Electroclinical phenotypes-genetic characterization of developmental and epileptic encephalopathies in a cohort study.

Objective

Developmental and epileptic encephalopathies (DEEs) are characterized by refractory seizures and frequently recurring epileptic activity with neurodevelopmental delay or regression that usually begin in early life. We aimed to define the relationship between electroclinical features and etiology, as well as the genotype-phenotype characterizations and prognosis with genetically determined DEEs.

Methods

We retrospectively evaluated patients with DEEs who were referred to the Division of Pediatric Neurology at our university hospital between 2017 and 2021 and followed for at least 24 months. Demographic characteristics, etiologies, genetic findings, and electroclinical phenotypes were analyzed in 136 children with DEEs.

Results

In our study, 50.7% of the patients were female. Age at presentation ranged from 1 to 126 months and the mean age at seizure onset was 9.4 months. Etiology was genetic in 41 patients (30.1%), structural in 32 patients (23.5%), and metabolic in 17 patients (12.5%). Among patients with a genetic etiology, 32 were genetically solved, including 28 with pathogenic or likely pathogenic single-gene variants and 4 with pathogenic copy number variants or chromosomal rearrangements. Eight additional patients had phenotype-concordant variants of uncertain significance, and one patient had a clinical-only genetic diagnosis. SCN1A was the most frequently affected gene. Electroclinical phenotypes in genetic DEEs were as follows: EIDEE in 11 patients, Dravet syndrome in 10, IESS in 6, EMAS in 2, LGS in 2, and unclassified in 10 patients.

Significance

We characterized DEEs with genetic etiology in our cohort and described their associated electroclinical phenotypes, including several novel variants in disease-associated genes. Understanding the diverse underlying etiologies of DEEs in children, along with their genotypic and phenotypic characteristics, is crucial for early diagnosis and treatment and the development of targeted management strategies.