Neurodevelopmental Disorders Caused by Genetic Defects in Structure of Glutamatergic Receptors

Abstract

Background: the role of glutamate receptor dysfunction in mental disorders, neurological, autoimmune, and oncological pathology has been intensively investigated in the past decade. The development of drugs that target glutamatergic receptors has also been a focus of research.The aim was to describe modern concepts of neurodevelopmental disorders (according to the International Classification of Diseases 11th revision, L1-6A0) that are associated with genetically induced alterations of the structure of glutamatergic receptors.Material and method: a search for descriptions of cases with impaired neuropsychiatric development associated with genetic defects of ionotropic and metabotropic glutamate receptor subunits was performed in the MEDLINE/Gene database, MEDLINE/PubMed scientific library, Online Mendelian Inheritance in Man (OMIM), UniProt, ClinGen and eLibrary. Genetically induced structural abnormalities of most known ionotropic (GluA, GluN, GluK, GluD) and a number of metabotropic glutamate receptors (mGluR1, 5, 7) are associated with severe variants of neuropsychiatric disorders that manifest in infancy and early childhood.Conclusion: the considerable variation in the clinical presentation of these cases demands a transnosological approach to diagnosis and management of patients, under cooperation of specialists in pediatrics, child psychiatry, neurology, genetics, and medical and social rehabilitation.