Rett syndrome (RS) is an X-linked dominant disorder that occurs almost entirely in females and has a prevalence of 1 in 9000 to 15,000. RS is caused by sequence variants in the methyl CpG binding protein 2 (MECP2) gene, which is located on the X chromosome. Typically, RS is observed as a progressive developmental disorder that appears in apparently normal girls at 6 to 18 months of age. After an initial period of slowing of normal development, developmental stagnation with decelerating head growth is often seen, usually followed by loss of acquired skills, including speech, motor skills, purposeful hand use, and social interaction. A set of clinical diagnostic criteria for classic and variant RS have been developed. The clinical symptoms of RS are highly variable, 1 of the causes of which being the pattern of X-chromosome inactivation (XCI). Initially, RS was thought to occur only in females; however, occasional cases of males with RS have been described. In addition to causing RS, sequence variants in the MECP2 gene have been associated with a variety
of other developmental disorders in both males and females. Sequence variants in the MECP2 gene generally cause a loss of function of the MECP2 protein; however, duplication of the MECP2 gene in males causes a form of X-linked intellectual disability. No treatment exists for RS or other disorders caused by MECP2 sequence variants, and management of emergent symptoms is the mainstay of therapy.