Rett syndrome is a progressive neurological disorder seen almost exclusively in females. The most common symptoms include decreased speech, mental retardation, severe lack of coordination, small head size, and unusual hand movements.
Description
Dr. Andreas Rett first reported females with the symptoms of Rett syndrome in 1966. Females with this X-linked dominant genetic condition are healthy and of average size at birth. During infancy, head growth is abnormally slow and microcephaly (small head size) develops. Babies with Rett syndrome initially have normal development. At approximately one year of age, development slows and eventually stops. Patients with Rett syndrome develop autistic features. Involuntary hand movements are a classic feature of Rett syndrome.
Females with Rett syndrome may also develop seizures, curvature of the spine (scoliosis), irregular breathing patterns, swallowing problems, constipation, and difficulties walking. Some females with Rett syndrome are unable to walk. There is currently no cure for Rett syndrome. Most girls with Rett syndrome live until adulthood. The gene responsible for Rett syndrome has been identified and genetic testing is available.
Genetic profile
Rett syndrome is an X-linked condition. This means that the mutation (genetic change) responsible for Rett syndrome affects a gene located on the X chromosome. The affected gene is the methyl CpG-binding protein 2 (MECP2) gene. This gene makes a protein that regulates other genes. When there is a mutation in MECP2, the protein it makes does not work properly. This is thought to prevent normal neuron (nerve cell) development.
Rett syndrome is considered to be X-linked dominant in nature. Males have one X chromosome and one Y chromosome. Females have two X chromosomes. Males with a mutation in their MECP2 gene typically die as infants or are miscarried before birth. Rett syndrome is usually considered fatal in males because the Y chromosome cannot compensate for the MECP2 mutation on the X chromosome. Females with a mutation in the MECP2 gene develop Rett syndrome, but the presence of the second X chromosome in females carrying a normal MECP2 gene enables them to survive.
The severity of the syndrome in females is related to the type of mutation in the MECP2 gene and the activity of the X chromosomes. Normally, both X chromosomes have the same activity. However, the activity can be unequal. If the X chromosome with the mutation in the MECP2 gene is more active than the X chromosome without the mutation, the female is more severely
affected. The reverse is also true. If the X chromosome without the mutation is more active than the X chromosome with the mutation, the female is less severely affected.
If a woman has a mutation in her MECP2 gene, she has a 50% risk with any pregnancy to pass on her X chromosome with the mutation. However, it is uncommon for women with Rett syndrome to have children due to the severity of the disorder.
Demographics
The incidence of Rett syndrome is thought to be between 1 in 10,000 and 1 in 20,000 live births. It is seen almost exclusively in females. The vast majority of cases of Rett syndrome are sporadic in nature. Therefore, the risk of a family having more than one affected daughter is typically very low.
Signs and symptoms
Infants with Rett syndrome typically have normal size at birth. They develop normally until approximately 6–18 months of age. Development then slows, eventually stops, and soon regresses. Affected individuals are unable to do things they were once able to do. Girls with Rett syndrome lose the ability to speak, become uninterested in interacting with others, and stop voluntarily using their hands. The loss of language and eye contact causes girls with Rett syndrome to appear to be autistic. Between one and three years of age, girls with Rett syndrome develop the unusual hand movements that are associated with the disease. Patients wring their hands, clap their hands, and put their hands in their mouth involuntarily. Some patients with Rett syndrome also lose the ability to walk. If the ability to walk is maintained, the gait is very ataxic (uncoordinated, clumsy).
By preschool age the developmental deterioration of girls with Rett syndrome stops, but they continue to have lack of speech, inability to understand language, poor eye contact, mental retardation, ataxia, and apraxia (inability to make purposeful movements). Other common symptoms associated with Rett syndrome include seizures, constipation, irregular breathing, scoliosis, swallowing problems, teeth grinding, sleep disturbances, and poor circulation. As patients with Rett syndrome get older, their ability to move decreases and spasticity (rigidity of muscles) increases.
Diagnosis
The diagnosis of Rett syndrome is made when the majority of the symptoms associated with the disease are present. If a physician suspects an individual has Rett syndrome, DNA testing is recommended. Approximately 75% of patients with Rett syndrome have a mutation in the MECP2 gene. DNA testing can be performed on a blood sample, or other types of tissue from the body. If a mutation is found in the MECP2 gene, the diagnosis of Rett syndrome is confirmed.
Treatment and management
As of 2001, there is not a cure for Rett syndrome. Treatment of patients with Rett syndrome focuses on the symptoms present. Treatment may include medications that inhibit seizures, reduce spasticity, and prevent sleep disturbances. Nutrition is monitored in females with Rett syndrome due to their small stature and the constipation associated with the disorder.
Prognosis
In the absence of severe medical problems, most patients with Rett syndrome live into adulthood.
BOOKS
Zoghbi, Huda, and Uta Francke. "Rett Syndrome." In The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill, 2001.
PERIODICALS
Percy, Alan. "Genetics of Rett Syndrome: Properties of the Newly Discovered Gene and Pathophysiology of the Disorder." Current Opinion in Pediatrics 12 (2000): 589-595.
ORGANIZATIONS
Alliance of Genetic Support Groups. 4301 Connecticut Ave. NW, Suite 404, Washington, DC 20008. (202) 966-5557. Fax: (202) 966-8553. <http://www.geneticalliance.org>.
International Rett Syndrome Association. 9121 Piscataway Rd., Clinton, MD 20735. (800) 818-RETT. <http://www.rettsyndrome.org>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
Rett Syndrome Research Foundation. 4600 Devitt Dr., Cincinnati, OH 45246. <http://www.rsfr.org>.
