Rett Syndrome: A Genetic Update and Clinical Review Focusing on Comorbidities

Abstract

Rett syndrome (RTT) is a unique neurodevelopmental disorder that primarily affects females resulting in severe cognitive and physical disabilities. Despite the commendable collective efforts of the research community to better understand the genetics and underlying biology of RTT, there is still no cure. However, in the past 50 years, since the first report of RTT, steady progress has been made in the accumulation of clinical and molecular information resulting in the identification of a number of genes associated with RTT and associated phenotypes, improved diagnostic criteria, natural history studies, curation of a number of databases capturing genotypic and phenotypic data, a number of promising clinical trials and exciting novel therapeutic options which are currently being tested in laboratory and clinical settings. This Review focuses on the current knowledge of the clinical aspects of RTT, with particular attention being paid to clinical trials and the comorbidities of the disorder as well as the genetic etiology and the recognition of new diseases genes.

Keywords: CDKL5; FOXG1; MECP2; Neurodevelopment; Rett syndrome.