Epigenetics in Psychiatry: Chapter 21 - Epigenetics in intellectual disability

Elsevier, Epigenetics in Psychiatry (Second Edition) 2021, Pages 489-517
Taryn Jakub, Katerine Quesnel, Crystal Keung, Nathalie G. Bérubé, Jamie M. Kramer

Intellectual disability (ID) is a neurodevelopmental disorder characterized by early onset limitations in intellectual functioning and adaptive behavior. Genetic and functional studies have revealed a role for epigenetics in the underlying pathology of ID. ID can result from aberrant epigenetic silencing of important neuronal genes or from mutations in core members of the epigenetic machinery. Aberrant epigenetic silencing occurs in the nucleotide repeat disorder, fragile X syndrome, and in the imprinting disorders Angelman syndrome and Prader–Willi syndrome. Mutations in epigenetic regulators are found in a diverse array of ID disorders, including Rett syndrome, ATR-X syndrome, Rubenstein–Taybi syndrome, and Kleefstra syndrome. There are over 70 ID genes encoding proteins that have a direct role in epigenetic regulation. These include genes encoding the molecular machinery that mediates DNA methylation, ATP-dependent chromatin remodeling, and posttranslational modification of histones. Here, we highlight research that has led to a greater understanding of how disruption of epigenetic regulation leads to cognitive deficits that are associated with ID.