Disorders of Nervous System Development

Neurodevelopmental disorders are chronic disorders that affect the function of the central nervous system (CNS) and impair motor skills, cognition, communication and/or behavior. While these disorders frequently stem from mutations in genes that directly control CNS development, they can also be a consequence of environmental insults such as hypoxic/ischemic injury, trauma, exposure to toxins, infections and nutritional deficiencies, or be indirectly caused by mutations in metabolic genes (reviewed by Ismail and Shapiro 2019). Disorders of nervous system development have been traditionally classified based on phenotypic traits (clinical presentation). Molecular genetics studies have revealed, however, that indistinguishable clinical presentations may result from pathogenic variants in different genes whose protein products function in connected biological pathways. On the other hand, distinct clinical presentations may be caused by pathogenic mutations in a single gene that functions in multiple biological pathways. In the future, phenotype-based classification of neurodevelopmental disorders may be replaced by a more informative pathway-based nomenclature. Biological pathways frequently impaired in neurodevelopmental disorders are signal transduction pathways such as the mTOR pathway in tuberous sclerosis complex (TSC) and the RAS/RAF/MAPK pathway in RASopathies, neurotransmission pathways as in some autism spectrum disorders (ASD), and pathways that regulate gene expression as in Mendelian disorders of epigenetic machinery (MDEM).

Summary from Reactome (R-HSA-9697154), read 2026-09-23.