Rett Syndrome

NewsRx Bundle A quick and inexpensive way to view the most recent articles for a one-time project. Custom Reports on Rett Syndrome Tired of prepackaged reports that just don't meet your needs? Target your needs!

What is Rett syndrome?

Rett syndrome is a disorder of brain development that occurs almost exclusively in girls. After 6 to 18 months of apparently normal development, girls with the classic form of Rett syndrome develop 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 can include breathing abnormalities, seizures, an abnormal curvature of the spine (scoliosis), and sleep disturbances.

Researchers have described several variants of Rett syndrome with overlapping signs and symptoms. The atypical forms of this disorder range from a mild type, in which speech is preserved, to a very severe type that has no period of normal development. A form of Rett syndrome called the early-onset seizure variant has most of the characteristic features of classic Rett syndrome, but also causes seizures that begin in infancy.

How common is Rett syndrome?

This condition affects an estimated 1 in 10,000-22,000 females.

What genes are related to Rett syndrome?

Mutations in the CDKL5 and MECP2 genes cause Rett syndrome.

Most cases of classic Rett syndrome are caused by mutations in the MECP2 gene. This gene provides instructions for making a protein (MeCP2) that is critical for normal brain development. The MeCP2 protein likely plays a role in forming connections (synapses) between nerve cells. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them off when they are not needed. The MeCP2 protein may also control the production of different versions of certain proteins in nerve cells. Although mutations in the MECP2 gene disrupt the normal function of nerve cells, it is unclear how these mutations lead to the signs and symptoms of Rett syndrome.

Males with mutations in the MECP2 gene often die before birth or in infancy. A small number of males with a MECP2 mutation, however, have developed signs and symptoms similar to those of classic Rett syndrome. Some of these boys have an extra X chromosome in many or all of the body's cells. The extra X chromosome contains a normal copy of the MECP2 gene, which produces enough of the MeCP2 protein for the boys to survive. Other males with features of Rett syndrome have mutations in the MECP2 gene that occur after conception and are present in only a fraction of the body's cells. In rare cases, researchers have discovered that the MECP2 gene is abnormally duplicated in boys with mental retardation and some developmental problems characteristic of Rett syndrome.

Mutations in the CDKL5 gene cause an atypical form of Rett syndrome in females called the early-onset seizure variant. The CDKL5 gene provides instructions for making a protein that appears to be essential for normal brain development. Although the function of this protein is unknown, it may play a role in regulating the activity of other genes. Researchers are working to determine how mutations in the CDKL5 gene lead to seizures and the features of Rett syndrome in affected girls.

How do people inherit Rett syndrome?

More than 99 percent of classic Rett syndrome cases occur in people with no history of the disorder in their family. Many of these cases result from new mutations in the MECP2 gene.

A few families have been described with more than one affected family member. These cases helped researchers determine that Rett syndrome has an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.

Source: National Institutes of Health

Study results from Center for Molecular and Human Genetics in the area of autism in children published

"For most, referrals occurred after evaluation by a developmental pediatrician and/or psychologist to establish the diagnosis. Tiered laboratory testing for the majority of the patients followed a guideline that was developed in collaboration with clinicians at The Autism Center at Children's Hospital, Columbus, OH. The patients included 57 males and 14 females; 57 met DSM-IV criteria for autism, with the rest being Asperger or pervasive developmental disorder not otherwise specified. Macrocephaly [head circumference (HC) >or=95%] was present in 19 (27%). Two children had visible chromosome abnormalities (47,XYY; 48,XY + 2mar/49,XY + 3mar). Two patients with autism and macrocephaly had heterozygous mutations in the PTEN tumor suppressor gene. Three females had Rett syndrome, each confirmed by DNA sequencing of the MECP2 gene. Extensive metabolic testing produced no positive results, nor did fragile X DNA testing. The overall diagnostic yield was 10% (7/71). PTEN gene sequencing should be considered in any child with macrocephaly and autism or developmental delay," wrote G.E. Herman and colleagues, Center for Molecular and Human Genetics.

The researchers concluded: "Metabolic screening may not be warranted in autism spectrum disorders without more specific indications or additional findings."

Herman and colleagues published their study in Genetics In Medicine (Genetic testing in autism: how much is enough? Genetics In Medicine, 2007;9(5):268-74).

For additional information, contact G.E. Herman, Center for Molecular and Human Genetics, Columbus Children's Research Institute, Columbus, Ohio 43205 USA.

Publisher contact information for the journal Genetics In Medicine is: Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

Keywords: United States, Columbus, Autism, Developmental Disabilities, Genetics, Neurology.

This article was prepared by Mental Health Weekly Digest editors from staff and other reports. Copyright 2007, Mental Health Weekly Digest via NewsRx.com.