Neurological diseases, including intellectual disability (ID), can be caused by disturbances in epigenetic regulation of specific genes that encode proteins necessary for appropriate central nervous system functioning. The “epigenetically caused” diseases can be due to the imprinting defects formed during germinal cells development or gained throughout life as a somatic changes. They can also result from abnormal functioning of transcriptional machinery caused by mutations in genes coding for specific proteins. Two most classical examples of disease caused by imprinting defect in germinal cells are Prader-Willi and Angelman syndromes, both characterized by ID and developmental delay. Both these diseases are caused by altered epigenetic regulation of genes localized on chromosome 15 (region q11–q13) that can be due to chromosome deletion or uniparental disomy. The other neurological disease that is related to abnormal epigenetic regulation is Fragile X syndrome characterized by ID and specific behavior. Almost all disease cases are due to the expansion of CGG repeat (>200) in the 5’UTR of FMR1 gene that leads to promoter methylation and lack of FMRP protein that is indispensable for neuron development and signaling. The example of neurological “epigenetic diseases” caused by altered transcriptional regulation is Rett syndrome caused by the mutation presence in MECP2 gene or its variant – Rett-like syndrome caused by the mutation in CDKL5 gene. Both these diseases are characterized by ID and childhood epilepsy. Herein, we present our experience from the research and diagnosis of above mentioned disorders in the context of neurological pathways altered by improper epigenetic regulation.
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