Novel Variants in PLPBP, SCN1A, and SLC6A1: Genetics, Bioinformatics, and clinical Elucidation of Three Distinct Cases of Developmental and Epileptic Encephalopathy.

Developmental and epileptic encephalopathies (DEEs) are severe early-onset disorders featuring refractory seizures, abnormal EEGs, and developmental delays. Clinically and etiologically heterogeneous, they include subtypes such as Dravet syndrome and EIMFS. An increasing number are recognized as etiology-specific, with distinct genetic causes corresponding to characteristic phenotypes, highlighting the need for thorough diagnostic evaluation. This study utilized a multidisciplinary diagnostic approach to investigate DEE. In this descriptive case series, the reported novel variants include a PLPBP duplication (c.596dup), an SCN1A insertion (c.3879dup), and an SLC6A1 in-frame deletion (c.943_945del). Bioinformatics and segregation analysis supported their pathogenicity, with each variant linked to a distinct clinical phenotype. The reported novel variants broaden the phenotypic and genotypic spectrum of these disorders and inform clinical management and genetic counseling.