Rett syndrome is a brain disorder that occurs almost exclusively in girls and it is a rare genetic neurological and developmental disorder that affects the way the brain develops, causing a progressive inability to use muscles for eye and body movements and speech. . The most common form of the condition is known as classic Rett syndrome. After birth, girls with classic Rett syndrome have 6 to 18 months of apparently normal development before developing severe problems with language and communication, learning, coordination, and other brain functions. Early in childhood, affected girls lose purposeful use of their hands and begin making repeated hand wringing, washing, or clapping motions. They tend to grow more slowly than other children and have a small head size (microcephaly). Other signs and symptoms that can develop include breathing abnormalities, seizures, an abnormal side-to-side curvature of the spine (scoliosis), and sleep disturbances.
Researchers have described several variant or atypical forms of Rett syndrome, which can be milder or more severe than the classic form. Although there's no cure for Rett syndrome, potential treatments are being studied. Current treatment focuses on improving movement and communication and providing care and support for children and adults with Rett syndrome and their families.
Babies with Rett syndrome are generally born after a normal pregnancy and delivery. The age at which symptoms begin and their severity and associated disability varies widely among individuals. However, most babies with Rett syndrome seem to grow and behave normally 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, suddenly, or over a period of weeks or months.
Rett syndrome signs and symptoms include:
- Slowed growth. Brain growth slows after birth. Smaller than normal head size (microcephaly) is usually the first sign that a child has Rett syndrome. As children get older, delayed growth in other parts of the body becomes evident.
- Loss of normal movement and coordination. The first signs often include reduced hand control and a decreasing ability to crawl or walk normally. At first, this loss of abilities occurs rapidly and then it continues more gradually. Eventually muscles become weak or may become rigid or spastic with abnormal 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 speech. Over time, most children gradually regain eye contact and develop nonverbal communication skills.
- Abnormal hand movements. Children with Rett syndrome typically develop repetitive, purposeless hand movements that may differ for each person. Hand movements may include hand wringing, squeezing, clapping, tapping or rubbing.
- 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, abnormally rapid breathing (hyperventilation), forceful exhalation of air or saliva, and swallowing air. These problems tend to occur during waking hours, but not during sleep.
- Agitation and irritability. Children with Rett syndrome 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.
- Other abnormal behaviors. These may include, for example, sudden, odd facial expressions and long bouts of laughter, hand licking, and grasping of hair or clothing.
- Cognitive disabilities. Loss of skills can be accompanied by a loss of intellectual functioning.
- Seizures. Most people who have Rett syndrome experience seizures at some time during their lives.
- Abnormal curvature of the spine (scoliosis). Scoliosis is common with Rett syndrome. It typically begins between 8 and 11 years of age and increases 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.
- Pain. Because of health problems, people with Rett syndrome may have an increased risk of pain. But communication problems may prevent others from recognizing these pain issues. In one small study, one-fourth of the parents estimated that their daughters have more than a week of pain each month.
- Other symptoms. A variety of other symptoms can occur, such as thin, fragile bones prone to factures; small hands and feet that are usually cold; problems with chewing and swallowing; and teeth grinding. Symptoms can vary greatly from child to child.
Stages of Rett syndrome:
Rett syndrome is commonly divided into four stages:
- Stage I: early onset. Signs and symptoms are subtle and easily overlooked during the first stage, which starts between 6 and 18 months of age and 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 II: rapid destruction. 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 III: plateau. The third stage usually begins between the ages of 2 and 10 years and can last for many years. Although problems with movement continue, behavior may have limited improvement, with less crying and irritability, and some improvement in hand use and communication. Seizures may begin in this stage and generally don't occur before the age of 2.
- Stage IV: 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.
When to see a doctor:
Signs and symptoms of Rett syndrome can be subtle in the early stages. See your child's doctor right away if you begin to notice physical problems or changes in behavior after apparently normal development, such as:
- 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 normal play
- Delayed speech development or loss of previously acquired speech abilities
- Problem behavior or marked mood swings
- Any clear loss of previously gained milestones in gross motor or fine motor skills
Rett syndrome is a rare genetic disorder. Classic Rett syndrome, as well as five known variations (atypical or variant) with milder or more severe symptoms, can occur based on the specific genetic mutation.
Rett syndrome is typically caused by changes (mutations) in the MECP2 gene and is usually inherited in an X-linked dominant manner. The vast majority of cases are not inherited from a parent, but are due to a new mutation in the affected person. This gene provides instructions for making a protein (MeCP2) needed for the development of the nervous system and normal brain function. Mutations in the MECP2 gene that cause Rett syndrome can change the MeCP2 protein or result in the production of too little protein, which appears to disrupt the normal function of neurons and other cells in the brain. Only in a few cases is this genetic disorder inherited. The mutation appears 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.
Several conditions caused by changes in other genes (such as FOXG1 syndrome) have overlapping signs and/or symptoms of Rett syndrome. These conditions were once thought to be variant forms of Rett syndrome, but are now usually considered to be separate disorders.
Rett syndrome in boys:
Because males have a different chromosome combination from females, boys who have the genetic mutation that causes Rett syndrome are affected in devastating ways. Most of them die before birth or in early infancy.
A very small number of boys have a different mutation that results in a less destructive form of Rett syndrome. Similar to girls with Rett syndrome, these boys will likely live to adulthood, but they're still at risk of a number of intellectual and developmental problems.
There's no known way to prevent Rett syndrome. In most cases, the genetic mutation that causes the disorder occurs spontaneously. Even so, if you have a child or other family member with Rett syndrome, you may want to ask the doctor about genetic testing.
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.
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 identify if other conditions are causing some of the same symptoms as Rett syndrome. Some of these conditions include:
- Other genetic disorders
- 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)
Criteria for diagnosis:
A diagnosis of classic Rett syndrome includes these core symptoms:
- Partial or complete loss of purposeful hand skills
- Partial or complete loss of spoken language
- Walking abnormalities, such as problems 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 typical symptoms can support the diagnosis.
Diagnostic criteria for atypical or variant Rett syndromes may vary slightly, but the symptoms are the same, with varying degrees of severity.
If your child's doctor suspects Rett syndrome after evaluation, he or she may recommend a genetic test (DNA analysis) to confirm the diagnosis. The test requires drawing a small amount of blood from a vein in the arm. The blood is then sent to a lab, where technicians examine your child's DNA for abnormalities and clues as to the cause and severity of the disorder.
Males with pathogenic MECP2 mutations usually die within the first 2 years from severe encephalopathy, unless they have an extra X chromosome (often described as Klinefelter syndrome), or have somatic mosaicism.
Male fetuses with the disorder rarely survive to term. Because the disease-causing gene is located on the X chromosome, a female born with a MECP2 mutation on her X chromosome has another X chromosome with an ostensibly normal copy of the same gene, while a male with the mutation on his X chromosome has no other X chromosome, only a Y chromosome; thus, he has no normal gene. Without a normal gene to provide normal proteins in addition to the abnormal proteins caused by a MECP2 mutation, the XY karyotype male fetus is unable to slow the development of the disease, hence the failure of many male fetuses with a MECP2 mutation to survive to term. Females with a MECP2 mutation, however, have a non-mutant chromosome that provides them enough normal protein to survive longer. Research shows that males with Rett syndrome may result from Klinefelter's syndrome in which, the male has an XXY karyotype. Thus, a non-mutant MECP2 gene is necessary for a Rett's-affected embryo to survive in most cases, and the embryo, male or female, must have another X chromosome.
There have, however, been several cases of 46,XY karyotype males with a MECP2 mutation (associated with classical Rett syndrome in females) carried to term, who were affected by neonatal encephalopathy and died before 2 years of age. The incidence of Rett syndrome in males is unknown, partly owing to the low survival of male fetuses with the Rett syndrome-associated MECP2 mutations, and partly to differences between signs caused by MECP2 mutations and those caused by Rett's.
Females can live up to 40 years or more. Laboratory studies on Rett syndrome may show abnormalities such as:
- EEG abnormalities from 2 years of age
- atypical brain glycolipids
- elevated CSF levels of beta-endorphins and glutamate
- reduction of substance P
- decreased levels of CSF nerve growth factors
A high proportion of deaths are abrupt, but most have no identifiable cause; in some instances death is the result most likely of:
- spontaneous brainstem dysfunction
- cardiac arrest, likely due to long QT syndrome, ventricular tachycardia or other arrhythmias.
- gastric perforation
Although there is no cure for Rett syndrome, treatments are directed toward symptoms and providing support. 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 and GI and heart problems is needed.
- Medications. Though medications can't cure Rett syndrome, they may help control some signs and symptoms associated with the disorder, such as 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 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 normal growth and for improved mental 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.
- Support services. Academic, social and job training services may help with integration into school, work and social activities. Special adaptations may make participation possible.
- Genetics Home Reference
- Mayo Clinic