What is Rett Syndrome? Symptoms, Stages, Diagnosis, and Treatment Methods

Rett syndrome is a rare, progressive neurodevelopmental disorder that occurs as a result of mutations in the MECP2 gene on the X chromosome, primarily affecting girls. One of the most notable features of Rett syndrome is that the child shows normal development for the first 6 to 18 months. Following this period, signs of regression begin, such as slowing of head circumference growth, loss of motor skills, decreased eye contact, and cessation of speech. As the disease progresses, various neurological and physiological complications may arise. Although there is currently no definitive cure for the syndrome, research into innovative approaches such as gene therapy is ongoing.

What is Rett Syndrome?

Rett syndrome is a rare neurodevelopmental disorder caused by certain mutations in the MECP2 gene located on the X chromosome. Described by Austrian pediatric neurologist Andreas Rett in 1954 and first appearing in the literature in 1966, Rett syndrome primarily affects girls. Research shows that Rett syndrome occurs in approximately one in every 10,000 to 20,000 live female births worldwide. It is much rarer in males.

The main reason the syndrome is more common in girls is its association with a gene found on the X chromosome. Because boys have only one X chromosome, a mutation in the MECP2 gene is usually so severe that it poses a life-threatening risk while the baby is still in the womb or shortly after birth. In girls, since there are two X chromosomes, the problem in one can be partially compensated for by the other healthy X chromosome.

At this point, a natural process called X-inactivation also has an effect. In girls, one of the two X chromosomes in each cell is randomly deactivated. This leads to the functioning of the mutated MECP2 gene in some cells and the healthy one in others. This explains why the severity of the disease can vary from person to person. Research shows that most MECP2 mutations occur randomly in the father's sperm cells. Therefore, Rett syndrome often appears completely unexpectedly, without familial transmission.

What Are the Symptoms of Rett Syndrome?

Symptoms of Rett syndrome are generally not apparent in the first months of life. Most babies go through a healthy developmental process for the first 6 to 18 months. They show age-appropriate progress in motor, social, and communication skills, but after this period, noticeable changes in development begin to emerge. These symptoms, which are initially vague and mild, can become more pronounced over time. For this reason, experts divide the syndrome into 4 stages to evaluate it clinically.

Accordingly, the stages and symptoms of Rett syndrome are as follows:

Early-onset stagnation stage (Stage I): This stage is usually seen between 6 months and 1.5 years of age. During this period, parents, especially mothers, notice a sudden change in their baby's interaction. Babies may demand less attention from their mother and may become more irritable and restless. Most parents think this is related to the baby's teething process. During this period, the baby's postural development continues, but not as rapidly as before. For example, although they may learn to sit, they may not learn positions such as crawling or standing. Therefore, moving on the buttocks is common in most babies with Rett syndrome characteristics. Since the development of babies is still normal during this period, it can be difficult to make a diagnosis.

Rapid developmental regression stage (Stage II): Starting between 1 and 4 years of age, this period is one of the most prominent and noticeable phases of Rett syndrome. Children experience a rapid and significant regression in previously acquired speech, hand skills, social interaction, and motor abilities. Families usually first notice symptoms such as the child's decreased eye contact, loss of interest in playing, and lack of communication. In some cases, symptoms such as loud crying, fever, lethargy, and apathy appear in the child. Additionally, significant changes are seen in hand movements and purposeful movements in stage II Rett syndrome. Children begin to perform movements such as hair pulling, head banging, and meaningless hand clapping. Sleep problems, night crying, recurrent fever, breathing issues, twitching at the corners of the lips, and grimacing are also frequently seen. At the same time, a regression in head growth is noticeably apparent in the vast majority of children. Additionally, language problems in Rett syndrome also emerge significantly at this stage. Children may stop learning new words and speaking.

Pseudo-stationary stage (Stage III): This stage begins with the end of the regression process. If the child has previously learned to walk, they may maintain this skill. Some may learn to walk at this stage. The loss of purposeful hand use is now evident. The most notable feature is the onset of repetitive hand movements. As soon as they wake up, children may perform constantly repeating movements such as wringing, washing, clapping, or rubbing their hands on different parts of their body. During this period, eye contact increases again, and the child may become more alert and interested. Respiratory problems, which were relatively present in Stage II, are more pronounced in this stage. Rapid breathing, breath-holding, and sudden moments of vacancy (non-epileptic staring spells) become more frequent. Night insomnia, night laughing, and excessive daytime sleepiness may be seen. Scoliosis (curvature of the spine) is a common and rapidly progressing problem at this stage.

Late motor deterioration (Stage IV): Characterized by the patient's loss of the ability to walk, this stage usually begins at age 10 and beyond. Some children transition directly from Stage II to Stage IVB without ever walking. Stage IVB of Rett syndrome is generally characterized by severe muscle wasting, loss of muscle strength, deformities in the hands and feet, and limb deformities. Repetitive hand movements become less intense and simpler as age progresses. Long-term immobility can lead to the development of excessive stiffness and loss of flexibility in the muscles over time.

Despite the aforementioned, the ability to communicate through eye contact and eye signals is generally preserved in individuals with Rett syndrome. Therefore, Rett syndrome is a health issue where families and caregivers must carefully follow the cues given by the eyes when communicating with the child.

How is Rett Syndrome Diagnosed?

Rett syndrome is usually diagnosed through physical examination and genetic tests after the child's developmental delay is noticed. Families often consult a specialist when they realize that their child's development has stalled and they have begun to lose learned skills. Doctors first ask families some questions to evaluate the child's birth, developmental process, and family history in detail. Then, they evaluate the child's general health status in detail.

They investigate symptoms that might suggest Rett syndrome, such as repetitive hand movements, head circumference, and language problems. They may request various tests to rule out other health problems that could cause similar symptoms. Today, it is possible to detect the mutation in the MECP2 gene with genetic screening tests, but in some cases, if the test result is negative but the symptoms suggest Rett syndrome, doctors may recommend additional genetic tests to investigate different gene mutations.

How is Rett Syndrome Treated?

Rett syndrome is a very rare disorder worldwide, including in Turkey. There is currently no definitive method for the treatment of Rett syndrome. Therefore, experts generally focus on symptoms during the treatment process. For example, if Rett syndrome causes serious complications such as heart or lung problems, the health issue that could pose a life-threatening risk must be treated first. In addition, some medications can minimize seizures and movement difficulties today. At the same time, Rett syndrome is a health issue that requires special education. Methods such as speech therapy and occupational therapy can help improve motor and language skills in children.

Rett syndrome treatment methods are carried out within a multidisciplinary approach. Some methods that help alleviate the symptoms of Rett syndrome can be listed as follows:

Regular monitoring of health problems such as scoliosis, digestive system problems, and heart problems,

Medications that can help with seizures, muscle stiffness, or breathing and sleep problems,

Physical therapy,

Nutritional support.

Early-started Rett syndrome education and therapies can enable the individual to participate more easily in school, work, and social activities.

Frequently Asked Questions

While it was previously thought that there was a relationship between Rett syndrome and autism, this is not accepted today. Since research conducted in 1999 linked Rett syndrome to a genetic mutation, Rett syndrome is no longer evaluated under the autism spectrum disorder umbrella. Today, there is no definitive cure for Rett syndrome, but some medications can help alleviate symptoms. Furthermore, the quality of life of individuals with Rett syndrome can be significantly improved with support programs such as speech therapy, occupational therapy, and physical therapy. Although it is possible to understand some congenital anomalies while in the womb, it is difficult to detect Rett syndrome in the womb, as it does not show symptoms even immediately after birth. Language problems are common in patients with Rett syndrome. Some patients may lose the ability to speak entirely. Conversely, therapy programs such as speech therapy can help patients regain their ability to speak.

If you would like to get more information about Rett syndrome and receive support from our specialist physicians for your diagnosis and treatment process, you can contact our Hisar Hospital Intercontinental Neurology department immediately. Early evaluation is of critical importance in improving the quality of life of children.