Abstract

Rett Syndrome is a monogenic disorder linked to the X chromosome, of a progressive nature that affects neurodevelopment mainly in girls during the first stages of the life cycle. Its etiology is mainly due to loss-of-function single nucleotide change mutations of the MECP2 gene. This gene codes for the protein of the same name whose main function is to act as a global repressor of transcription through the recognition of methylated areas of CpG islands and the recruitment of corepressor factors that modulate gene expression by deacetylating histones. Among the main structural alterations associated with the syndrome are an atypical neuronal morphology with a size of the neuronal soma and a reduced number of dendritic spines, in addition to neurochemical alterations, especially in the GABAergic signal, leading to dysregulation between excitatory and inhibitory signals, causing epilepsy. A series of metabolic, oxidative, and inflammatory disorders have also been described. Until now, treatment has focused more on seeking symptomatic relief for the manifestations of the syndrome, but gene therapy has recently been developed with the aim of treating the pathology from its neurogenetic bases and thus avoiding altered development during childhood. © 2023 Authors. All rights reserved.