Learning Objective: By the end of this session, students should be able to describe the genetic basis, clinical progression, and characteristic clinical manifestations of Rett syndrome, and differentiate it from other neurodevelopmental disorders.
Overview
| Feature | Description |
|---|---|
| Genetics | Sporadic disorder caused by a de novo mutation in the MECP2 gene on the X chromosome. |
| Epidemiology | Occurs almost exclusively in females; typically embryonically lethal in males. |
| Pathophysiology | MECP2 encodes a methyl-CpG–binding protein required for neuronal maturation and synaptic function. Mutation causes abnormal neuronal development and synaptic dysfunction. |
| Clinical Course | Normal development for 6–18 months → followed by regression (“Rett-turn”) in motor, verbal, and cognitive abilities. |
| Key Clinical Features | – Loss of purposeful hand use → stereotypic hand-wringing 🤲 – Ataxia, seizures, intellectual disability – Scoliosis and growth retardation |
| Inheritance Pattern | X-linked dominant, usually de novo (sporadic). |
| Mnemonic | RETT = Regression, Epilepsy, Twisting hands, Toddler onset. |
Clinical Pearl
A girl who develops normally for the first year but then loses speech and hand coordination with repetitive hand-wringing should raise strong suspicion for Rett syndrome.
