Abstract Details

Title Assessing the Clinical and Treatment Landscape of Genetic Epilepsies Through 3,760 Individuals

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S24 - Epilepsy Clinical Syndromes and Management (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background

Epilepsies with a presumed genetic basis account for up to two thirds of all epilepsies. A genetic diagnosis can inform personalized treatment strategies, however real-world practice is variable and the degree to which identification of an etiology translates into evidence-based treatment changes remains relatively uncharacterized.

Objective To delineate disease trajectories and longitudinal treatment landscapes in genetic epilepsies through Real-World Data captured from routine clinical care.

Design/Methods We retrospectively assessed the clinical data of individuals with epilepsy and neurodevelopmental disorders seen at a large pediatric healthcare network across 3 years. The impact of a genetic diagnosis on subsequent clinical management was reviewed, including referrals to specialty care and epilepsy surgical evaluations and modifications to treatment strategies. Seizure outcomes across epilepsy syndromes and distinct genetic etiologies were assessed using a Common Data Element-based framework.

Results We included 3,760 individuals with epilepsy and neurodevelopmental disorders and analyzed clinical data across 6,818 patient encounters. The median age of study inclusion was 6.4 years, with a median age of diagnosis of 3.1 years. 1,140/3,705 (30.8%) had a genetic diagnosis, representing 370 unique genetic etiologies including recurrent chromosomal abnormalities. The most common genetic etiologies included STXBP1 (n=89), SCN1A (n=62), and SCN2A (n=44), while the most frequent diagnoses were SCN1A (n=18), KCNQ2 (n=17), and PRRT2 (n=12). Seizure frequencies were assessed for 2,311 individuals across 1,625 cumulative patient-years, and epilepsy trajectories were characterized with respect to distinct epilepsy syndromes and etiologies. Systematic evaluation of adjustments in clinical management after a genetic diagnosis demonstrated measurable effects, including changes in treatment practices.

Conclusions

Our study provides an unbiased view of the dynamic clinical and treatment landscape through a large-scale data approach. We demonstrate measurable effects in clinical care following a genetic diagnosis and establish a systematic framework for quantifying genetic evaluations and epilepsy outcomes for future precision medicine avenues.

Authors/Disclosures
Julie Xian PRESENTER	No disclosure on file
Michael Kaufman	No disclosure on file
Sarah Ruggiero	No disclosure on file
Mark Ramos (Children's Hospital of Philadelphia)	No disclosure on file
Alexander Gonzalez	No disclosure on file
Amanda Back (Children's Hospital of Phialdelphia)	No disclosure on file
Lea Bailey-Medley (Children's Hospital of Philadelphia)	No disclosure on file
Stacey Cohen	No disclosure on file
Vishnu A. Cuddapah, MD (Children's Hospital of Philadelphia)	The institution of Dr. Cuddapah has received research support from NIH. The institution of Dr. Cuddapah has received research support from CURE Epilepsy.
Colin A. Ellis, MD (University of Pennsylvania)	Dr. Ellis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Epiminder.
Natalie Ginn (Children's Hospital of Philadelphia)	No disclosure on file
Naomi Lewin, MD (Children's Hospital of Philadelphia)	Dr. Lewin has nothing to disclose.
Laina Lusk	No disclosure on file
Eric D. Marsh, MD, PhD (Children's Hospital of Philadlephia)	Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmacuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from NIH. The institution of Dr. Marsh has received research support from Rett Syndrome Research Trust. The institution of Dr. Marsh has received research support from International Rett Syndrome Foundation. The institution of Dr. Marsh has received research support from Eagles Autism Challenge. The institution of Dr. Marsh has received research support from LouLou Foundation. The institution of Dr. Marsh has received research support from International CDKL5 Resarch Foundation. The institution of Dr. Marsh has received research support from Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from Marinus. The institution of Dr. Marsh has received research support from Stoke Therapeutics. The institution of Dr. Marsh has received research support from Takeda Pharmaceuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Grant Review with NIH. Dr. Marsh has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Witness with Department of Human Services. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Medscape.
Shavonne Massey, MD (Children'S Hospital of Philadelphia)	Dr. Massey has a non-compensated relationship as a consultant with Sun Pharmaceutical Ltd that is relevant to AAN interests or activities.
Xilma R. Ortiz-Gonzalez, MD, PhD (CHOP Neurology)	The institution of Dr. Ortiz-Gonzalez has received research support from Robert Wood Johnson Foundation . The institution of Dr. Ortiz-Gonzalez has received research support from NINDS.
Pamela Pojomovsky McDonnell, MD (The Children'S Hospital of Philadelphia)	Dr. Pojomovsky McDonnell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Connected Research. Dr. Pojomovsky McDonnell has received research support from AAN.
Katie Rose Sullivan (Children's Hospital of Philadelphia)	No disclosure on file
Katherine Taub	No disclosure on file
Sarah F. Tefft (Children'S Hospital of Philadelphia)	Ms. Tefft has nothing to disclose.
Katherine Helbig	No disclosure on file
Ethan M. Goldberg, MD, PhD (The Children's Hospital of Philadelphia)	Dr. Goldberg has nothing to disclose.
Ingo Helbig	No disclosure on file
Mark P. Fitzgerald, MD, PhD (Children's Hospital of Philadelphia)	Dr. Fitzgerald has nothing to disclose.