Rett syndrome

Rett syndrome (RTT) is a severe neurodevelopmental disorder that predominantly affects females. It is caused in the vast majority of cases by mutations in the MECP2 gene located on the X chromosome. The condition was first described by Austrian physician Andreas Rett in 1966 and is one of the most common genetic causes of severe intellectual disability in females. Rett syndrome is characterized by a period of apparently normal early development during the first 6 to 18 months of life, followed by a regression phase in which affected children lose previously acquired purposeful hand skills and spoken language. A hallmark feature is the development of repetitive stereotypic hand movements, often described as hand-wringing, hand-washing, or hand-mouthing movements. The disorder primarily affects the nervous system but has multisystem involvement. Key clinical features include progressive loss of motor function, gait abnormalities (including ataxia and apraxia), acquired microcephaly (deceleration of head growth), breathing irregularities such as hyperventilation and breath-holding episodes, seizures (affecting up to 80% of patients), autonomic dysfunction, scoliosis, and growth retardation. Many individuals also experience sleep disturbances, bruxism (teeth grinding), and episodes of inconsolable crying or screaming. Cardiac abnormalities, including prolonged QT interval, have been documented and require monitoring. The clinical course is typically divided into four stages: early onset stagnation, rapid developmental regression, a pseudo-stationary period, and late motor deterioration. There is currently no cure for Rett syndrome, but management is multidisciplinary and supportive. Treatment focuses on managing seizures with antiepileptic medications, physical and occupational therapy to maintain mobility and hand function, speech therapy including augmentative communication strategies, nutritional support, and monitoring for scoliosis and cardiac complications. In 2023, trofinetide (Daybue) became the first FDA-approved treatment specifically for Rett syndrome in adults and children aged 2 years and older, representing a significant advance in the treatment landscape. Ongoing research into gene therapy and other targeted approaches offers hope for future disease-modifying treatments.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Rett syndrome