RETT SYNDROME: CURRENT STATUS AND NEW DIRECTIONS

Objective: To review the new information that has emerged on clinical and molecular aspects of Rett syndrome (RS) since mutations in methyl-CpG-binding protein 2 gene (MECP2) were first reported in 1999. Recent reports not only provide new insights into the clinical and molecular understanding of this unique disorder, but also have important implications for neurobiology beyond the boundaries of RS.

Results: This review will cover the rapidly expanding and wide range of recent advances in RS from clinical management issues to laboratory-based genetic discoveries. 1) a variety of clinical management strategies affecting females with RS have been addressed in the past year. These include electrocardiographic findings, scoliosis, osteopenia, and motor control; 2) the recognition of large scale deletions in MECP2 as a cause of RS and the more recent identification of an alternate splicing pattern resulting in an isoform of MeCP2 have led to interesting phenotype-genotype correlations. These are beginning to provide a more coherent picture of the spectrum of disease caused by mutations in MECP2; and 3) the neurobiologic role of the MECP2 gene in RS as well as in normal development has been greatly clarified with the elaboration of animal models of RS. More recent study of MECP2 in neuronal culture systems humans and rodents has significantly extended our understanding of the role of this gene in neural structure and function.

Conclusion: RS is a unique neurodevelopmental disorder that has emerged as an important beacon for exploring the molecular bases of neuronal function.

Keywords: Rett syndrome, MECP2, mutations, phenotype, genotype, neurobiology