What is Rett syndrome?

Rett syndrome is a progressive neurodevelopmental disorder that affects a child’s brain development and cognitive ability. Over time, it can cause severe problems with language and communication, lack of coordination and muscle control, involuntary hand movements, and slowed growth.

Rett syndrome almost exclusively affects females, although males can be affected in very rare cases. In the United States, the disorder affects 1 in 10,000 girls by the age of 12.

Babies born with Rett syndrome generally develop normally for the first few months of their lives. They meet typical developmental milestones such as making eye contact, interacting with caregivers, rolling over and grasping objects purposefully. However, between 6 and 18 months old, children with Rett syndrome begin to lose previously acquired skills, lose interest in normal play, and often become increasingly irritable.

As they grow, children with Rett syndrome begin to display increasing problems with communication and control of muscle movement, leading to difficulty with motor activities such as walking. They may develop difficulties with breathing, feeding and swallowing, and can experience seizures and sleep disturbances. Most affected children are diagnosed with an intellectual disability.

The current treatment approach for Rett syndrome focuses on managing symptoms, improving movement and communication, and supporting patients and their families. At this time, there is no cure for the disorder.

Causes of Rett syndrome

Rett syndrome is caused by mutations of the MECP2 gene on the X chromosome, one of the two chromosomes that determine a person’s sex. Girls have two X chromosomes, while boys have one X and one Y. Rett syndrome most often affects girls because they have a second copy of the MECP2 gene that is able to work properly, but boys do not.  However, there are a small number of boys identified with MECP2 mutations, most of whom are very severely affected. 

In the majority of cases, Rett syndrome is not inherited (passed from parent to child). So far, more than 200 mutations of the MECP2 gene have been identified and linked to Rett syndrome.

In normal human development, the MECP2 gene helps create a protein (Methyl-CpG-binding protein 2) that regulates the activity of other genes in the body. When the protein level is altered because of a faulty gene, it causes other genes in the body to malfunction, and ultimately affects normal brain development.

Children with the disorder can present with a wide range of disability and symptoms.  Although this may be influenced by the location, type and severity of the gene mutation, there are likely other factors involved as well. More research is needed to better understand the MECP2 gene and how it affects different body functions.

Signs and symptoms of Rett syndrome

Symptoms of Rett syndrome can vary dramatically from person to person, and include a wide range of disability. Although the genetic change that causes Rett syndrome is present from before birth, in most cases, a child with Rett syndrome will appear to grow and develop normally for the first 6 to 18 months of life before symptoms begin to appear.

Initial Rett syndrome symptoms may include:

• Developmental delays or stagnation
• Loss of eye contact
• Lack of interest in normal play and interactions
• Slowing of head growth, leading to microcephaly, a smaller-than-normal head size for the child’s age and gender
• Increased irritability
• Low muscle tone

As affected children grow, they may lose skills they’ve already learned such as spoken language, the ability to use their hands effectively for activities such as feeding themselves or communication, and basic social interaction. Children with Rett syndrome may begin to show less interest in the people and objects they used to enjoy.

Most children with the disorder begin to exhibit classic Rett syndrome hand movements between 1 and 4 years of age. These can include repetitive squeezing, rubbing, wringing, clapping, and repeated hand-to-mouth movements.

As the disorder progresses, children will find it increasingly difficult to control their muscles to perform coordinated motor movements. This neurological condition is also called apraxia or dyspraxia, and it can cause many related issues, like some of those explained here. Some children with Rett syndrome will learn to walk and maintain this ability; others may eventually lose this skill, while some may never walk independently.

Additional symptoms of Rett syndrome may include:

• Childhood apraxia of speech, in which a child’s brain has difficulty coordinating the muscle movements needed to form syllables and words
• Involuntary muscle contractions that cause repetitive movements (dystonia)
• Muscle weakness, joint contractures and spasticity
• Scoliosis
• Symptoms similar to those seen in Parkinson’s disease, such as tremors, rigidity and decreased facial expressions
• Sleep disturbances, including difficulty falling asleep or staying asleep
• Disordered breathing, which includes breathing too fast or slow, breath holding, and swallowing air
• Feeding and swallowing difficulties
• Gastrointestinal issues including reflux and constipation
• Seizures
• Panic attacks or anxiety
• Autism-like features
• Poor growth and difficulty gaining weight

After a child’s initial regression due to Rett’s syndrome, development tends to stabilize in most girls. Some skills (i.e. lack of interest or communication) may show improvements, while others (i.e. motor skills) may remain impaired or gradually progress. Other symptoms, such as breathing abnormalities or seizures, may come and go over time.

Despite their many challenges, children with Rett syndrome each have their own unique personalities, with likes and dislikes, similar to typically developing children.

Testing and diagnosis of Rett syndrome

Diagnostic evaluation of Rett syndrome usually begins with the identification of characteristic symptoms of the disorder, along with a comprehensive medical history and physical examination.

At Children’s Hospital of Philadelphia (CHOP), clinical experts use a variety of diagnostic tests to confirm a Rett syndrome diagnosis and identify symptoms that may require treatment. Tests may include:

• Genetic testing to identify mutations of the MECP2 gene and confirm the clinical diagnosis
• Neurological testing such as an electroencephalogram (EEG), which evaluates the electrical activity in the brain and can detect seizure disorders
• Imaging tests such as an X-ray or MRI to examine bones, organs and other structures in the body
• Pulmonary function tests and cardiac function tests including  electrocardiography (EKG) to determine how well the child’s lungs and heart are working

Depending on your child’s symptoms, additional evaluations may be needed to better understand any feeding and swallowing problems, gastrointestinal issues or other medical problems your child may be experiencing.

Treatment for Rett syndrome

Currently, there is no cure for Rett syndrome. Treatment for children with the disorder is complex and varied, and must be customized to address your child’s specific needs.

At CHOP, a team of specialists — including neurologists, geneticists or genetic counselors, pediatricians, gastroenterologists, orthopedists, physiatrists, speech therapists, physical and occupational therapists, nutritionists and other healthcare professionals — work together to develop a comprehensive treatment plan for your child.

The International Rett Syndrome Foundation has designated CHOP as one of 15 partner clinics in its Center of Excellence network.

Our goal is to provide your child with early developmental intervention that will help them reach their potential.

Treatment for children with Rett syndrome often includes:

• Occupational and physical therapy, including the seating clinic and adaptive equipment evaluations
• Speech therapy to maximize verbal communication and to consider augmentative or alternative forms of communication.
• Rehabilitative and behavior therapy
• Special educational support
• Psychosocial support for the child and family, including the Division of Neurology’s dedicated social workers, access to support groups and programs such as Sibshops, and connection to national support organizations
• Nutritional support in the form of supplements, tube feedings, or specialized diets
• Medications to treat specific symptoms such as seizures, spasticity and muscle rigidity, GI abnormalities, breathing problems and others

Children with Rett syndrome are also at increased risk of developing scoliosis and cardiac arrhythmia – both of which may require additional treatment.

At Children’s Hospital, we continue to adjust our approach to care for children with Rett syndrome based on the latest research findings and treatment approaches.

Rett syndrome Research

Researchers at CHOP are working to better understand the MECP2 gene mutations that cause Rett syndrome. Our goal is to develop improved treatments to address specific symptoms, and to improve the quality of life for children with this disorder.

CHOP is also a participating center for the Rett Syndrome, MECP2 Duplication, and Rett-related Disorders Natural History Study. The goal of this study is to gather as much data as possible about children and adults with Rett syndrome in order to stimulate more clinical research and better prepare us for future clinical trials. Learn more about the Rett-related Disorders Natural History Study.

Outlook

The outlook for children with Rett syndrome is varied and largely depends on the progression and severity of symptoms that are present in each individual.

Although children with Rett syndrome will need help with most daily activities, many can learn some independent skills, such as feeding or toileting with assistance. While verbal communication is typically limited, many girls can learn to communicate in other ways, such as by using augmentative communication devices.

With supportive care at home and in their community, people with Rett syndrome can live into middle age. However, because of related conditions and health complications, people with Rett syndrome generally have a shorter life expectancy than the average population.

The majority of individuals with Rett syndrome are not able to live independently because of their significant needs, and will remain with their families or in another setting where they can receive appropriate care into adulthood. Therefore, it is important to maintain a dialogue with your child’s healthcare providers and to coordinate a plan for transitioning from pediatric to adult care. Despite these limitations, individuals with Rett syndrome can continue to learn and be engaging members of their families and communities.