Rett

Rett syndrome is a rare neurodevelopmental disorder that primarily affects girls and is caused by mutations in the MECP2 gene on the X chromosome. Most cases arise spontaneously rather than being inherited. The condition typically becomes evident after a period of normal development, usually between six and 18 months, followed by regression.

Common features include loss of purposeful hand use with development of repetitive hand movements, such as wringing or washing, a decline in spoken language, reduced social engagement, motor abnormalities such as ataxia or apraxia, and gait disturbances. Other signs can include breathing irregularities, scoliosis, sleep disturbances, feeding problems, seizures, and increasingly diminished motor coordination.

Rett syndrome is caused mainly by de novo mutations in MECP2, a gene essential for brain development. It is X-linked dominant; because affected girls have two X chromosomes, the normal one partially compensates, while most affected males have more severe illness and lower survival. Prevalence is about 1 in 10,000 to 15,000 female births. Some individuals with Rett-like features have mutations in other genes, such as CDKL5 or FOXG1.

Diagnosis is based on clinical criteria supported by genetic testing for MECP2 mutations. There is no cure, and treatment focuses on multidisciplinary management: physical, occupational, and speech therapy; nutritional support; management of seizures and respiratory and orthopedic complications; and educational and psychosocial support. Life expectancy varies widely and depends on severity and respiratory health.

First described by Dr. Andreas Rett in 1966 and recognized as a distinct syndrome in the 1980s, Rett syndrome has become a key example of a genetic neurodevelopmental disorder. Research continues into disease mechanisms and potential therapies, including symptomatic treatments and experimental gene-based strategies, though no disease-modifying therapy is currently approved.