Rett syndrome

Overview

Rett syndrome is a rare neurological disorder caused by a genetic mutation that disrupts cellular processes throughout the body, with significant effects on brain development. This alteration of the MECP2 gene, which is located on the X chromosome, is typically spontaneous, meaning it occurs randomly rather than through inheritance.

In the United States, Rett syndrome affects about 1 in 10,000 infants, mostly girls. These babies usually develop normally during the first six to 18 months of life, then plateau and regress, losing acquired skills, such as the ability to crawl, walk or communicate. Some children have more severe impairments – or regress more quickly – than others.

The developmental regression begins at different times for different patients and may last a few months or up to several years. Rett syndrome doesn't progress throughout the lifespan. (People with this condition can live to be middle-aged or older.) Once patients have passed through the regression phase, they can begin to regain skills, such as motor and language abilities, and learn new ones. Most children with Rett syndrome won't fully regain fine motor skills or fluid communication abilities and may need to use a device to help them interact with others.

Recognized as a center of excellence by the International Rett Syndrome Foundation, the UCSF Rett Syndrome Clinic is one of just a few centers in the nation to offer comprehensive care for the condition. Our team of experts ensures that patients can access all necessary services, including physical therapy, orthopedic care, neurology, nutritional counseling and more.

Signs & symptoms

Symptoms of Rett syndrome usually arise during the first two years of life and may include:

• Unusual or distinctive hand movements. These irregular, repetitive motions can include wringing, squeezing, clapping, tapping or rubbing.
• Movement and coordination problems. Children may abruptly lose the ability to walk, crawl, or control their hands.
• Communication problems. Children may lose the ability to talk or communicate verbally. They also may lose nonverbal communication skills, such as making eye contact.
• Breathing abnormalities. Irregular breathing patterns can include hyperventilation, breath-holding or swallowing air.
• Growth abnormalities. Growth and weight gain may slow. Microcephaly (smaller-than-usual head size) and scoliosis (in which the spine curves sideways) may also occur.
• Social, emotional and cognitive impairments. Children may struggle with attention, problem-solving and social interaction. They also may be more irritable or anxious than other kids.
• Seizures. Seizures are common, typically start after age 2, and can vary in type and severity among patients.
• Gastrointestinal problems. People with Rett syndrome may experience constipation, gastroesophageal reflux disease (GERD) or other digestive issues.

Diagnosis

If your child reaches developmental milestones but then plateaus and begins losing skills, such as crawling, walking, talking or using their hands, your pediatrician may suspect Rett syndrome. The next step is a thorough evaluation of your child's and family's medical histories and a physical exam to identify any signs of the disorder.

To confirm a diagnosis of Rett syndrome, your child's provider will order a genetic test to check for a mutation on the MECP2 gene. This requires a small blood sample from your child.

Treatment

Care for Rett syndrome typically involves addressing individual symptoms to improve overall quality of life. While treatments vary based on each patient's needs, they may include medications to alleviate seizures; anxiety; or problems with breathing, sleep or digestion. Physical therapy, speech therapy and nutritional counseling also can help patients achieve the best possible outcomes, including by maximizing their vocabulary and their ability to walk without falling.

In addition, our clinic offers trofinetide (Daybue), the first targeted medical treatment for Rett Syndrome, which was approved by the Food and Drug Administration (FDA) in 2023. This medication, which acts on the brain pathways affected by the MECP2 gene mutation, reduces inflammation in the brain, stopping certain types of cells from becoming overactive and increasing the amount of insulin-like growth factor 1 (IGF-1), a naturally occurring protein involved in growth and development.

Trofinetide is a liquid medication taken by mouth or given through a feeding tube twice a day. During clinical trials (studies to evaluate new therapies), parents and caregivers reported a decrease in symptoms of Rett syndrome. The most common side effects were diarrhea and vomiting.

At UCSF, all patients with Rett syndrome over age 2 are eligible for this treatment. Trofinetide can help in a variety of ways, such as improving verbal skills or walking ability, depending on the patient's symptoms. Because it impacts brain processes related to development, trofinetide may be most helpful if taken early in the course of Rett syndrome, but more research is needed to understand which patients are most likely to benefit. Research is also underway to explore other gene therapies that target the MECP2 gene.