What is Rett syndrome?
Rett syndrome is a neurodevelopmental disorder characterized by typical early growth and development followed by a slowing of development, loss of functional use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.
The course of Rett syndrome, including the age of onset and the severity of symptoms, varies from child to child. Before the symptoms begin, however, the child generally appears to grow and develop, although there are often subtle abnormalities even in early infancy, such as:
- Loss of muscle tone (hypotonia)
- Difficulty feeding
- Jerkiness in limb movements
Gradually, mental and physical symptoms appear. Other early symptoms may include:
- Problems crawling or walking
- Diminished eye contact
The loss of functional use of the hands is followed by compulsive hand movements such as wringing and washing. The onset of this period of regression is sometimes sudden.
Apraxia, which is the inability to perform motor functions, is perhaps the most severely disabling feature of Rett syndrome, interfering with every body movement, including eye gaze and speech.
Children with Rett syndrome often exhibit autistic-like behaviors in the early stages. Other symptoms may include:
Who is more likely to get Rett syndrome?
Rett syndrome is estimated to affect all racial and ethnic groups worldwide. It affects girls almost exclusively. Prenatal testing is available for families with an affected daughter who has an identified MECP2 mutation.
Genetic testing is also available for sisters of girls with Rett syndrome who have an identified MECP2 mutation to determine if they are carriers of the disorder.
The MECP2 gene is found on the X chromosome, one of the two sex chromosomes. Girls have two X chromosomes, but only one is active in any given cell. This means that in a girl with Rett syndrome only a portion of the cells in the nervous system will use the defective
Nearly all cases of Rett syndrome are caused by a mutation in the methyl CpG binding protein 2, or MECP2 (pronounced meck-pea-two) gene. The MECP2 gene contains instructions for the synthesis of a protein called methyl cytosine binding protein 2 (MeCP2), which is needed for brain development and acts as one of the many biochemical switches that can either increase gene expression or tell other genes when to turn off and stop producing their own unique proteins. Because theMECP2 gene does not function properly in individuals with Rett syndrome, insufficient amounts or structurally abnormal forms of the protein are produced and can cause other genes to be abnormally expressed.
Not everyone who has an MECP2 mutation has Rett syndrome. Scientists have identified mutations in the CDKL5 and FOXG1 genes in individuals who have atypical or congenital Rett syndrome, but they are still learning how those mutations cause the disorder. Scientists believe the remaining cases may be caused by partial gene deletions, mutations in other parts of the MECP2 gene, or additional genes that have not yet been identified, and they continue to look for other causes.
Although Rett syndrome is a genetic disorder, less than one percent of recorded cases are inherited or passed from one generation to the next. Most cases are spontaneous, which means the mutation occurs randomly. However, in some families of individuals affected by Rett syndrome, there are other female family members who have a mutation of their MECP2 gene.
How is Rett syndrome diagnosed and treated?
Diagnosing Rett syndrome
Doctors diagnose Rett syndrome by observing signs and symptoms during the child's early growth and development and conducting ongoing evaluations of the child's physical and neurological status. Scientists have developed a genetic test to complement the clinical diagnosis, which involves searching for the MECP2 mutation on the child's X chromosome. A pediatric neurologist, clinical geneticist, or developmental pediatrician should be consulted to confirm the diagnosis of Rett syndrome.
Treating Rett syndrome
There is no cure for Rett syndrome. Treatment for the disorder is symptomatic—focusing on the management of symptoms—and supportive, requiring a multidisciplinary approach. Medication may be needed for breathing irregularities and motor difficulties, and anticonvulsant drugs may be used to control seizures. There should be regular monitoring for scoliosis and possible heart abnormalities. Occupational therapy can help children develop skills needed for performing self-directed activities (e.g., dressing, feeding, and practicing arts and crafts), while physical therapy and hydrotherapy may prolong mobility.
Some children may require special equipment and aids such as braces to arrest scoliosis, splints to modify hand movements, and nutritional programs to help them maintain adequate weight. Special academic, social, vocational, and support services may be required in some cases.
Despite the difficulties with symptoms, many individuals with Rett syndrome continue to live into middle age and beyond. Because the disorder is rare, very little is known about long-term prognosis and life expectancy.
What are the latest updates on Rett syndrome?
The National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Mental Health (NIMH), and the Office of Rare Diseases Research (ORDR) support research on Rett syndrome.
Understanding the cause is necessary for developing new therapies to manage specific symptoms, as well as for providing better methods of diagnosis. The discovery of the main Rett syndrome gene (MECP2) in 1999 provides a basis for further genetic studies and enables the use of recently developed animal models such as transgenic mice which are deficient in MECP2. These mice have neurologic abnormalities that can be reversed by activating the MECP2 gene later in life.
One NINDS-supported study looks for mutations in the MECP2 gene of individuals with Rett syndrome to learn about MeCP2 protein function and dysfunction. Information from this study will increase understanding of the disorder and may lead to new therapies. Other research aims at identifying molecular pathways that are affected by the dysfunction, developing animal models of the disorder, and early-stage therapy development.
Some researchers suggest that the specific type of mutation in the MECP2 gene affects the severity of symptoms of Rett syndrome. Studies are now underway to understand each mutation that may cause the features of Rett syndrome, and how these mutations might change the features of the syndrome. One NIH-funded study of the natural history of Rett syndrome should also provide new information about these topics.
Scientists know that lack of a properly functioning MeCP2 protein disturbs the function of mature brain cells, but they do not know the exact mechanisms by which this happens. Investigators are trying to find other genetic switches that operate in a similar way to the MeCP2 protein. Once they discover how the protein works and locate similar switches, they may devise therapies that can substitute for the malfunctioning switch. Another outcome might involve manipulating other biochemical pathways to compensate for the malfunctioning MECP2 gene, thereby preventing progression of the disorder. Gene therapy to achieve regulated expression of a normal MECP2 gene is also under study in animal models.
Researchers are also trying to find other genes that may be involved in Rett syndrome. Some studies have helped to narrow the search for these genes, but much is still unknown about how these genes may cause or contribute to Rett syndrome.
How can I or my loved one help improve care for people with Rett syndrome?
Consider participating in a clinical trial so clinicians and scientists can learn more about Rett syndrome and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with Rett syndrome at Clinicaltrials.gov.
Where can I find more information about Rett syndrome?
Information may be available from the following organizations: