Rett Syndrome: From MECP2 Dysfunction to Emerging Therapeutic Strategies
Abstract:
Rett syndrome is an uncommon and serious neurodevelopmental disorder, mainly seen in girls, and most often results from mutations in the MECP2 gene found on the X chromosome. After an initial period of normal develop ment, affected children undergo progressive neurological regression characterized by loss of acquired motor and language skills, stereotyped hand movements, respiratory abnormalities, epilepsy, and severe intellectual disability. The disorder reflects profound alterations in neuronal maturation, synaptic function, and neurotransmitter regula tion, highlighting the essential role of MECP2 as a global regulator of gene expression in the central nervous system. This review outlines the clinical features, genetic basis, and pathophysiological mechanisms of Rett syndrome, with particular emphasis on MECP2-related disorders and Rett-like syndromes. This article explores current diagnostic methods, treatments for symptoms, and new therapeutic options. These include drug therapies, gene therapy, reac tivation of the X chromosome, and targeting downstream factors like brain-derived neurotrophic factor (BDNF). Although no curative treatment is currently available, advances in molecular genetics and neuroscience offer prom ising perspectives for future disease-modifying therapies.
