Rett syndrome

Rett syndrome is a rare genetic neurological and developmental disorder that affects the way the brain develops. This disorder causes a progressive loss of motor skills and language. Rett syndrome primarily affects females.

Most babies with Rett syndrome seem to develop as expected for the first six months of life. These babies then lose skills they previously had — such as the ability to crawl, walk, communicate or use their hands.

Over time, children with Rett syndrome have increasing problems with the use of muscles that control movement, coordination and communication. Rett syndrome can also cause seizures and intellectual disabilities. Unusual hand movements, such as repetitive rubbing or clapping, replace purposeful hand use.

Although there's no cure for Rett syndrome, potential treatments are being studied. Current treatment focuses on improving movement and communication, treating seizures, and providing care and support for children and adults with Rett syndrome and their families.

Babies with Rett syndrome usually are born after an uncomplicated pregnancy and delivery. Most infants with Rett syndrome seem to grow and behave as expected for the first six months. After that, signs and symptoms start to appear.

The most pronounced changes generally occur at 12 to 18 months of age, over a period of weeks or months. Symptoms and their severity vary greatly from child to child.

The main signs and symptoms include:

• Slowed growth. Brain growth slows after birth. Smaller than usual head size (microcephaly) is sometimes the first sign that a child has Rett syndrome. As children get older, there is delayed growth in other parts of the body.
• Loss of movement and coordination abilities. The first signs often include reduced hand control and a decreasing ability to crawl or walk. At first, this loss of abilities occurs rapidly, and then it continues more gradually. Eventually muscles become weak or stiff, with unusual movement and positioning.
• Loss of communication abilities. Children with Rett syndrome typically begin to lose the ability to speak, to make eye contact and to communicate in other ways. They may become disinterested in other people, toys and their surroundings. Some children have rapid changes, such as a sudden loss of language. Over time, children may gradually regain eye contact and develop nonverbal communication skills.
• Unusual hand movements. Children with Rett syndrome usually develop repetitive, purposeless hand movements, which differ from child to child. Hand movements may include hand-wringing, squeezing, clapping, tapping or rubbing.

Other signs and symptoms can include:

• Unusual eye movements. Children with Rett syndrome tend to have unusual eye movements, such as intense staring, blinking, crossed eyes or closing one eye at a time.
• Breathing problems. These include breath holding, rapid breathing (hyperventilation), forcefully blowing out air or saliva, and swallowing air. These problems tend to occur during waking hours. Other breathing disturbances such as shallow breathing or short periods of stopping breathing (apnea) can occur during sleep.
• Irritability and crying. Children with Rett syndrome may become increasingly agitated and irritable as they get older. Periods of crying or screaming may begin suddenly, for no apparent reason, and last for hours. Some children may experience fears and anxiety.
• Other unusual behaviors. These may include, for example, sudden, odd facial expressions and long bouts of laughter, hand licking, and grasping of hair or clothing.
• Intellectual disabilities. Loss of skills may be connected to losing the ability to think, understand and learn.
• Seizures. Most people who have Rett syndrome experience seizures at some time during their lives. Multiple seizure types may occur and are associated with changes on an electroencephalogram (EEG).
• Sideways curvature of the spine (scoliosis). Scoliosis is common with Rett syndrome. It typically begins between 8 and 11 years of age and progresses with age. Surgery may be required if the curvature is severe.
• Irregular heartbeat. This is a life-threatening problem for many children and adults with Rett syndrome and can result in sudden death.
• Sleep disturbances. Problems with sleep patterns can include irregular sleep times, falling asleep during the day and being awake at night, or waking in the night with crying or screaming.
• Other symptoms. A variety of other symptoms can occur, such as a decreased response to pain; small hands and feet that are usually cold; problems with chewing and swallowing; problems with bowel function; and teeth grinding.

Stages of Rett syndrome

Rett syndrome is commonly divided into four stages:

• Stage 1: Early onset. Signs and symptoms are subtle and easily overlooked during the first stage, which starts between 6 and 18 months of age. Stage 1 can last for a few months or a year. Babies in this stage may show less eye contact and start to lose interest in toys. They may also have delays in sitting or crawling.
• Stage 2: Rapid deterioration. Starting between 1 and 4 years of age, children lose the ability to perform skills they previously had. This loss can be rapid or more gradual, occurring over weeks or months. Symptoms of Rett syndrome occur, such as slowed head growth, abnormal hand movements, hyperventilating, screaming or crying for no apparent reason, problems with movement and coordination, and a loss of social interaction and communication.
• Stage 3: Plateau. The third stage usually begins between the ages of 2 and 10 years, and it can last for many years. Although problems with movement continue, behavior may slightly improve, with less crying and irritability, and there may be some improvement in hand use and communication. Seizures may begin in this stage and generally don't occur before the age of 2.
• Stage 4: Late motor deterioration. This stage usually begins after the age of 10 and can last for years or decades. It's marked by reduced mobility, muscle weakness, joint contractures and scoliosis. Understanding, communication and hand skills generally remain stable or improve slightly, and seizures may occur less often.

Signs and symptoms of Rett syndrome can be subtle in the early stages. See your child's health care provider right away if you begin to notice physical problems or changes in behavior after what appears to be typical development. Problems or changes may include:

• Slowed growth of your child's head or other parts of the body
• Decreased coordination or mobility
• Repetitive hand movements
• Decreasing eye contact or loss of interest in usual play
• Delayed language development or loss of previous language abilities
• Any clear loss of previously gained milestones or skills

Rett syndrome is a rare genetic disorder. Classic Rett syndrome, as well as several variants (atypical Rett syndrome) with milder or more-severe symptoms, occur based on several specific genetic changes (mutations).

The genetic changes that cause Rett syndrome occur randomly, usually in the MECP2 gene. Very few cases of this genetic disorder are inherited. The genetic changes appear to result in problems with the protein production critical for brain development. However, the exact cause is not fully understood and is still being studied.

Rett syndrome in males

Because males have a different chromosome combination from females, males who have the genetic changes that cause Rett syndrome are affected in devastating ways. Most of them die before birth or in early infancy.

A very small number of males have a different genetic change that results in a less destructive form of Rett syndrome. Similar to females with Rett syndrome, these males are likely to live to adulthood, but they're still at risk of a number of intellectual and developmental problems.

Rett syndrome is rare. The genetic changes known to cause the disease are random, and no risk factors have been identified. In a very small number of cases, inherited factors — for instance, having close family members with Rett syndrome — may play a role.

Complications of Rett syndrome include:

• Sleep problems that cause significant sleep disruption to the person with Rett syndrome and family members.
• Difficulty eating, leading to poor nutrition and delayed growth.
• Bowel and bladder problems, such as constipation, gastroesophageal reflux disease (GERD), bowel or urinary incontinence, and gallbladder disease.
• Pain that may accompany problems such as gastrointestinal issues or bone fractures.
• Muscle, bone and joint problems.
• Anxiety and problem behavior that may hinder social functioning.
• Needing lifelong care and assistance with activities of daily living.
• Shortened life span. Although most people with Rett syndrome live into adulthood, they may not live as long as the average person because of heart problems and other health complications.

There's no known way to prevent Rett syndrome. In most cases, the genetic changes that cause the disorder occur spontaneously. Even so, if you have a child or other family member with Rett syndrome, you may want to ask your health care provider about genetic testing and genetic counseling.

Diagnosing Rett syndrome involves careful observation of your child's growth and development and answering questions about medical and family history. The diagnosis is usually considered when slowing of head growth is noticed or loss of skills or developmental milestones occurs.

For a diagnosis of Rett syndrome, other conditions with similar symptoms must be ruled out.

Evaluating other causes for the symptoms

Because Rett syndrome is rare, your child may have certain tests to determine whether other conditions are causing some of the same symptoms as Rett syndrome. Some of these conditions include:

• Other genetic disorders
• Autism spectrum disorder
• Cerebral palsy
• Hearing or vision problems
• Metabolic disorders, such as phenylketonuria (PKU)
• Disorders that cause the brain or body to break down (degenerative disorders)
• Brain disorders caused by trauma or infection
• Brain damage before birth (prenatal)

What tests your child needs depends on specific signs and symptoms. Tests may include:

• Blood tests
• Urine tests
• Imaging tests such as magnetic resonance imaging (MRI) or computerized tomography (CT) scans
• Hearing tests
• Eye and vision exams
• Brain activity tests (electroencephalograms, also called EEGs)

Core symptoms

Diagnosis of classic Rett syndrome includes these core symptoms, which may start to show up anytime from 6 to 18 months of age:

• Partial or complete loss of purposeful hand skills
• Partial or complete loss of spoken language
• Walking problems, such as difficulty walking or not being able to walk
• Repetitive purposeless hand movements, such as hand-wringing, squeezing, clapping or tapping, putting hands in the mouth, or washing and rubbing movements

Additional symptoms that typically occur with Rett syndrome can support the diagnosis.

Guidelines for diagnosis of atypical Rett syndrome may vary slightly, but the symptoms are the same, with varying degrees of severity.

Genetic testing

If your child's health care provider suspects Rett syndrome after evaluation, genetic testing (DNA analysis) may be needed to confirm the diagnosis. The test requires drawing a small amount of blood from a vein in your child's arm. The blood is then sent to a lab, where the DNA is examined for clues about the cause and severity of the disorder. Testing for changes in the MEPC2 gene confirms the diagnosis. Genetic counseling can help you understand gene changes and their effects.

Although there is no cure for Rett syndrome, treatments address symptoms and provide support. These may improve the potential for movement, communication and social participation. The need for treatment and support doesn't end as children become older — it's usually necessary throughout life. Treating Rett syndrome requires a team approach.

Treatments that can help children and adults with Rett syndrome include:

• Regular medical care. Management of symptoms and health problems may require a multispecialty team. Regular monitoring of physical changes such as scoliosis, gastrointestinal (GI) issues and heart problems is needed.
• Medications. Though medications can't cure Rett syndrome, they may help control some signs and symptoms that are part of the disorder. Medications may help with seizures, muscle stiffness, or problems with breathing, sleep, the GI) tract or the heart.
• Physical therapy. Physical therapy and the use of braces or casts can help children who have scoliosis or require hand or joint support. In some cases, physical therapy can also help maintain movement, create a proper sitting position, and improve walking skills, balance and flexibility. Assistive devices such as a walker or wheelchair may be helpful.
• Occupational therapy. Occupational therapy may improve purposeful use of the hands for activities such as dressing and feeding. If repetitive arm and hand movements are a problem, splints that restrict elbow or wrist motion may be helpful.
• Speech-language therapy. Speech-language therapy can help improve a child's life by teaching nonverbal ways of communicating and helping with social interaction.
• Nutritional support. Proper nutrition is extremely important for healthy growth and for improved mental, physical and social abilities. A high-calorie, well-balanced diet may be recommended. Feeding strategies to prevent choking or vomiting are important. Some children and adults may need to be fed through a tube placed directly into the stomach (gastrostomy).
• Behavioral intervention. Practicing and developing good sleep habits may be helpful for sleep disturbances. Therapies may help improve problem behaviors.
• Support services. Early intervention programs and school, social and job-training services may help with integration into school, work and social activities. Special adaptations may make participation possible.

A few examples of complementary therapies that have been tried in children with Rett syndrome include:

• Music therapy
• Massage therapy
• Hydrotherapy, which involves swimming or moving in water
• Animal-assisted therapy, such as therapeutic horseback riding
• Adapted sports and recreational activities

Although there's relatively little evidence that these approaches are effective, they may offer opportunities for increased movement and social and recreational enrichment.

If you think alternative or complementary therapies might help your child, talk to your health care provider or therapist. Discuss the possible benefits and risks and how the approach might fit into the medical treatment plan.

Children and adults with Rett syndrome need help with most daily tasks, such as eating, walking and using the bathroom. This constant care and disturbed sleep can be exhausting and stressful for families and can impact the health and well-being of family members.

To better cope with the challenges:

• Find ways to relieve stress. It's natural to feel overwhelmed at times. Talk about your problems with a trusted friend or family member to help relieve your stress. Take some time for yourself and do something that you enjoy so you can relax.
• Arrange for outside help. If you care for your child at home, seek the help of outside caregivers who can give you a break from time to time. Or you may consider residential care at some point, especially when your child becomes an adult.
• Connect with others. Getting to know other families facing problems similar to yours can help you feel less alone. Look for online support and information from organizations such as the International Rett Syndrome Foundation.

Your child's health care provider will look for developmental problems at regular checkups. If your child shows any signs or symptoms of Rett syndrome, you may be referred to a pediatric neurologist or developmental pediatrician for testing and diagnosis.

Here's some information to help you get ready for your child's appointment. If possible, bring a family member or friend with you. A trusted companion can help you remember information and provide emotional support.

What you can do

Before your appointment, make a list of:

• Any unusual behavior or other signs. Your health care provider will examine your child carefully and check for slowed growth and development, but your daily observations are very important.
• Any medications that your child takes. Include any vitamins, supplements, herbs and nonprescription medicines, and their dosages.
• Questions to ask your child's health care provider. Be sure to ask questions when you don't understand something.

Questions to ask might include:

• Why do you think my child does (or doesn't) have Rett syndrome?
• Is there a way to confirm the diagnosis?
• What are other possible causes of my child's symptoms?
• If my child does have Rett syndrome, is there a way to tell how severe it is?
• What changes can I expect to see in my child over time?
• Can I take care of my child at home, or will I need to look for outside care or additional in-home support?
• What kind of special therapies do children with Rett syndrome need?
• How much and what kinds of regular medical care will my child need?
• What kind of support is available to families of children with Rett syndrome?
• How can I learn more about this disorder?
• What are my chances of having other children with Rett syndrome?

What to expect from your doctor

Your health care provider may ask you questions such as:

• When did you first notice your child's unusual behavior or other signs that something may be wrong?
• What could your child do before that your child can no longer do?
• How severe are your child's signs and symptoms? Are they getting progressively worse?
• What, if anything, seems to improve your child's symptoms?
• What, if anything, appears to worsen your child's symptoms?

Your health care provider will ask additional questions based on your responses and your child's symptoms and needs. Preparing and anticipating questions will help you make the most of your appointment time.