Rett syndrome: clinical and molecular update

Purpose of review New information on the clinical and molecular aspects of Rett syndrome has emerged at an accelerated pace since the identification of mutations in methyl-CpG-binding protein 2 gene (MECP2) was first reported in 1999. Recent reports not only present new insights into the clinical and molecular understanding of this unique disorder but also have important implications for the neurobiology beyond Rett syndrome. Recent findings This review covers recent advances in Rett syndrome from clinical management issues to laboratory-based genetic discoveries. Summary Clinical management issues include electrocardiographic findings, scoliosis, osteopenia, and motor control. Interesting phenotype-genotype correlations have resulted from the recognition of large-scale deletions in MECP2 as a cause of Rett syndrome, and the more recent identification of an alternate splicing isoform of the gene product. These are beginning to provide a more coherent picture of the spectrum of disease caused by mutations in,MECP2. The neurobiologic role of the MECP2 gene in Rett syndrome and normal development has been greatly elucidated with the development of animal models of Rett syndrome and the study of MECP2 in humans and rodents.