An Overview of Rett Syndrome

Rett syndrome (RTT) is a neurological disorder that is estimated to affect one in every 10,000 live female births -worldwide. In this chapter we discuss the hallmarks of RTT, as well as inheritance of the disease, its diagnostic -testing, evolution, variants, and end of life comorbidities. We describe the consequences of loss-of-function mutations in the gene encoding the transcription factor methyl-CpG binding protein 2 (MeCP2) in RTT, as well as discuss normal and abnormal MeCP2 gene products, genotype-phenotype correlations, and the search for MeCP2 gene -targets. Finally, we provide an overview of current literature regarding pathology in human RTT subjects, MeCP2-based mouse models, alterations in brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 -(IGF-1) levels in RTT individuals and in MeCP2-based mouse models, as well as recent progress in the search for rational therapeutic interventions.