Abstract Details

Title Characteristics of a Nationwide Cohort of Patients with Developmental and Epileptic Encephalopathy Disease-causing Genotypes

Topic Child Neurology and Developmental Neurology

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 8-002

Objective To describe a nationwide cohort of patients with disease-causing genotypes in genes associated with developmental and epileptic encephalopathies (DEEs).

Background DEEs are conditions characterized by seizures and developmental delay. Increasingly, genotype drives diagnosis, treatment, and clinical trial options.

Design/Methods Retrospective chart review of patients with disease-causing genotypes in DEE-associated genes referred to a nationwide telehealth genetic counseling practice.

Results Between 2019 and 2025, 269 patients with disease-causing genotypes in 66 DEE genes were referred. Most patients were children (190/269, 70.6%) at the time of visit, and 54.6% (147/269) were female. The median age was 3 for children (IQR 1-7) and 38 for adults (IQR 27.5-39). Patients resided in 46 states, most frequently Texas (27/269, 10.0%), California (23/269, 8.6%), and Florida (19/269, 7.1%). Variants occurred most frequently in SCN1A (27/269, 10.0%), CACNA1A (16/269, 5.9%), and TSC2 (15/269, 5.6%). Among those with parental genetic testing, 61.5% (40/65) had a de novo variant. The inheritance pattern was autosomal dominant (226/269, 84.0%), X-linked (33/269, 12.3%), autosomal dominant/recessive (8/269, 3.0%), and autosomal recessive (2/269, 0.7%). Data on DEE features were extracted from clinic notes if available: 86.3% (169/196) had known or suspected seizures, 72.1% (127/176) had developmental delay, 62.8% (27/43) had intellectual disabilities, and 23% (20/85) had structural brain abnormalities. The age of first seizure was under 1 year for 55.6% of patients with seizures (65/117). Median time from first seizure to molecular diagnosis was 1 year (IQR 0-6).

Conclusions This nationwide cohort highlights the clinical and genetic heterogeneity of DEEs, underscoring the value of genotype-driven care and the broad geographic reach of telehealth genetics.

Authors/Disclosures
Sara Riordan, CGC PRESENTER	Ms. Riordan has received personal compensation for serving as an employee of Genome Medical. Ms. Riordan has or had stock in Genome Medical.
Nikol Nikolova	Ms. Nikolova has received research support from Jane Engelberg Memorial Fellowship.
Carly Fisher	Ms. Fisher has nothing to disclose.
Natalie Beck (Genome Medical)	Natalie Beck has nothing to disclose.
Colleen Caleshu, MS, CGC	Ms. Caleshu has received personal compensation for serving as an employee of Genome Medical. Ms. Caleshu has stock in Genome Medical.

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