Rett Syndrome is a severe, progressive neurological disorder that causes developmental regression, especially in the areas of expressive language and hand use. It occurs almost exclusively in girls.

The gene associated with this disorder was recently identified on the X-chromosome. This gene contains instructions for creating methl-CpG-binding protein 2 (MeCP2), a protein that regulates the manufacture of various other proteins.

Mutations in the gene leads to the production of incorrect proteins, which causes damage in the maturing brain. The severity of the disease is linked to specific types of mutation.

Females have two X chromosomes, so even when one has this significant mutation, the other X chromosome provides enough normal protein for the child to survive.

Males conceived with this mutation are usually miscarried (spontaneously aborted) during pregnancy because they do not have a second X chromosome to compensate for the problem.

Most cases (99.5%) are due to spontaneous mutations, rather than inheritance. However, the occurrence within families is higher than would be expected by chance, so there may be an inherited factor involved.

An infant with Rett syndrome develops normally for the first few months. Then symptoms may occur:

• Hypotonia, or floppy extremities (frequently the first sign)
• Slowing head growth beginning at approximately 5-6 months of age
• Developmental regression
• Severely impaired language development, both expressed and understood
• Loss of meaningful hand use, replaced by hand wringing or placement of hand in mouth
• Autistic-like behavior, loss of social engagement
• Seizures (1/3 of patients)
• Intermittent hyperventilation with a disorganized breathing pattern

Chromosomal analysis may now be used to search for the gene mutation that causes Rett syndrome. Recent studies have now shown that mutations of the MeCP2 gene can be found in 75% of girls with Rett syndrome.

• Supportive care (assistance with feeding, diapering)
• Physical therapy for the hands to prevent them from contracting
• Carbamazepine to treat seizures (also may improve alertness)

Various other treatments have been tried, including carnitine and ketogenic diets, but without promising results.

For additional information and resources, see the International Rett Syndrome Association.

Progression of this disease usually levels off once the patient reaches adolescence. The seizures may subside and hand use may improve. However, all individuals with Rett syndrome still have profound mental retardation.

Discovery of the gene that causes Rett syndrome will help in understanding the disease.