Disease Impact and Burden in Patients with SCN2A-Related Developmental and Epileptic Encephalopathy (P11-9.012)

Abstract

<h3>Objective:</h3> Explore the burden of <i>SCN2A</i>-DEE on patients and caregivers using clinical data generated via a novel, patient-consented, real-world data platform. <h3>Background:</h3> <i>SCN2A</i>-related DEE comprises a subset of rare neurodevelopmental genetic disorders characterized by significant heterogeneity and limited understanding of disease burden and progression. <h3>Design/Methods:</h3> Real-world clinical data were extracted from patients with an <i>SCN2A</i> variant using Invitae’s Ciitizen platform, which employs a proprietary approach combining machine learning and expert human review to streamline generation of research-grade data from unstructured health records spanning ~10 years. Extracted data (seizure history, medications, comorbidities, developmental milestones) were classified by phenotype based on age at seizure onset, type of seizure at initial presentation, variant type and functional characterization using dynamic action potential clamp analysis. <h3>Results:</h3> 45 patients (92%) had data available for analyses. Four phenotypes were identified across three groups: early onset (EO, 33.5%), late onset (LO, 42%), and autism without epilepsy (AO, 24.5%). The LO group contained two distinct phenotypes based on age and type of seizure at onset: the first, characterized by initial seizure presentation with infantile spasms (LOIS, 20%); the second characterized by seizures other than infantile spasms and presenting later in life (LO, 22%). Mean patient age across cohorts was 8 years (0.8–23.3), with similar percentages of males and females. Mean age at seizure onset was 5.1 days (1–44) in the EO group. 53% of patients with seizures experienced status epilepticus at least once. Mean number of medications prescribed over a patient’s lifetime was 18.1 (0–58). Patients had multiple comorbidities, with global developmental delay the most common (97%), and hypotonia, GERD, autism, and sleep disorders reported in &gt;50%. All patients did not meet at least one critical developmental milestone. <h3>Conclusions:</h3> Using a novel real-world data platform and functional variant characterization, we provide unprecedented insight into clinical phenotypes, disease burden and treatment patterns in <i>SCN2A</i>-DEE. <b>Disclosure:</b> Kelley Dalby has received personal compensation for serving as an employee of Praxis Precision Medicines. Kelley Dalby has stock in Praxis Precision Medicines. Kelley Dalby has stock in RogCon. Mr. Snyder has received personal compensation for serving as an employee of Praxis Precision Medicines. Mr. Snyder has received stock or an ownership interest from Praxis Precision Medicines. Dr. G Matthews has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Dr. G Matthews has stock in Praxis Precision Medicines. Ms. Brimble has received personal compensation for serving as an employee of Invitae. Ms. Brimble has stock in Invitae. Ms. Brimble has stock in Ciitizen. Mr. Beek has received personal compensation for serving as an employee of invitae. Mr. Beek has stock in invitae. Ms. Berk has received personal compensation for serving as an employee of Invitae. Ms. Berk has stock in Invitae. Dr. Oldham has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has stock in Praxis Precision Medicines. Steven Petrou has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Steven Petrou has stock in Praxis Precision Medicines. The institution of Steven Petrou has received research support from Praxis Precision Medicines. The institution of Steven Petrou has received research support from Medical Research Future Fund. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care.