ConditionChildren's health
Rett Syndrome
Rett syndrome is a rare genetic neurological disorder that almost always affects girls. After about 6 to 18 months of apparently normal development, a child loses spoken words and purposeful hand use, and develops repetitive hand-wringing movements, walking problems and breathing irregularities. It is caused by changes in the MECP2 gene on the X chromosome and is usually not inherited. There is no cure, but therapies, the medicine trofinetide and specialist care help, and many people live into middle age.
Also called: RTT, MECP2-related disorder, classic Rett syndrome, atypical Rett syndrome
At a glance
- What it is
- A neurodevelopmental disorder causing regression of speech, hand use and movement in early childhood.
- Cause
- A new (de novo) change in the MECP2 gene in about 95% of classic cases.
- Who
- Mainly girls, about 1 in 10,000 to 15,000 female births.
- Hallmark signs
- Loss of hand skills, hand-wringing, loss of speech, unsteady walking, breathing irregularities.
- Diagnosis
- Clinical criteria plus genetic testing.
- Treatment
- Trofinetide, seizure medicines, therapies, and management of scoliosis, gut, heart and sleep problems.
When to get help
Call 911 or go to the ER
- A seizure lasting more than 5 minutes, or repeated seizures without recovery: call 911 or your local emergency number
- Fainting, collapse or a very irregular heartbeat (Rett syndrome can affect heart rhythm)
- Choking on food or drink followed by breathing difficulty, fever or cough (possible aspiration pneumonia)
- Blue lips or long pauses in breathing that do not resolve
See a doctor within a day or two
- Severe belly pain, a swollen belly or vomiting (possible gallbladder problems, severe constipation or bowel obstruction)
- Unexplained crying, screaming or distress in a child who cannot communicate pain (check for fractures, reflux, dental pain or constipation)
- Weight loss, refusal to eat or feeding taking much longer than usual
Book a routine appointment
- A toddler who loses words or hand skills she previously had
- Repetitive hand-wringing, clapping or mouthing with slowing development
- Head growth slowing on the growth chart
- A visible curve of the spine
What Rett syndrome is
Rett syndrome is a disorder of brain development and function, not a degenerative disease. The MECP2 gene makes a protein that controls the activity of many other genes in nerve cells, particularly for the maturation of connections (synapses). When the protein does not work, nerve cells form and survive but do not mature and communicate properly.
The condition was first described by Austrian pediatrician Andreas Rett in 1966.
Why it mostly affects girls
MECP2 is on the X chromosome. Girls have two X chromosomes, and in each cell one X is randomly switched off. A girl with an MECP2 change has a mix of cells using the working and non-working copy, which allows survival and explains the wide range of severity. Boys have only one X, so a boy with the same change usually has a severe neonatal encephalopathy and often does not survive infancy. Boys can be affected more mildly if they have an extra X (Klinefelter syndrome), a mosaic change, or a milder variant.
Is it inherited?
In more than 99% of cases, the gene change is new (de novo) and happens in the sperm or egg, so parents do not carry it and the chance of it happening again in another child is very low. Rarely, a mother carries the change with mild or no symptoms because of skewed X inactivation.
Rett syndrome stages
Development typically follows four stages, though the timing varies:
| Stage | Typical age | What happens |
|---|---|---|
| 1. Early onset | 6 to 18 months | Subtle slowing: less eye contact, less interest in toys, low muscle tone, delayed sitting or crawling. Often missed |
| 2. Rapid regression | 1 to 4 years | Loss of spoken words and purposeful hand use over weeks to months; hand-wringing starts; irritability, autism-like features, sleep problems, breathing irregularities, unsteady walking |
| 3. Plateau | Preschool to adulthood | Regression stops. Communication through eye gaze often improves, along with alertness and interest. Seizures and hand movements continue |
| 4. Late motor deterioration | Teens onward | Reduced mobility, muscle weakness, stiffness, curved spine; some stop walking. Thinking, eye gaze and hand skills usually do not decline further |
Symptoms of Rett syndrome
Core features
- loss of purposeful hand skills such as grasping and feeding herself
- repetitive hand movements: wringing, squeezing, clapping, tapping, washing or mouthing, the most recognizable sign
- loss of spoken language
- gait problems: unsteady, wide-based or toe walking, or never learning to walk
Other common features
- breathing irregularities while awake: breath-holding, hyperventilation, air swallowing
- seizures, in most people at some point
- slowing of head growth (acquired microcephaly) and of overall growth
- scoliosis, often progressing in the teen years
- teeth grinding, sleep disturbance and night laughing or screaming
- cold, small, bluish hands and feet
- reduced response to pain
- constipation, reflux, chewing and swallowing difficulty, and air in the gut
- anxiety, mood changes and episodes of agitation
- intense eye gaze, used to communicate
Rett syndrome was once grouped with autism. Autism-like withdrawal is common during regression, but social interest usually returns in the plateau stage.
Diagnosis
Diagnosis uses revised clinical criteria. Classic Rett syndrome requires a period of regression followed by recovery or stabilization, plus all four core features: loss of hand skills, loss of language, gait abnormalities and hand stereotypies. Supportive features include breathing irregularities, bruxism, scoliosis and cold extremities. Atypical Rett syndrome shows some but not all core features.
- Genetic testing: a blood test for MECP2 changes confirms the diagnosis in most cases. A small number of people meet the criteria without a detectable change, and some people with MECP2 changes do not have Rett syndrome.
- Related conditions: disorders caused by CDKL5 and FOXG1 genes were once considered Rett variants but are now recognized as separate conditions.
- Other tests: EEG for seizures, an ECG to check the QT interval, and evaluation of growth, feeding, bones and spine.
Differential diagnoses include autism spectrum disorder, Angelman syndrome, cerebral palsy and metabolic disorders.
Treatment
Medicine
Trofinetide (Daybue), approved by the FDA in 2023 for people aged 2 and older, is the first medicine specifically for Rett syndrome. In clinical trials it modestly improved behavior, communication and overall functioning. Diarrhea and vomiting are common side effects.
Gene therapies and other targeted treatments are in clinical trials.
Managing symptoms
- Seizures: anti-seizure medicines. Some breathing episodes can be mistaken for seizures, so EEG monitoring helps.
- Heart: a yearly ECG to monitor for a long QT interval, and avoidance of medicines that prolong QT. See long QT syndrome.
- Scoliosis: monitoring, bracing, and spinal fusion surgery for severe curves.
- Nutrition and gut: high-calorie diets, treatment of reflux and constipation, and a gastrostomy (feeding tube) if eating is unsafe or too slow.
- Bones: vitamin D, calcium and weight-bearing activity, as fractures are more common.
- Sleep: routines and sometimes melatonin.
- Anxiety and agitation: behavioral support and medicines where needed.
Therapies
- Physical therapy to maintain walking, balance and posture.
- Occupational therapy for hand function, splints to reduce hand-wringing, and seating.
- Speech and communication therapy, especially eye-gaze devices and augmentative communication systems. Many girls and women with Rett syndrome understand far more than they can express.
- Music and hydrotherapy are often enjoyed and can support movement and engagement.
Outlook and life expectancy
Rett syndrome is lifelong, and most people need full-time care. Many live into their 40s, 50s and beyond, especially with good management of nutrition, seizures, breathing and heart rhythm. Sudden unexpected death, sometimes linked to heart rhythm or breathing problems, is more common than in the general population. With modern care, many girls and women attend school, communicate with eye-gaze technology and enjoy family life and activities.
Frequently asked questions
What are the early signs of Rett syndrome?
Early signs between 6 and 18 months are often subtle: low muscle tone, less eye contact, less interest in toys and delayed motor milestones. The more obvious signs follow: losing words and hand skills, repetitive hand-wringing, and slowing head growth.
Can boys have Rett syndrome?
Rarely. Most boys with an MECP2 change have a severe brain disorder from birth and may not survive infancy. Boys with an extra X chromosome or a mosaic or milder gene change can have features of Rett syndrome and live longer.
What is the life expectancy for Rett syndrome?
Many people with Rett syndrome live into middle age and beyond. Survival into the 40s and 50s is common with good care. Risks include breathing problems, pneumonia, seizures and heart rhythm disturbances, which is why regular monitoring is important.
Is Rett syndrome a form of autism?
No. Rett syndrome was once listed with autism spectrum disorders because autism-like withdrawal occurs during regression. It is now recognized as a separate genetic condition. Social interest and eye contact often improve after the regression stage, unlike in autism.
Is there a treatment for Rett syndrome?
There is no cure, but trofinetide was approved by the FDA in 2023 as the first treatment specific to Rett syndrome. Care also includes seizure control, therapies, nutrition support, scoliosis management and communication aids. Gene therapies are being tested.
Sources
This guide was written from current patient and clinical guidance, including:
- National Institute of Neurological Disorders and Stroke: Rett syndrome
- MedlinePlus Genetics: Rett syndrome; MECP2 gene
- Neul JL et al: Rett syndrome, revised diagnostic criteria and nomenclature (Annals of Neurology)
- US Food and Drug Administration: FDA approves first treatment for Rett syndrome (trofinetide)
- International Rett Syndrome Foundation: About Rett syndrome