Genetic Etiology of Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) are a set of complex and heterogeneous psychiatric conditions that involve abnormalities in the development of the brain and central nervous system that begin early in life. These disorders are generally categorized as intellectual disorder, attention-deficit/hyperactivity disorder, specific learning disorder, and autism spectrum disorder. As neurodevelopment is a long-lasting intrauterine pathway that is affected by both genetic and epigenetic determinants, a wide range of genetic factors, ranging from mutations to chromosomal abnormalities and copy number variations, are responsible for the etiology of a significant percentage of NDDs. In recent years, considerable progress has been made in identifying the specific biological pathways underlying these disorders’ molecular mechanisms, and a large number of genes have been identified that play a role in causing these disorders. However, the pathogenesis of NDDs is still far from being fully understood. Although the results of studies investigating the genes responsible for NDDs vary widely due to the heterogeneity of NDDs, there are some consistent findings regarding genetic factors in the etiology of NDDs, both for common and distinct NDD types. Numerous genetic databases including SPARK, SFARI Gene, SysID, DBD, and DDG2P have provided important data to group genes into categories that are clinically useful. These studies have led to a better understanding of the relationship between mutations, clinical profiles, and mechanisms for a number of genes that are frequently mutated in NDD patients, such as FMR1, PTEN, SHANK3, and MECP2. In addition, variants causing NDD have been found in the ADNP, ARID1B, ANKRD11, CHD2, CHD8, CTNNB1, DYRK1A, SCN2A, DDX3X, and SYNGAP1 genes. As there is no specific treatment for NDDs, understanding the genetic mechanisms of NDDs is crucial for potential future therapeutic research.