# Rett Syndrome

> Rett syndrome for NEET-PG Paediatrics, covering regression after normal early infancy, hand-wringing stereotypies, MECP2 mutation and management.

- Canonical URL: https://prepelephant.com/topics/neet-pg/paediatrics/rett-syndrome
- Exam / course: NEET-PG · Subject: Paediatrics
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Nelson Textbook of Pediatrics; Swaiman's Pediatric Neurology
- How to cite: "Rett Syndrome", PrepElephant, https://prepelephant.com/topics/neet-pg/paediatrics/rett-syndrome

## Direct answer

Rett syndrome is an X-linked dominant neurodevelopmental disorder that almost always affects girls and is caused by MECP2 mutations. Girls develop apparently normally for six to eighteen months, then regress with loss of purposeful hand use and speech, and develop hand-wringing stereotypies. Management is supportive and multidisciplinary, with trofinetide licensed for core symptoms in some countries.

## What you must remember

- **Sex and genetics:** nearly all cases occur in girls, usually from de novo MECP2 mutations on the X chromosome, and boys with classic mutations rarely survive infancy.
- **Early course:** development appears normal until about six to eighteen months, after which head growth slows and regression begins.
- **Hand stereotypies:** hand-wringing, clapping or hand-to-mouth movements replace purposeful hand use and persist during waking hours.
- **Gait and breathing:** an ataxic, apraxic gait with later loss of walking, and irregular breathing such as hyperventilation and breath-holding while awake.
- **Other features:** seizures, scoliosis, cold extremities and constipation from autonomic disturbance, and teeth grinding.
- **Contrast with autism:** early social withdrawal can resemble autism, but the regression and hand stereotypies distinguish Rett syndrome.
- **Diagnosis:** clinical criteria are confirmed by MECP2 testing, while CDKL5 and FOXG1 variants produce overlapping but distinct phenotypes.
- **Management:** physiotherapy, speech therapy, seizure control, scoliosis surveillance and nutrition, with trofinetide licensed in some countries for core symptoms.

## Staging the regression

The clinical course of Rett syndrome is commonly described in four stages, summarised below, and staging tells the team which complications to expect next. Stage I is easily missed, because subtle slowing resembles normal infant variation.

| Stage | Approximate age | Key features |
|---|---|---|
| I, early onset | 6 to 18 months | Slowing development, reduced head growth and subtle loss of hand purpose |
| II, rapid regression | 1 to 4 years | Loss of hand skills and speech, hand stereotypies, irritability and breathing irregularity |
| III, plateau | 2 to 10 years | Relative stability, with seizures, scoliosis and ongoing therapy needs |
| IV, late motor decline | After about 10 years | Reduced mobility, wheelchair dependence and progressing scoliosis |

Stage II is the destructive phase, and the regression seen there, with loss of hand skills and speech, is what separates Rett syndrome from a static encephalopathy. Stage IV reflects progressive motor decline, while many girls keep some social engagement and eye contact.

## Where the exam tries to catch you

Rett questions usually test whether you can separate the condition from autism and from other regressive disorders.

- **Trap:** labelling a regressing girl with autistic features as autism and stopping there. — **Correct:** regression after normal early development with hand stereotypies points to Rett syndrome, so MECP2 testing is indicated.
- **Trap:** expecting boys with classic Rett mutations to survive as often as girls. — **Correct:** classic MECP2 mutations are largely lethal in early infancy in males, which explains the female predominance.
- **Trap:** assuming a cure is available. — **Correct:** management is symptomatic and supportive, and trofinetide addresses symptoms rather than the underlying genetic defect.

## Frequently asked questions

### Which gene is mutated in Rett syndrome?
Rett syndrome is caused by mutations in the MECP2 gene on the X chromosome, most often arising de novo. MECP2 encodes a methyl-CpG binding protein that regulates neuronal gene expression.

### What hand movement is typical of Rett syndrome?
The typical hand movement of Rett syndrome is hand-wringing or washing, with the hands held in front of the body and repeated motion replacing purposeful hand use. These stereotypies appear during the regression phase and persist while the child is awake.

### Why does Rett syndrome almost never affect boys?
Rett syndrome almost always affects girls because a classic MECP2 mutation on the single X chromosome in boys is usually lethal in early infancy. Milder male presentations have been described with mosaicism or Klinefelter syndrome.

### Which drug has been licensed for Rett syndrome?
Trofinetide has been licensed for Rett syndrome in some countries, including the United States, to improve core symptoms in girls aged two years and above. It is a symptomatic therapy and does not correct the underlying MECP2 defect.