Abstracts

Rationale: Variants in the KCNQ2 gene underlie a spectrum of rare neonatal-onset epilepsies with varying severity, from self-limited forms to a more severe developmental and epileptic encephalopathy (KCNQ2-DEE). Due to its rarity, management recommendations for KCNQ2-DEE are based upon case series with often limited longitudinal data. The objective of this study was to evaluate real world data from a cohort of patients with KCNQ2-DEE, obtained via a novel data platform that aggregates patient medical records creating a complete picture of disease management.

Methods: Invitae’s Ciitizen platform is a patient/caregiver-consented platform that collects medical records by leveraging the HIPAA right of access. The data platform supports systematic capture of patient phenotypes, medical encounters and therapeutic interventions. The data from patients who have completed data capture before October 2022 will be included in the analysis. Data were extracted from the medical records of 7 patients captured to date with a molecular diagnosis and clinical presentation consistent with KCNQ2-DEE. Data completeness and recency were verified through a minimum of 3 rounds of human review based on encounter type and date; incomplete record sets were excluded from the dataset. Extracted data were harmonized by use of standard terminologies and validated through standardized review. Cohort features were analyzed using descriptive statistics.

Results: The average age of patients at the time of data delivery was 6.6 years (range, 2.5-16.3 years). In all patients, seizure-onset was within the first 15 days of life (range, 0-15 days), with focal seizures most frequently described at onset. All patients had multiple abnormal findings on EEG and video EEG at onset which will be described. 4 of 7 patients had a seizure documented within the past 6 months at the date of the last follow-up. There were 28 antiseizure medications (ASMs) documented for the 7 patients described so far, averaging 11 ASMs per patient (range, 3-21). Other phenotypes reported in the cohort include global developmental delay in all patients, motor function delay in 86% (6/7), GI-related issues in all patients, including 71% (5/7) with feeding difficulties or feeding tube dependency.

Conclusions: This novel platform has identified an emerging cohort of patients with KCNQ2-DEE and demonstrates the value of standardized medical record collection in genetically-defined cohorts. The evaluation of the unbiased, real-world data collected via this platform will provide unique insights into the patient journey, expand our understanding of rare epilepsy syndromes including KCNQ2-DEE, and better inform treatment strategies and prognosis. Interrogation of complete medical records for patients with rare genetic epilepsies can provide a more complete picture of the management strategy, common pitfalls and clinical challenges experienced by this patient population. 

Funding: Xenon Pharmaceuticals Inc.