Rett syndrome Health Article

Definition

Rett syndrome is a disorder of the nervous system that leads to developmental reversals, especially in the areas of expressive language and hand use.

Causes, incidence, and risk factors

Rett syndrome occurs almost exclusively in girls and may be misdiagnosed as autism or cerebral palsy.

Studies have linked 75% of Rett syndrome cases to a defect in the methl-CpG-binding protein 2 (MeCP2) gene. The gene associated with Rett syndrome is on the X chromosome. Females have two X chromosomes, so even when one has this significant defect, the other X chromosome provides enough normal protein for the child to survive.

Males born with this defect do not have a second X chromosome to compensate for the problem. Therefore, the defect is usually lethal, leading to miscarriage, stillbirth, or very early death.

Most cases of the defect occur without causes. However, there seem to be groups of the disease within families and certain geographic regions, for example Norway, Sweden, and northern Italy.

Symptoms

An infant with Rett syndrome usually has normal development for the first 6 - 18 months. Symptoms range from mild to severe.

Symptoms may include:

• Hypotonia (floppy arms and legs) -- frequently the first sign
• Slowing head growth beginning at approximately 5 - 6 months of age
• Change in development
• Severe language development problems
• Loss of purposeful hand movements; for example, the grasp used to pick up small objects is replaced by repetitive hand motions like hand wringing or constant placement of hands in mouth
• Apraxia
• Shaky, unsteady, or stiff gait; or toe walking
• Loss of social engagement
• Seizures
• Breathing problems -- problems tend to get worse with stress; breathing is usually normal during sleep and abnormal while awake
• Scoliosis
• Loss of normal sleep patterns
• Poor circulation that can lead to cold and bluish arms and legs
• Intellectual disabilities and learning difficulties (assessing cognitive skills in those with Rett syndrome, however, is difficult because of the speech and hand motion abnormalities)
• Gastrointestinal problems including ongoing, severe constipation and gastroesophageal reflux (GERD)
• Excessive saliva and drooling

Signs and tests

Genetic tests may be used to search for the gene mutations that cause Rett syndrome. However, since this gene defect is not identified in everyone with the disease, the diagnosis of Rett syndrome is still based on the symptoms.

There are several different types of Rett syndrome:

• Classical (meets the diagnostic criteria)
• Provisional (some evidence between ages 1 and 3)
• Atypical

Rett syndrome is classified as atypical if:

• It begins early (soon after birth) or late (beyond 18 months of age, sometimes as late as 3 or 4 years old).
• Speech and hand skill problems are mild.
• It is found in a boy (very rare).

Treatment

Treatment may include:

• Assistance with feeding, diapering, and treating symptoms like constipation and GERD).
• Supplemental feeding for those with slowed growth. Diets high in calories and fat, as well as nasogastric tube feeds, can help increase weight and height. Weight gain, in turn, may improve alertness and social interactions. If the person with Rett syndrome is prone to breathing in food, a feeding tube into the stomach may be recommended.
• Physical therapy for the hands to prevent them from contracting. Also, weight bearing exercises and frequent followup are recommended for those with scoliosis.
• Medication, like carbamazepine, to treat seizures.

Other medications or supplements that have been used or studied include:

• L-dopa for motor rigidity in later stages of the disease
• L-carnitine -- some families report improvement in language skills, increased muscle mass, decreased constipation, increased alertness, less daytime sleeping, increased energy, and improved quality of life while their daughters took carnitine
• Folate and betaine
• Dextromethorphan
• Bromocriptine

Given the discovery of a genetic mutation associated with Rett syndrome, research using gene therapy is underway. Stem cell therapy, alone or in combination with gene therapy, is another hopeful treatment that requires thorough study.

Problems in breathing pattern may be the most upsetting and difficult symptom for parents to watch. Why they happen and what to do about them is not well understood. Studies are underway to evaluate various treatments, such as buspirone (Buspar), naltrexone, or magnesium citrate.

Most experts in Rett syndrome recommend that parents remain calm through an episode of irregular breathing like breath holding. It may help to remind yourself that normal breathing always returns and that your daughter will grow accustomed to the abnormal breathing pattern.

Support Groups

International Rett Syndrome Association - www.rettsyndrome.org