Epigenetic processes in neurodevelopmental disorders

Epigenetic factors control the pattern of gene expression during brain development, introducing epigenetic modifications that can be maintained and transmitted from one cell generation to the next one or modified in response to external stimuli. Such modifications are fundamental for the correct timing and spatial regulation of the critical processes that follow one another during brain development. Proper DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs function are required for the formation of a functional cortex. Since epigenetic factors control the expression of multiple genes, their alteration usually has pleiotropic effects and impacts on multiple biologic processes. Alterations affecting epigenetic factors that are relevant for brain development translate into defects in key processes, including neuronal stem cell proliferation, differentiation and maturation, neuron migration, and synapse formation/function. The dysregulation of all these processes leads to neurodevelopmental disorders with different etiology, age onset, and severity of the clinical manifestations. Despite the heterogeneity of these disorders, neurodevelopmental disorders of different origin can feature overlapping phenotypes and common symptoms, depending on the neurodevelopmental mechanisms that are impacted by the specific altered epigenetic factor.