Title : Defining the genetic landscape of developmental and epileptic encephalopathy in Egyptian children using whole exome sequencing
Abstract:
Background: Developmental and epileptic encephalopathy (DEE) comprises a clinically and genetically heterogeneous group of severe childhood neurological disorders characterized by early-onset, often drug-resistant epilepsy accompanied by developmental delay or regression. In addition to seizures, affected children frequently experience intellectual disability, autism spectrum disorder, behavioural disturbances, sleep disorders, and other neurological comorbidities that substantially impair quality of life and impose a considerable burden on families and healthcare systems. Recent advances in next-generation sequencing have transformed the understanding of DEE, with more than 900 genes implicated in disease pathogenesis. Identifying the underlying molecular diagnosis has become increasingly important, not only for confirming the clinical diagnosis but also for informing prognosis, guiding precision therapies, and improving genetic counselling. However, the genetic spectrum of DEE remains poorly characterized in Egyptian and North African populations.
Objectives: This study aims to define the genetic landscape of developmental and epileptic encephalopathy in Egyptian children using Whole Exome Sequencing (WES). Secondary objectives include establishing genotype–phenotype correlations, identifying clinically actionable genetic variants, and evaluating the potential impact of molecular diagnosis on patient management, family counselling, recurrence-risk assessment, and prenatal diagnosis.
Methods: Twenty Egyptian children with clinically confirmed DEE will be recruited. Diagnosis will be supported by detailed clinical evaluation, electroencephalography, brain magnetic resonance imaging, and evidence of progressive neurodevelopmental regression. Genomic DNA extracted from peripheral blood samples will undergo Whole Exome Sequencing. Identified variants will be interpreted according to established pathogenicity criteria and analysed for their involvement in neuronal excitability, ion channel function, synaptic transmission, intracellular signalling, metabolic pathways, and epigenetic regulation. Molecular findings will be correlated with the clinical
phenotype to improve understanding of disease mechanisms and their clinical implications.
Expected Results: Whole Exome Sequencing is anticipated to identify pathogenic or likely pathogenic variants in a substantial proportion of patients, thereby improving molecular diagnostic yield within this cohort. The study is expected to expand current knowledge of the genetic architecture of DEE in Egyptian children, identify variants with potential therapeutic relevance, strengthen genotype–phenotype correlations, and facilitate implementation of precision medicine approaches. The findings are also expected to enhance genetic counselling, family planning, and
prenatal diagnostic services.
Conclusions: This study will provide one of the first comprehensive genomic characterizations of developmental and epileptic encephalopathy in Egyptian children. By integrating detailed clinical phenotyping with Whole Exome Sequencing, it aims to establish a foundation for precision neurology and genomic medicine in Egypt while contributing valuable data to the global understanding of DEE.
