Rett Syndrome

Rett syndrome is a debilitating neurodevelopmental disorder that affects 1 in 10,000 to 15,000 live female births and rare surviving male births. Children with Rett syndrome show either failure to meet and/or regression of developmental milestones between 6 and 18 months including impairment of cognitive, language, social, motor, and sensory function. The impact of the genetic disorder not only leads to neurological manifestations, including seizures and breathing difficulties but also to psychiatric symptoms including anxiety and depression. Ninety-five to 97% of Rett syndrome cases are caused by loss-of-function mutations in MECP2, which encodes for a transcriptional regulator/chromatin remodeler that plays key roles in brain cell development and maintenance. Advances in genetic technologies since the discovery of MECP2 reveal additional distinct mutations from those that cause Rett syndrome including MECP2 duplication syndrome and other MECP2-related disorders. This chapter first provides an overview of the syndromes and then focuses on the recognition and treatment of neuropsychiatric symptoms.