2025 American Academy of Neurology Abstract Website

Objective:

To characterize the spectrum of clinical needs with respect to neurological, developmental, neuropsychiatric, and systemic comorbidities in genetically confirmed developmental and epileptic encephalopathies (DEEs).

Background:

Genetic developmental and epileptic encephalopathies (DEEs) represent a class of severe neurological disorders characterized by early-onset seizures and neurodevelopmental abnormalities in the setting of monogenetic etiology. While seizures are the predominant clinical feature in these disorders, understanding the underlying burden of clinical care is important for providing optimal clinical care.

Design/Methods:

A retrospective chart review was conducted on patients with genetically confirmed DEE over a period of 5 years (2019-2024). Clinical information relating to phenotypes and specialist clinical care utilization was reviewed.

Results:

Fifty-eight patients with pathogenic/likely pathogenic variants linked to genetic DEEs were included. Monogenic diagnoses included SCN1A (10), PRRT2 (9), KCNQ2 (9), CACNA1A (5), and 18 other genes with 1–3 patients each. The mean age of cohort was 6.8 +/- 6.5 years. SCN1A (10), KCNT1 (1), ARX (1), CACNA1A (5), GABRA1 (2)- related DEEs were associated with the highest seizure burden, medication-resistant seizures and frequent hospitalizations. Patients with PRRT2 (56%, 5 of 9) and KCNQ2 (44%, 4 of 9) had prominent gastrointestinal comorbidities (constipation). SLC6A1 (1), GABRB3 (1), and CHD2 (1) were associated with predominance of neurodevelopmental delays and neuropsychiatric disorders (Autism, ADHD, aggression). All 58 patients (100%) needed epilepsy care, 38 (66%) received neurodevelopmental therapies and 28 (48%) required neuropsychiatric care. Nineteen (33%) required sub-specialist care with gastroenterology, 17 (29%) with sleep medicine, 15 (26%) with pulmonology, 11 (19%) with ophthalmology, 6 (10%) with cardiology, and 6 (10%) with urology.

Conclusions:

The heterogeneity in seizures, neurodevelopmental, neuropsychiatric and systemic abnormalities in patients genetic DEEs underscores the need for individualized clinical approaches. Our results advocate for tailored clinical care coordination strategies for specific genetic DEEs with emphasis on neuropsychiatric and systemic comorbidities in addition to epilepsy.