SCN2A – a neurodevelopmental disorder digitized through 10,860 phenotypic annotations

HPO. SCN2A-related disorders represent one of the most common causes of neurodevelopmental disorders and developmental and epileptic encephalopathies (DEE). However, while a genetic diagnosis is easily made through high-throughput genetic testing, SCN2A-related disorders have such a broad phenotypic range that understanding the full scale of the clinical features has been traditionally difficult. In our recent study, we used a harmonized framework for phenotypes based on the Human Phenotype Ontology (HPO) to systematically curate phenotypic annotations in all individuals reported in the literature and followed at our center, a total of 413 unrelated individuals. Mapping phenotypic data onto 10,860 terms with 562 unique concepts and applying some of the computational tools we have developed over the last three years, we were able to delineate the phenotypic range in unprecedented detail. SCN2A is now the first DEE with all available data systematically curated and harmonized in a computable format, allowing for entirely novel insights. Continue reading