Rett Syndrome: A Prototypical Neurodevelopmental Disorder

Abstract

Rett syndrome, one of the leading causes of mental retardation and developmental regression in girls, is the first pervasive developmental disorder with a known genetic cause. The majority of cases of sporadic Rett syndrome are caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 binds methylated DNA and likely regulates gene expression and chromatin structure. Genotype/phenotype analysis revealed that the phenotypic spectrum of MECP2 mutations in humans is broader than initially suspected: Mutations have been discovered in Rett syndrome variants, mentally retarded males, and autistic children. A variety of in vivo and in vitro models has been developed that allow analysis of MeCP2 function and pathogenic studies of Rett syndrome. Because the neuropathology of Rett syndrome shares certain features with other neurodevelopmental disorders, a common pathogenic process may underlie these disorders. Thus, Rett syndrome is a prototype for the genetic, molecular, and neurobiological analysis of neurodevelopmental disorders.