Abstracts

Rationale: Targeted treatment in developmental and epileptic encephalopathies is an ongoing goal in precision medicine trials. While objective outcome measures in such trials including seizure frequency are easily quantifiable, assessing subjective measures such as Quality of Life and disease severity is complex. In our study, we aimed to summarize Quality of Life and its determinants in individuals with developmental and epileptic encephalopathies through a dedicated questionnaire.

Methods: An online questionnaire was developed based on validated measures and frameworks used in related neurodevelopmental disorders including QI-Disability (Downs et al 2019) and Severity Assessment in CDKL5 Deficiency Disorder (Demarest et al 2019). The questionnaire was administered through a secure online platform (REDCap) to caregivers of individuals with developmental and epileptic encephalopathies identified through participating patient advocacy organizations between September 21, 2020 and December 17, 2020. The questionnaire included 89 items addressing demographic information, genetic diagnosis, and clinical features including seizure and non-seizure features of disease. Quality of Life items were used to generate a composite score.

Results: We received 176 questionnaire responses. The most common genetic diagnoses reported were SCN2A (n=42), SLC6A1 (n=28), SCN1A (n=22), and KCNQ2 (n=21). Composite Quality of Life scores showed a wide range centered around a mean score of 58.86 of 100 (IQR 48.61-69.36), corresponding to a mean of 9 reported symptoms (IQR 7-12). Quality of Life scores were not associated with seizure frequency or longest period of recent seizure freedom, but they were strongly associated with the number of days minimally disrupted by seizures, medication side effects, genetic diagnosis, and community type (rural, suburban, and urban living environments). The mean Quality of Life score for our population of individuals with developmental and epileptic encephalopathies was significantly lower than for individuals with other neurodevelopmental disorders including Rett syndrome, cerebral palsy, autism spectrum disorder, and Down syndrome.

Conclusions: Quality of Life in individuals with developmental and epileptic encephalopathies can be assessed through a standardized instrument combining established measures and disease-specific items. Quality of Life in this population is not related to objective seizure frequency, but rather the number of days minimally disrupted by seizures. Our data suggests that Quality of Life only partially overlaps with objective measurements of disease severity and may represent an independent outcome measure in future precision medicine trials.

Funding: Please list any funding that was received in support of this abstract.: Full funding for this project was received for the purpose of survey incentives from the National Society of Genetic Counselors, Neurogenetics Special Interest group.