Rett Syndrome
Rett syndrome is a rare genetic disorder that disrupts brain development, causing severe physical and mental disabilities primarily in girls. After months of normal growth, children lose abilities they once had—from speaking and walking to using their hands purposefully—creating a profound impact on nearly every aspect of their lives.
Table of contents
- What is Rett Syndrome?
- What Causes Rett Syndrome?
- Signs and Symptoms
- Stages of Rett Syndrome
- Diagnosis
- Treatment and Management
- Living with Rett Syndrome
- Outlook and Life Expectancy
What is Rett Syndrome?
Rett syndrome is a rare and devastating neurodevelopmental disorder (a condition that affects how the brain develops) that impacts nearly every aspect of a person’s life, including their ability to speak, walk, eat, and even breathe[1]. The condition is estimated to affect around 1 in 10,000 girls born each year[5]. It is only rarely seen in boys, who are usually more severely affected[3].
What makes Rett syndrome particularly distressing for families is that babies with the condition typically appear to develop normally for the first six months of life[2]. Parents begin to see their child miss developmental milestones and lose abilities they had already gained, such as the ability to crawl, walk, communicate, or use their hands[1]. Symptoms can begin as early as 6 months old, though the most pronounced changes generally occur between 12 to 18 months of age[2].
Rett syndrome is not a degenerative disorder—meaning it does not continue to worsen indefinitely. Barring illness or complications, individuals with Rett can live into adulthood and beyond, but they require lifelong care[1].
What Causes Rett Syndrome?
Rett syndrome is a genetic disorder caused by changes (mutations) in the MECP2 gene, which is located on the X chromosome[4]. This gene contains instructions for producing a protein called methyl cytosine binding protein 2 (MeCP2), which is needed for brain development and acts as one of the biochemical switches that activate and deactivate other genes[3].
Almost all cases of Rett syndrome are caused by a mutation in the MECP2 gene, which is found on the X chromosome. The MECP2 gene contains instructions for producing a protein that is needed for brain development. When this gene doesn’t function properly in individuals with Rett syndrome, they may have too little of this protein, or the protein they do have doesn’t work properly[3].
There’s usually no family history of Rett syndrome, which means it’s not typically passed from one generation to the next. Almost all cases (over 99%) are spontaneous, with the mutation occurring randomly[5]. Less than 1% of recorded cases are passed from one generation to another[3].
Not everyone who has an MECP2 mutation has Rett syndrome. Scientists believe some cases may be caused by partial gene deletions, mutations in other parts of the MECP2 gene, or additional genes that have not yet been identified[3]. Genetic and environmental factors can contribute to differences in the severity and types of symptoms found in individuals with Rett syndrome[3].
Signs and Symptoms
Children with Rett syndrome have a wide variety of symptoms, and the severity can vary greatly from child to child. Some children with Rett syndrome are affected more severely than others, and the age at which symptoms first appear varies from child to child[5].
The main signs and symptoms include a slowing of development and growth. Brain growth slows after birth, and a smaller than usual head size (called microcephaly) is sometimes the first sign that a child has Rett syndrome[2].
The loss of movement and coordination abilities is often among the first signs. This includes the loss of the ability to use the hands purposefully. Repetitive hand movements are often difficult to control and include wringing, washing, clapping, tapping, squeezing, or repeatedly moving the hands toward the mouth[4]. These characteristic hand movements replace purposeful hand use[2].
Communication and language are severely affected. Children lose the ability to speak or never develop spoken language[2]. There may also be periods of distress, irritability, and sometimes screaming for no obvious reason, as well as social withdrawal—a loss of interest in people and avoidance of eye contact[5].
Walking problems develop, including unsteadiness and awkwardness when walking, difficulty walking, or in some cases, not being able to walk at all[5]. Some children may walk on their toes or have a wide-based gait[3].
Breathing difficulties while awake are common and may include breath holding, hyperventilation (rapid breathing), and swallowing air, which can lead to abdominal bloating[5].
Other symptoms include seizures, sleep problems, difficulty eating, chewing, or swallowing (which can lead to constipation or trouble maintaining a healthy weight), problems with heart rate or heart rhythm, teeth grinding, and scoliosis (curvature of the spine)[4][5].
Life-threatening symptoms may include breathing issues, heartbeat irregularities, and seizures[6].
Stages of Rett Syndrome
Rett syndrome is described in four stages, although symptoms will often overlap between each stage, and not all children go through every stage[5][6].
Stage 1: Early Onset (6 to 18 months)
This stage is sometimes described as “stagnation.” The child’s development slows, and there may be subtle signs that are often overlooked because the changes occur gradually[5]. Symptoms include low muscle tone (hypotonia), difficulty feeding, unusual repetitive hand movements or jerky limb movements, delays in speech development, mobility problems such as problems sitting, crawling and walking, and lack of interest in toys[5]. These symptoms typically begin from 6 to 18 months and often last for several months, although they can persist for a year or more[5].
Stage 2: Rapid Progressive Stage (1 to 4 years)
During this stage, known as “regression” or the “rapid destructive stage,” the child starts to lose some of their abilities[5]. This stage usually begins between the ages of 1 and 4 and may last for any time from 2 months to more than 2 years[5]. The child will gradually or suddenly start to develop severe problems with communication and language, memory, mobility, coordination, and other brain functions. Some of the characteristics and behaviors are similar to those of autism[5]. The child may lose some language skills and the use of their hands, and they may constantly wring their hands[6].
Stage 3: Plateau or Pseudo-Stationary Stage (2 to 10 years)
Stage 3 can begin as early as 2 years or as late as 10 years and often lasts for many years, with many children remaining in this stage for most of their lives[5]. During this stage, some of the stage 2 symptoms may improve—for example, there may be improvements in behavior, with less irritability and crying. The child may become more interested in people and their surroundings, and there may be improvements in alertness, attention span, and communication[5]. Walking may also improve, or the child may learn to walk if they could not before[5]. However, seizures may develop, and irregular breathing patterns may worsen[5].
Stage 4: Deterioration in Movement (years to decades)
Stage 4 can last for years or even decades. The main symptoms at this stage are the development of scoliosis (the spine bending to the left or right side), muscle weakness and spasticity (abnormal stiffness, particularly in the legs), and potentially losing the ability to walk[5]. Communication, language skills, and brain function do not tend to get any worse during stage 4. The repetitive hand movements may decrease, and eye gaze usually improves[5].
Diagnosis
Diagnosing Rett syndrome involves careful observation of a child’s growth and development and answering questions about medical and family history[10]. The diagnosis is usually considered when slowing of head growth is noticed or loss of skills or developmental milestones occurs[10].
For a diagnosis of Rett syndrome, other conditions with similar symptoms must be ruled out. Because Rett syndrome is rare, your child may have certain tests to determine whether other conditions are causing some of the same symptoms[10]. Some of these conditions include other genetic disorders, autism spectrum disorder, cerebral palsy, hearing or vision problems, metabolic disorders, degenerative disorders, brain disorders caused by trauma or infection, and brain damage before birth[10].
Tests may include blood tests, urine tests, imaging tests such as magnetic resonance imaging (MRI) or computerized tomography (CT) scans, hearing tests, eye and vision exams, and brain activity tests called electroencephalograms (EEGs)[10].
Diagnosis of classic Rett syndrome includes these core symptoms, which may start to show up anytime from 6 to 18 months of age: partial or complete loss of purposeful hand skills, partial or complete loss of spoken language, walking problems such as difficulty walking or not being able to walk, and repetitive purposeless hand movements such as hand-wringing, squeezing, clapping or tapping, putting hands in the mouth, or washing and rubbing movements[10].
A genetic DNA blood test can support the diagnosis of Rett syndrome by detecting a change within the MECP2 gene[4]. Most people with a clinical diagnosis of Rett syndrome (80 to 97 percent) have a change in this gene[4]. However, even if an MECP2 variation is found, the child may not be diagnosed with Rett syndrome if they don’t meet the clinical criteria[4].
Treatment and Management
There is no cure for Rett syndrome[5]. Current treatment focuses on improving movement and communication, treating seizures, and providing care and support for children and adults with Rett syndrome and their families[2].
Treatment is directed at managing symptoms and requires a multidisciplinary approach[7]. Any treatment decision should be made based on the individual and family’s needs, goals, and values in consultation with a healthcare provider[11].
The first-ever FDA-approved treatment for Rett syndrome is a medication called trofinetide (sold under the brand name DAYBUE)[13]. This medication was approved in 2023 and is available for the treatment of Rett syndrome in adults and children who are 2 years of age and older[9]. Trofinetide works by reducing inflammation in the brain, stopping certain types of cells from becoming overactive, and increasing the amount of naturally occurring protein called IGF-1[13]. The medication is a liquid given twice a day and is a modifying therapy, similar to treatments for diabetes or multiple sclerosis[13]. Clinical trials showed that parents or caregivers perceived a notable improvement in their child’s presence and engagement[13].
Other medications may be used to control seizures and hand behavior problems, help relieve breathing problems, or help problems with movement[9]. Doctors may give antiseizure medications and behavioral medications to manage specific symptoms[9].
Children with Rett syndrome benefit from various types of health care services. Occupational therapy can improve hand function, reduce repetitive hand movements, and work on daily living skills such as eating and getting dressed[4]. Physical therapy and hydrotherapy can improve mobility and balance[4]. Speech-language therapy helps children learn nonverbal ways to communicate and develop skills to improve social interaction[4]. Nutrition counseling can help children achieve an adequate weight and strengthen their bones[4].
Regular medical re-evaluations are needed to monitor the progression of scoliosis and to monitor heart problems[9]. Nutrition support may be needed to help affected children maintain their weight[9].
Most children with Rett syndrome need extensive social and support services and specialized educational programs[9]. In the United States, the federal Individuals with Disabilities Education Act (IDEA) requires public schools to provide free and appropriate education to children and adolescents with Rett syndrome in the least restrictive, most inclusive setting possible[9].
Living with Rett Syndrome
Living with Rett syndrome is a unique journey, and every stage brings new experiences and challenges. Despite the challenges of Rett, it is possible to have a rich and rewarding life[17].
Building a comprehensive care team is essential. Complete care will likely require doctors from different specialties, including developmental-behavioral pediatrics, pediatric neurology, medical genetics, pediatric cardiology, and pediatric gastroenterology[20].
Managing a chronic health condition takes effort, patience, and time. A little bit of organization can make it easier. Parents and caregivers can help ensure patients receive the best care by keeping meticulous records of health documents and ensuring patients receive regular wellness checks, immunizations, and annual ECGs to monitor heart function[15].
Simple adjustments in the house, such as grab bars, safety rails, and bathing chairs, can help to improve a patient’s quality of life[19]. Orthotics may help with mobility issues, and augmentative and alternative communication methods and aids can help patients better communicate[19].
The importance of physical therapy to individuals with Rett syndrome at all ages cannot be overstated[17]. Physical activity can help to improve cognitive function and work toward greater independence[19]. Building muscle strength through exercise can help maintain existing motor skills and slow deterioration, though exercise should always be performed in consultation with physiotherapists[19].
Sleep issues are common in children with Rett syndrome, observed in about 80% of patients, though the prevalence of sleep problems usually decreases with age[19].
Adequate amounts of calcium, vitamin D, fibers, and fluids must be included in the diet to support bone health and regulate bowel movements[19].
Outlook and Life Expectancy
The severity of the condition is variable, and many of those with the condition live into middle age[2][8]. The average lifespan for patients with Rett syndrome is currently 50 years old[15]. Limited information is available regarding life expectancy due to the rarity of the condition. Almost all Rett patients reach at least age 10, and there are reports of some living well into their 40s and 50s[19].
Early diagnosis and treatment can help with both the length of a patient’s life and its quality[19]. Symptoms that affect a child’s development will stop getting worse (progressing) with time, but they won’t go away. Children will need care and support throughout their life[6].
