MECP2-related disorders in females include classic Rett syndrome and atypical Rett syndrome. These are both progressive neurodevelopmental disorders primarily affecting females, although some cases affecting males have been reported. Typically affected individuals have normal development up to the first 6 to 18 months of life, followed by developmental plateau, then rapid regression and loss of motor and language skills. Other associated features include acquired microcephaly, autistic-like features, stereotypic hand movements, autistic-like features, bruxism, gait apraxia, seizures. Atypical Rett syndrome may have either milder or more severe features compared to typical Rett syndrome.

Mutations in the MECP2 gene have been found to cause both Rett syndrome and atypical Rett syndrome. Males with mutations in this gene may have more severe features such as severe neonatal encephalopathy to a wide variety of neuropsychiatric features, cognitive impairment, spasticity and global developmental delay.