title: Clinical and biological progress over 50 years in Rett syndrome.
abstract: In the 50 years since Andreas Rett first described the syndrome that came to bear his name, and is now known to be caused by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, a compelling blend of astute clinical observations and clinical and laboratory research has substantially enhanced our understanding of this rare disorder. Here, we document the contributions of the early pioneers in Rett syndrome (RTT) research, and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation, and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, considering the lessons learned from both cell and animal models, and how they might inform future clinical trials. With a focus on the core criteria, we examine the relationships between genotype and clinical severity. We review current knowledge about the many comorbidities that occur in RTT, and how genotype may modify their presentation. We also acknowledge the important drivers that are accelerating this research programme, including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we highlight the major milestones since 1966, and what they mean for the day-to-day lives of individuals with RTT and their families.
authors.affiliation: Telethon Kids Institute, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Leonard
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Cobb
authors.affiliation: Telethon Kids Institute, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Downs
mesh_terms: D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D015518:Rett Syndrome