atypical Rett syndrome

Atypical Rett syndrome is a neurodevelopmental disorder that presents with features similar to classic Rett syndrome but without fulfilling all its diagnostic criteria. This condition primarily affects the central nervous system, and affected children may show signs of impaired cognitive and developmental functions. Pathogenic variants in FOXG1 and CDKL5, two genes important for brain development, are associated with the disorder. It is considered uncommon, affecting roughly 1 to 9 individuals per 100,000 people.

After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, including a decline in purposeful hand use and other cognitive functions. Parents often notice that milestones such as speech, social interaction, or motor coordination are not sustained, leading to a diagnosis. The condition is characterized by significant neurological involvement, with challenges in cognitive, developmental, and behavioral domains. Not all individuals experience all features, and severity varies considerably.

Atypical Rett syndrome is associated with pathogenic variants in the FOXG1 and CDKL5 genes. These genes encode proteins that play critical roles in brain development and regulation of neuronal function. Disruptions in their function are believed to interfere with normal neurodevelopment, contributing to the clinical features observed in this disorder. Inheritance information is not clearly established, and families are encouraged to seek genetic counseling to explore these aspects further.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual. A multidisciplinary team typically addresses motor, communication, and behavioral challenges through therapies such as physical, occupational, and speech therapy. Genetic counseling is recommended to help families understand the genetic aspects of atypical Rett syndrome and provide guidance for family planning. Management strategies are regularly reviewed as research progresses and care standards evolve.

Atypical Rett syndrome is a lifelong neurodevelopmental condition characterized by an initial regression followed by a period of relative stabilization and, in some individuals, later motor decline. Outcomes vary widely between individuals, with improvements in quality of life often seen with modern supportive care and early intervention. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition to explore long-term care options.

Clinical trials are underway exploring new treatment approaches for atypical Rett syndrome. Although no treatments are specifically approved for this condition, ongoing research is evaluating additional therapies under investigation. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.