Rett syndrome overview

Last updated Sept. 18, 2025, by Marisa Wexler, MS
Fact-checked by José Lopes, PhD

Rett syndrome is a rare genetic disorder that primarily affects girls, causing abnormalities in brain development. The condition affects about 1 out of every 10,000 females, and it is marked by developmental regression, motor skill loss, and communication difficulties.

Babies with Rett syndrome usually show no signs of abnormal development for the first few months of life. Then, around 6 to 18 months, normal development stalls. This is followed by a period of regression where previously-learned skills are rapidly lost. The regression then ends, with cognitive and communication skills stabilizing or even improving, though patients often experience new motor complications as they enter adolescence and adulthood.

There is no cure for Rett, though treatments are available. Most people with Rett will require regular care throughout their lives. Life expectancy in Rett syndrome depends on the type of mutation a patient has, but many people with the condition live into their 40s and beyond.

Causes and risk factors

In more than 95% of cases, Rett syndrome is caused by mutations in a gene called MECP2. This gene provides instructions to make a protein called MeCP2. It is thought that Rett occurs because MECP2 mutations lead to reduced activity of the MeCP2 protein, which disrupts normal brain development and the communication between brain cells to ultimately cause the symptoms of Rett syndrome.

The MECP2 gene is located on the X chromosome, which is one of the two sex-determining chromosomes. Females have two X chromosomes, and males have one X and one Y. Girls with Rett syndrome have one X chromosome with a mutant copy of the MECP2 gene, and the other with a healthy copy that can partly compensate for the mutated gene.

Rett syndrome can also affect boys, but this is very rare. Boys with a MECP2 mutation more often develop severe neonatal-onset encephalopathy, a condition marked by profound abnormalities at birth.

In about 99% of cases, MECP2 mutations occur spontaneously in sperm or egg cells, or during the growth of cells in early embryonic development, rather than being inherited from either biological parent. Therefore, if two parents have one child with Rett syndrome, the odds of having a second child with the disorder are minimal. There are exceptions, however, and genetic testing is available to identify people who may be at higher risk of passing a MECP2 mutation to their offspring.

Other genes, namely CDKL5 and FOXG1, have been shown to cause certain types of atypical Rett syndrome, although there are experts considering these as separate diseases rather than subtypes of Rett syndrome. Other Rett syndrome causes may exist but have not yet been discovered.

Common symptoms

Babies with Rett syndrome usually do not show any obvious symptoms in early infancy. The first early signs generally do not appear until 6 to 18 months of age. Early Rett syndrome symptoms may include:

delays in reaching motor milestones like crawling and standing
reduced eye contact
lack of interest in toys
low muscle tone and difficulty feeding.

Rett patients will then enter a period of rapid regression, marked by symptoms such as:

loss of voluntary hand movements and the appearance of repetitive, abnormal hand movements
loss of spoken language
behavioral issues and lack of interest in social interaction.

After the period of rapid regression, patients will generally stabilize and may even gain some new skills over time, though most will continue to have substantial challenges with communication and motor skills. Many Rett patients will also experience other symptoms including:

seizures
digestive complaints
sleep problems
sideways abnormal curvature of the spine (scoliosis).

Types and stages of Rett syndrome

Most people with Rett syndrome have what’s called the classic form of the disease, and they meet all the main diagnostic criteria. In these patients, there are four Rett syndrome stages:

Stage 1: Following a period of normal development in infancy, at about 6 to 18 months of age, development stalls. This lasts for a few months to a year.
Stage 2: A period of rapid regression follows, where children quickly lose motor and social skills that they had previously acquired. This typically begins between 1 and 4 years of age, and lasts weeks or months.
Stage 3: Starting around preschool or early school age, development stabilizes. Patients maintain their social and motor skills, and may pick up some new skills or re-acquire skills that had been lost. This can last for many years.
Stage 4: Usually after age 10, cognitive and social functioning remains stable, but new motor problems may start to develop.

Not everyone with Rett syndrome will progress through each of these stages in the outlined timeframe, however. This is especially true of people with atypical forms of Rett syndrome who show many of the characteristics that define the disease, but do not meet all the diagnostic criteria. Compared with the classic disease, five atypical Rett syndrome types have been described:

the early-onset seizure (Hanefeld) variant, which is marked by seizures that start in infancy
the congenital (Rolando) variant, which is marked by earlier developmental delays
the forme fruste variant, which is characterized by milder symptoms
the late childhood regression form, which is characterized by a later and more gradual loss of skills
the preserved speech (Zappella) variant, which is marked by a more pronounced recovery in skills.

Diagnosis

Rett syndrome is a clinical diagnosis, meaning that the diagnosis is established by an expert reviewing a patient’s symptoms to see if they meet all the diagnostic criteria for Rett syndrome and ruling out other possible disorders.

To establish a diagnosis of classic Rett syndrome, patients must experience a period of regression followed by stabilization or recovery, as well as meet four main criteria:

a loss of voluntary hand movements, such as grasping and reaching
development of atypical, repetitive hand movements, such as squeezing, clapping, and tapping
a loss of speaking ability
problems walking, including abnormal gait and being unable to walk.

For an atypical Rett syndrome diagnosis, patients must show a pattern of regression and stabilization and meet at least two of the four main criteria for classic Rett syndrome. To confirm this atypical diagnosis, patients must also meet at least five of 11 supportive criteria:

breathing irregularities while awake
teeth grinding while awake
sleep problems
abnormal muscle tone
disturbances in blood flow
scoliosis or kyphosis (an excessive forward curve of the spine)
slow growth
small and cold hands and feet
unexplained laughing or screaming
reduced response to pain
intense eye communication.

Diagnosing Rett also requires patients to meet exclusion criteria, which includes ruling out injury or infections that can cause brain damage and neurological problems, and having no obvious signs of abnormal development in the first six months of life.

Genetic testing may help to confirm the diagnosis, but not everyone with a MECP2 gene mutation develops the known clinical features of Rett.

Treatment and management

Rett syndrome treatment can help ease symptoms and improve quality of life for patients and their families.

In the U.S., the only approved therapy for Rett syndrome is the daily oral medication Daybue (trofinetide), which is indicated for patients 2 years and older. Clinical trials have shown that Daybue led to continual improvements over years in children and young adults with Rett, with benefits noted in communication and other relevant issues.

Apart from Daybue, a variety of other medications may be used to manage specific symptoms of Rett. These may include:

antiepileptic drugs to manage seizures
medicines like laxatives and acid reducers for digestive issues
medications for mental health issues, such as anxiety and depression
treatments to support sleep, mobility, breathing, and heart health.

People with Rett syndrome commonly benefit from other types of supportive care such as physiotherapy and occupational therapy. The use of aids and adaptive devices can help Rett patients and their families navigate day-to-day life and manage disease complications.

Outlook and living with Rett syndrome

The majority of Rett syndrome patients survive into adulthood, and life expectancy for most classic Rett cases is in the 40s. Most people with Rett syndrome will require long-term care and help with day-to-day activities throughout their lives, though some individuals may be able to do certain activities like eating or using the toilet with a degree of independence.

Regular and multidisciplinary medical monitoring, along with supportive care, adaptive equipment, and home modifications, can help patients and their families maximize their quality of life.

Living with Rett syndrome can be challenging, but no one needs to go through life on their own. Various organizations offer support for Rett syndrome families, including:

Rett Syndrome News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.