response, and potential lifestyle changes to decrease seizure frequency and ensure quality of life. Funding: None