Rett syndrome: from recognition to diagnosis to intervention

Abstract

Rett syndrome is a relatively rare neurodevelopmental disorder (incidence: approximately one out of 10,000 female births) that reached worldwide prominence in the early 1980s. Owing to its overwhelming predominance in females, Rett syndrome was regarded as a genetic disorder. However, its occurrence is sporadic, with a recurrence risk well below 0.5%. In 1999, confirmation was provided by the demonstration of mutations in the MECP2 gene. At present, more than 95% of females who fulfill consensus criteria for Rett syndrome have a mutation in this gene. Over the past 25 years, understanding of the clinical features and natural history of this unique neurodevelopmental disorder has evolved dramatically. However, large segments of healthcare professionals and the general public still remain relatively uninformed. This review details the clinical picture of Rett syndrome and the diagnostic strategies required, explores the critical medical issues and recent advances in molecular neurobiology, provides an overview of intervention strategies that have been developed to date and sets the stage for future treatment trials as novel, and potentially effective, pharmacologic or molecular interventions become available.