Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing

This study evaluates the clinical utility of Long-read Whole Genome Sequencing (lrWGS) as a secondary diagnostic tool for Developmental and Epileptic Encephalopathies (DEEs). While current standard-of-care "short-read" sequencing (srWGS) is effective at identifying small genetic mutations, it often fails to detect complex structural changes, leaving over 50% of patients without a diagnosis. Technically, lrWGS overcomes these limitations by analyzing DNA fragments that are thousands of bases long. This allows researchers to map "dark regions" of the genome and identify Structural Variants (SVs), such as large insertions, deletions, or repeat expansions, which are often the hidden causes of severe epilepsy. By identifying these elusive genetic drivers, the study aims to move beyond a simple diagnosis toward precision medicine. A clear molecular result can directly influence clinical decisions, such as selecting targeted medications, avoiding contraindicated drugs, or determining eligibility for emerging gene therapies. Additionally, the project assesses the feasibility of integrating this technology into routine clinical practice by evaluating bioinformatic complexity and diagnostic turnaround times.