Rett Syndrome

Rett Syndrome is a rare neurodevelopmental disorder that primarily affects girls and is characterized by early normal development followed by a period of regression. Affected children lose acquired motor and language skills, develop repetitive hand movements, and often experience seizures, breathing irregularities, and cognitive impairment.

Though it shares features with autism spectrum disorder, Rett Syndrome has a distinct genetic cause and clinical course.

It affects approximately 1 in 10,000 to 15,000 live female births worldwide.

Rett Syndrome presents in several forms, depending on severity and mutation type:

• Typical or Classic Rett Syndrome (most common)
• Developmental regression between 6–18 months
• Loss of purposeful hand use, replaced by stereotyped hand wringing or clapping
• Loss of spoken language
• Gait disturbances or inability to walk
• Autonomic dysfunction: irregular breathing, bruxism, cold extremities

Atypical Rett Syndrome, including:

• Congenital variant
• Preserved speech variant
• Early seizure variant

Most cases are caused by mutations in the MECP2 gene on the X chromosome, which plays a critical role in brain development and gene regulation.

As an X-linked dominant disorder, Rett Syndrome primarily affects girls; boys with MECP2 mutations usually have more severe neonatal presentations or do not survive infancy.

MECP2 mutations lead to dysregulation of synaptic function and neural plasticity, contributing to the wide range of neurological symptoms seen in Rett Syndrome.