Learning Objectives
- Identify the genetic basis of Rett syndrome and its inheritance pattern.
- Recognize the classic clinical timeline and “regression” phase.
- Distinguish pathognomonic physical signs such as hand-wringing.
1. Genetics & Epidemiology
Rett syndrome is a neurodevelopmental disorder that follows a unique X-linked pattern.
- The Mutation: Caused by a de novo mutation of the MECP2 gene on the X chromosome.
- Gender Specificity: Seen almost exclusively in females. In males, the mutation is typically embryonically lethal.
- Occurrence: Usually sporadic, meaning it is not typically inherited from the parents but occurs as a fresh mutation in the sperm or egg.
2. Clinical Progression (“The Regress”)
A hallmark of Rett syndrome is the specific timing of symptom onset, often referred to by the mnemonic “Ret-turn” to signify the reversal of progress.
- Initial Development: Infants typically appear normal for the first 6–18 months of life.
- Regression: Between 1 and 4 years of age, there is a sudden loss of previously acquired motor, verbal, and cognitive skills.
3. Classic Signs & Symptoms
The USMLE frequently tests the specific physical manifestations of this syndrome:
| Category | Clinical Findings |
|---|---|
| Behavioral | Stereotypic hand-wringing (often looks like washing hands). |
| Neurological | Ataxia, seizures, and microcephaly. |
| Skeletal | Progressive scoliosis. |
Activity