Abstracts

Rationale: Genetic epilepsy syndromes are characterized by early seizure onset and poor response to intervention. Given their relative rarity, management guidelines are limited or non-existent. In this work, we leverage a novel real world data platform to describe the epilepsy phenotype and treatment patterns in a large cohort of individuals with SYNGAP1-related disorder.

Methods: Ciitizen is a patient-facing platform that collects designated record sets by leveraging the HIPAA right of access. Record completion was verified through evaluation of document class and encounter year. Ciitizen’s data model supports systematic capture of relevant clinical phenotypes and interventions. Extracted data were harmonized by use of standard terminologies. Cohort features were analyzed using descriptive statistics.

Results: Data were extracted from the medical records of 80 individuals with a likely pathogenic or pathogenic variant in SYNGAP1. The average age of participants was 9.7 ± 8.6 years (range 2-65) with a near equal distribution of males (52.5%) and females (47.5%). Most individuals had truncating variants (n=63, 78.8%). An average of 249.4 ± 278.3 documents were reviewed per participant, representing 8.1 ± 4.9 years of data.

Epilepsy was diagnosed in 71 (88.8%) participants with an average age of onset of 43.8 months (range 0-211). Of those with epilepsy, 16 (22.5%) were classified as having an epileptic encephalopathy, with Lennox-Gastaut syndrome most common (n=12). The most frequently described seizure types were generalized, including: absence (n=36, 56.3%), atonic (n=36, 56.3%), and atypical absence (n=18, 28.1%) seizures. In support, those with documentation of at least one electroencephalogram (n=76, 95%) had primarily generalized epileptiform activity (n=62, 81.6%) in addition to background abnormalities (n=49, 61.3%). There were 31 unique antiepileptic drugs (AEDs) documented for this cohort, averaging 5.1 ± 3.0 AEDs per individual with epilepsy (range 1-16). The most common AEDs were: levetiracetam (n=41, 57.8%), clobazam (n=39, 54.9%), lamotrigine (n=39, 54.9%), and valproate (n=36, 50.7%). The average number of concurrent unique AEDs peaked at 4 years of age (1.69 ± 1.71). A therapeutic diet was used in 13 (18.3%), with the ketogenic diet most common. Surgical interventions for epilepsy management included vagus nerve stimulation (n=7, 9.9%) and corpus callosotomy (n=3, 4.2%).

Developmental and behavioral phenotypes reported in this cohort include: global developmental delay (n=75, 93.8%), intellectual disability (n=44, 55%), and autism spectrum disorder (n=53, 66.3%). Behavioral challenges were described in 64 (80%), including aggressive and self-injurious behaviors. Many individuals were described as having sleep difficulties (n=50, 62.5%), with 45 (56.3%) having tried a medication for sleep.

Conclusions: To our knowledge, this work represents the largest cohort of SYNGAP1-related disorder described to date, demonstrating the unique potential of real world evidence to expand understanding of rare epilepsy syndromes.

Funding: Please list any funding that was received in support of this abstract.: SynGAP Research Fund Ciitizen.