Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

Abstract

ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.ObjectiveTo evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.ExposuresGenetic test results.Main Outcomes and MeasuresClinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms.ResultsAmong 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%).Conclusions and RelevanceResults of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Early genetic testing in pediatric epilepsy: Diagnostic and cost implications

“…A recent study found that genetic diagnoses in patients with epilepsy was associated with changes in clinical management in 49.8% of individuals and usually (81.7% of the time) within 3 months of receiving the result. 2 Thus early MEP testing may have implications for prompt changes to clinical care, including implementation of targeted treatment strategies. 3 Non-diagnostic metabolic testing and invasive procedures occurred more frequently in those individuals who underwent late compared with early genetic testing after clinical epilepsy diagnosis.…”

Utility of Exome Sequencing for Diagnosis in Unexplained Pediatric-Onset Epilepsy

“…We were also limited in our interpretation by lack of parental data for some patients, but we chose to include all individuals regardless of parental availability. Furthermore, as with a recent study reporting clinical utility of epilepsy panels, our EMR-based assessment could not accurately determine impact on hospitalization rates, morbidity or mortality, clinical trials eligibility, and avoidance of testing procedures (such as lumbar puncture, magnetic resonance imaging, or electroencephalography).…”

Familial Epilepsy Associated with Concurrent CHRNB2 Mutation and RBFOX1 Exon Deletion

“…Genetic ndings will provide valuable insight into the natural history of epilepsy heterogeneity. Most recently, the awareness of the impact of genetic background on developing drug-resistant epilepsy has gradually increased, and new genetic techniques are proving very useful in clinical practice and may help clinicians to explain the clinical presentation of drug-resistant epilepsy [13]. In addition, this will likely help us understand the impact of personalized and precise pharmacological treatment on epilepsy [14].…”