Rett syndrome is a neurodevelopmental disorder, meaning it affects the development of the brain and nervous system, as well as some other features of growth, such as height.
This condition mostly affects females. Although it’s a genetic condition, Rett syndrome is rarely passed through families.
Rett syndrome is not life threatening, but it can severely limit the function of anyone with the condition. There is no known cure.
This article will cover the causes of Rett syndrome, what symptoms to expect if someone you know has this condition, and the treatment options.
Sex is determined by chromosomes, and gender is a social construct that can vary between time periods and cultures. Both of these aspects are acknowledged to exist on a spectrum both historically and by modern scientific consensus.
We use “male” and “female” to refer to someone’s sex as determined by their chromosomes, and “boy” and “girl” when referring to their gender (unless quoting from sources using nonspecific language).
Rett syndrome is a congenital disorder, but it is not usually apparent until 6 to 18 months of age.
Named after Dr. Andreas Rett, an Austrian physician who first described the condition in 1966, Rett syndrome was not widely recognized until a second study identified more people with this syndrome in 1983.
How Rett syndrome appears varies in symptoms and severity from person to person. Subtle symptoms might be present before a diagnosis is made because of typical differences in growth and development rates.
However, as children — mostly females — affected by this condition move through their first year of life, the mental and physical signs of Rett syndrome become more obvious.
Rare in males
Rett syndrome is rare, occurring only in about 1 in 10,000 female births. The condition is even rarer in males, mainly because males affected by this mutation do not survive pregnancy.
Since Rett syndrome is a condition that develops from a mutation in the X chromosome — of which males only have one —pregnancies with males affected by this condition usually end in miscarriage or stillbirth.
In the beginning, infants born with Rett syndrome appear to develop typically. Over time, symptoms may appear, such as:
- muscle weakness
- keeping to themselves
- lack of eye contact or interaction with others
- inability to focus
As children with this condition get older, the physical and neurological symptoms become worse. Those with Rett syndrome may lose the ability to walk, talk, or control their movements.
About 85 to 90 percent of people with this condition have growth delays and muscle wasting. These symptoms get worse with age. Children with this condition who live into adulthood often require constant care.
X chromosome inactivation
Some females with Rett syndrome have evidence of chromosome inactivation on genetic testing. The mutation that causes Rett syndrome always affects just one of two X chromosomes in an infant.
Sometimes, the affected chromosome may be silenced or essentially turned off, which can mask or lessen symptoms of this disorder.
Since males carry just one X and one Y chromosome, this phenomenon only occurs in females.
Rett syndrome is a genetic disorder caused by a mutation of the X chromosome in the MECP2 gene. More than 900 mutations of this gene are possible. The symptoms and severity of Rett syndrome depend on the exact location and type of mutation.
Mutations that lead to Rett syndrome are usually located in one of eight different areas of the MECP2 gene known as “hot spots.” This gene usually creates a protein that helps control brain function and activity.
The exact role of this protein is not clear, but lower levels of this protein are often found in people with Rett syndrome.
Although this condition is caused by a genetic mutation, it’s not usually hereditary. About 99 percent of the mutations that lead to Rett syndrome happen spontaneously and are not transferred to a child from their parents.
In less than 1 percent of cases, parents who have a child with Rett syndrome will have another child with the same condition. This can happen if one parent has egg or sperm cells that carry a mutation in the MECP2 gene.
Birthing parents who carry this mutation have a 50 percent chance of passing it on to their children, depending on how many cells in an egg are affected.
The progression of Rett syndrome throughout infancy and childhood is usually divided into four stages.
The first stage is usually missed because symptoms are subtle and may be explained by development delays. But there might be some red flags in early infancy, including:
- loss of muscle tone (hypotonia)
- feeding difficulties
- jerky limb movements
- repetitive hand movements
Stage 1 continues until around the time of diagnosis, which is usually around 6 to 18 months. Symptoms that appear later in stage 1 are more noticeable and may come on suddenly. The progression of stage 1 can take months or even up to a year.
Examples of symptoms that can appear later in stage 1 include:
- difficulty crawling or walking
- diminished eye contact
- lack of interest in parents or activities
- regression of skills or behaviors
- compulsive hand movements, like wringing or washing movements
- walking tip-toed
- autistic-like behaviors
- cognitive difficulties
- teeth grinding
- slow growth
- smaller head size (microcephaly)
Stage 2 is known as the “rapid destructive phase.” This stage usually happens between the ages of 1 and 4 and can last weeks or months. During this time, the following things can happen:
- loss of purposeful hand skills
- speech difficulties or total speech loss
- more noticeable repetitive hand movements that disappear during sleep
- breathing difficulties, like apnea or hyperventilation
- loss of social skills
- unsteady walking
- slow motor movements
- trouble sleeping
- screaming fits or uncontrollable crying
- panic attacks
In stage 3, symptoms may appear to stop progressing. This stage is sometimes called the “plateau or pseudo-stationary stage.” Some children have improved behaviors during this time, like:
- improved communication skills
- less crying and irritability
- increased interest in people and things
- stability of neurological symptoms
This stage can last for years, but despite some improvements, there are still some serious symptoms displayed during this time. These may include:
- difficulty performing purposeful, skilled, or learned movements
- difficulties with motor skills
- slow growth rates
Some children with Rett syndrome can stay in this stage for most of their lives, and it typically begins between the ages of 2 and 10.
Many children with this condition can live well into adulthood, but late motor skill difficulties can appear. Some people with this condition never learn to walk and may experience things like:
- increasing muscle weakness
- joint contractures
- muscle spasms
- underdeveloped hands and feet that are often cold
- uncontrolled movements and muscle contractions
- improper postures
- decreased facial expression (hypomimia)
- difficulty chewing and swallowing
- muscle wasting
- digestive problems
- atypical breathing
- intermittent eye crossing (esotropia)
- bone loss (osteopenia)
- heart irregularities
Rett syndrome is often misdiagnosed, as its symptoms can be similar to other neurodevelopmental disorders. In the past, Rett syndrome was sometimes diagnosed as a different medical condition, especially autism.
Autism and Rett syndrome share symptoms, such as people having communication delays and difficulty with social relationships.
However, there are many physical symptoms of Rett syndrome that do not appear in autistic people. Also, unlike autism, females are almost exclusively affected by Rett syndrome.
The next section will give more details about how Rett syndrome is diagnosed and how doctors can differentiate it from other similar conditions.
Rett syndrome is diagnosed through the observation of clinical symptoms and growth patterns of affected children.
There is also a genetic test that can detect the mutation of the MECP2 gene, but a pediatric neurologist, clinical geneticist, or development pediatrician should confirm the results.
There are three types of diagnostic criteria that can be used to confirm Rett syndrome.
Main diagnostic criteria
These include the presence of symptoms like:
- loss of acquired hand skills
- loss of spoken language
- repetitive hand movements
- difficulty walking
- walking tip-toed or stiff-legged
Supportive diagnostic criteria
These symptoms do not develop in everyone, but they may appear at a later age in some females. However, they’re not required for a diagnosis. Supportive diagnostic symptoms can include things like:
- teeth grinding
- cold hands and feet
- small hands and feet in relation to height
- low weight
- reduced height
- atypical sleep patterns
- decreased muscle tone
- inappropriate laughing or screaming
- intense eye gaze
- decreased pain responses
The presence of these symptoms alone is not enough for a diagnosis of Rett syndrome. Symptoms from the other categories must be present as well.
These are things a doctor will look for that rule out a Rett syndrome diagnosis. Children with the following conditions allow a doctor to rule out Rett syndrome:
- brain injuries from a trauma
- neurometabolic diseases
- severe infections that lead to neurological impairments
There is no cure for Rett syndrome. Any treatments offered only attempt to help manage symptoms, not cure the condition. Examples of treatments that may be used include:
- breathing treatments or assistive devices
- medication to manage motor disorders, tremors, or spasticity
- anticonvulsant medications for seizure control
- heart monitoring
- regular spinal and neurological checkups
- occupational therapy
- physical therapy
- mobility devices, such as braces or splints
- nutritional therapy or feeding assistance
- academic and social support services
A multidisciplinary approach is usually needed, but exact treatments will depend on specific symptoms and severity.
The rarity of Rett syndrome makes it difficult to really estimate life expectancy. As treatments for the symptoms of this disorder improve, so do lifespan expectations.
Females with Rett syndrome typically have a:
- 100 percent chance of reaching age 10
- 90 percent chance of reaching age 20
- 75 percent chance of reaching age 30
- 65 percent chance of reaching age 40
- 50 percent chance of reaching age 50
There are several measures someone can take to improve life expectancy. These include getting good nutrition, having close care and supervision, and regular heart monitoring.
About a quarter of all deaths in people with Rett syndrome are sudden and unexpected. This is possibly due to unknown issues with the electrical system of the heart.
Rett syndrome is a genetic disorder that appears in infancy and leads to significant physical and mental disabilities. This condition mostly affects females, but it’s still rare, affecting only about 1 in 10,000.
For females and families dealing with this condition, close supervision and regular healthcare is key to living into adulthood. Symptom management and a strong support team can help people through the stages of Rett syndrome and may add years of life.