Rett syndrome: description, symptoms, treatment methods

General information about pathology

What is it, and how long do children with this syndrome live? Rett syndrome - photo:

Rett syndrome belongs to psychoneurology and was discovered in 1954 . Early manifestations of this pathology are similar to the symptoms of autism, so when diagnosing it is important to compare information and accurately make a diagnosis.

The disease occurs predominantly in girls , since its development is associated with the X chromosome. Girls with the disorder survive because they have two X chromosomes, while boys with the same disorder die before birth.

Rare cases of diagnosed Rett syndrome in boys are associated with Klinefelter syndrome , in which the boy has an extra X chromosome. Also, male children may develop atypical varieties of this pathology, but cases of incidence are extremely rare.

The pathology is considered common: out of 10-15 thousand girls born, one is a carrier of Rett syndrome.

Reasons for appearance

The development of pathology is based on a mutation in the MECP2 gene , which is located on the X chromosome.

Its expression is interrupted and it stops functioning correctly.

If this gene is normal, during a certain period of brain formation it blocks the activity of a number of other genes , and the brain continues its full development.

If the structure of the gene is disrupted, it does not perform this function, and the brain is formed incorrectly, which leads to progressive mental retardation and other severe symptoms.

More than 70% of cases of pathology are associated with disorders in the genetic material of the child’s father.

Symptoms and signs

When a girl with Rett syndrome is born, she has no visible problems . Basic indicators - weight, general appearance, head circumference - are normal, and if there are abnormalities, they are not associated with Rett syndrome.

For the first three to four months, the child develops in the same way as his peers. At this stage, only muscle weakness is noted, and the following symptoms are also observed:

• low body temperature;
• pronounced sweating in the area of ​​​​the feet and palms;
• pale skin.

When a child reaches six months, he shows signs of a lag in the development of movement skills (crawling, rolling over on his back). He begins to sit and stand late, does not show any expressed interest in toys, and is apathetic.

Signs of pathology may be absent during infancy and appear later.

The progression of Rett syndrome is divided into four stages:

1. Stage I. At the very beginning of life, the child develops at a normal pace, no serious disturbances in his development are noted. It is even possible that the initial stage will occur a year or two after birth: the first symptoms of Rett syndrome are observed between 6 months and 2.5 years of life. The child’s motor development slows down, he becomes uninterested in playing, and is indifferent to toys and activities that were previously interesting. Muscle tone falls, deviations in physical development are observed: the head grows more slowly, the process of lengthening the tubular bones also slows down, and the child looks shorter and weaker than his peers. Cardiovascular diseases and disruptions in the functioning of the gastrointestinal tract may also occur.
2. Stage II. This stage of the disease is observed 1-2 years after the onset of the first symptoms. The first signs of transition to the second stage are the occurrence of sleep disturbances (insomnia, frequent awakenings, poor sleep), the child looks anxious. After this, children quickly, within a few weeks, lose almost all previously acquired skills, stop walking, talking, and cannot hold objects in their hands. At this stage, respiratory disorders occur: apnea (cessation of respiratory activity), lasting for 1-2 minutes, is replaced by hyperventilation, when the child breathes deeply and frequently. These abnormalities in breathing processes are observed when the child is awake and disappear during sleep.

Other pathologies are also observed: epileptic seizures, poor coordination, and repetitive movements characteristic of this disease, reminiscent of hand washing.

3. Stage III. The progression of symptoms slows down.
   Children have severe mental retardation, mastering new skills is extremely difficult, and epileptic seizures often occur, which are difficult to control. Muscle spasms and involuntary motor activity (hyperkinesis) are also observed. But some symptoms may disappear: sleep improves, anxiety levels decrease, the child looks calmer, and interaction with parents and attending physicians becomes easier. This period on average begins at 2-4 years and ends at 10-15 years.
4. Stage IV. The number of epileptic seizures is reduced, they may disappear completely, but there is a rapid progression of motor abnormalities. Most children at this stage almost completely lose the ability to move, the muscular system atrophies, and damage to the blood vessels of the legs occurs, which increases the likelihood of ulcers due to problems with blood supply. The spinal column is severely curved due to muscle atrophy. This stage lasts for the rest of your life.

Symptoms characteristic of each stage may vary and are closely related to the individual characteristics of the child and the rate of progression of the pathology.

Rett syndrome

Rett syndrome is an extremely rare hereditary disease that occurs in girls mainly at an early age, characterized by regression of psychomotor development, autistic-like behavior, loss of purposeful hand movement skills, and epileptic seizures [1]. The frequency of occurrence is usually 1:15000 [3].

This disease was first described in the literature of the second half of the twentieth century, when the Austrian pediatrician Addressass Rett, while studying a group of girls from different European cities, described the syndrome, which is manifested by a progressive loss of mental and motor skills [1].

From the notes of the pediatrician himself: “It was in February 1965 when I saw two mothers holding their children on their laps in a doctor’s waiting room. Both children swayed from side to side as their mothers held their hands tightly. I knew both girls very well who were currently undergoing examination. That morning, as usual, I passed by them, and suddenly the mothers released the hands of their children. The girls immediately linked them together and, as if on command, the two of them began to make the same “washing” movements. These were the same straight looks, the same facial expressions, the same weak muscles and stereotypical movements. I asked the women not to restrict their children’s movements anymore and was surprised by the idea that dawned on me...” [1]

Rett syndrome occurs as a result of a disorder of brain development, which is caused by a mutation in the MECP2 transcription gene, associated with the X chromosome, located at the Xq28 locus [2]. To date, 8 mutations of this gene have been identified. It is assumed that the MECP2 gene controls the development of the central nervous system. It is important to note that mutations of this gene can also occur in boys, but such individuals in the population are not viable and die in the first hours of life [1,2].

According to the latest results of neurophysiological studies, in Rett syndrome there are disturbances in the synaptic organization, as well as disturbances in dopamine metabolism, and atrophic changes are detected in the rostral parts of the cerebral cortex (RCC), which occur in the early stages of ontogenesis [2]. Atrophic changes are also found in the nucleus caudatus, substantia nigra. Disturbances in the development of CGM are manifested by gross dysfunction of the frontal lobes of the brain with loss of their organizing influences. Deafferentation and disinhibition of hierarchically lower parts of the cortex and subcortical structures occur, which leads to regression of psychomotor development with age [1,2].

The disease manifestation interval is from 6 to 20 years; in extremely rare cases, the first symptoms are detected before the age of 3 months. An important pathognomonic sign is normal psychomotor development before the onset of the disease [2]. Nonspecific symptoms are: congenital hypotonia, hypomimia, delay in the acquisition of motor skills, weak sucking, monotonous inconsolable crying, emotional rigidity, problems with fixation of gaze [3].

Clinically, Rett syndrome is divided into four stages [2].

1. The first stage or stage of stagnation. Duration is from 2 to 4 months, rarely more. At this stage, psychomotor development stops and the growth rate of the head, bones and feet slows down. Muscle hypotonia appears, interest in games and the surrounding world disappears, and visual concentration is impaired. At this stage, a clinical diagnosis cannot be made [1].

2. Second stage or stage of rapid regression. During this period, regression of psychomotor development occurs with a gradual loss of previously acquired skills. The leading symptoms are the loss of purposeful manual activity and the appearance of special stereotypical motor acts. This symptom is pathognomonic [1,2]. Stereotyped motor acts include: “washing” movements with hands, twisting of hands, rubbing hands against each other, as well as knocking teeth, grinning, chewing movements. Children may develop babbling speech or individual words [3]. However, in the second stage of the disease, there is a complete loss of expressive speech, and children are able to produce only individual sounds. Patients often scream and have trouble falling asleep. A similar picture most often forms before the age of three. Life expectancy is several months [1,2].

3. Third stage (pseudo-stationary). It is characterized by relative stagnation in the development of the disease. Symptoms of autistic behavior decrease, anxiety attacks disappear, and sleep normalizes. At this stage, disturbances of gnosis and praxis clinically prevail, stereotypies in the hands and the absence of purposeful manual activity persist. Signs of disturbances in the conduction of nerve impulses along the pyramidal tract, static and dynamic ataxia, muscular dystonia, and tremor are revealed [1,3]. This stage of disease development is characterized by 3 types of paroxysmal conditions: episodes of hyperventilation, syncope and epileptic seizures [3].

4. The fourth stage or stage of late motor disorders. This stage is characterized by the progression of the development of motor disorders and, as a rule, appears closer to 10 years. Paresis worsens, the severity of spastic-amyotrophic syndrome increases. Muscle rigidity in the lower extremities is clearly visible. The degree of scoliosis and kyphoscoliosis increases. By the age of 15, a child is not able to walk independently [1].

The main method of objective study of this disease is EEG. It is characterized by a slowdown in the main background recording activity [1]. In this case, signs of epilepsy appear on the EEG in the form of “peak-wave”, “sharp” wave complexes, and slow “sharp-slow” wave complexes long before the attacks themselves. MRI shows a decrease in brain volume, mainly due to a decrease in white matter, and atrophic changes in the caudate nucleus [1].

Table 1 |
Diagnostic criteria for typical Rett syndrome [1]

Table 2 | Diagnostic criteria for atypical Rett syndrome [1]

The main goal in the treatment of Rett syndrome is the control of epileptic seizures. The best drugs for these purposes are carbamazepine, lamotrigine, and topiramate [1]. .

Sources:

1. K.Yu. Mukhin. Rett syndrome / K.Yu. Mukhin, V.I. Karpova, I.S. Bezrukova // Russian Journal of Child Neurology - 2020 - No. 10 - P. 43–51
2. I.Yu. Yurov. Complex clinical and genetic approach to the diagnosis of Rett syndrome in children / I.Yu. Yurov, S.G. Vorsanova, V.Yu. Voinova-Ulas, P.V. Novikov, Yu.B. Yurov // Russian Journal of Pediatrics - 2012 - No. 6 - P. 38–43
3. O.V. Timutsa. Rett syndrome: socio-psychological aspect of the problems of people with rare diseases / O.V. Timutsa, V.D. Mendelevich // Neurological Bulletin - 2013 - No. 2 - P.60-65

Diagnostics

Primary diagnosis is carried out based on the child’s medical history, complaints and other information provided by parents. Due to the similarities between Rett syndrome and autism, differential diagnosis is necessary.

Differences between Rett syndrome and autism:

General diagnostics are also carried out, which includes the following studies:

1. MRI of the brain. Using this method, one can notice a decrease in brain volume and its smoothness.
2. Electroencephalogram. There is a decrease in background brain activity, the reaction to stimuli is weakly expressed.
3. Molecular karyotyping. Allows you to detect abnormalities in the gene associated with the development of the disease.
4. Ultrasound of the liver and spleen. 20-30% of children with this disease have underdevelopment of these organs.

Diagnosis of Rett disease

Only a doctor can determine whether a child has a disease: parents should not treat their child based on guesswork. Diagnostics occurs in several stages:

1. Conversation with the mother and father of the child. First of all, the doctor identifies a hereditary connection, therefore, during the first appointment, parents must be informed whether the baby’s relatives or they themselves have Rett syndrome;
2. Next, the child's reflexes are checked. The syndrome is characterized by a complete absence of elementary reflexes;
3. A computed tomography scan is performed. The results of the procedure will make it clear whether there are any disturbances in the development of the baby’s central nervous system;
4. An electroencephalogram is performed. This study will help check the biological activity of the brain and the presence of possible pathologies.

Based on the results of these procedures, the doctor makes a verdict. If suspicions are confirmed, he prescribes appropriate treatment.

Treatment and rehabilitation

There is currently no cure for Rett syndrome, but research is underway that shows that over time it will be possible to change the defective gene and the symptoms will disappear.

To improve the child’s condition, medications are used to eliminate or reduce the severity of certain symptoms:

• anticonvulsants (Carbamazepine, Valparin). Due to the characteristics of the disease, anticonvulsant medications show low effectiveness;
• nootropics (Phenibut, Cerebrolysin, Actovegin). Improve learning ability, have a beneficial effect on cerebral blood supply;
• stimulators of dopamine D2 receptors (Bromocriptine, Tolcapone). Positively affect motor skills;
• sleeping pills (Trazodone, Melatonin).

Depending on the symptoms, medications may be prescribed to treat diseases of the heart, liver, and spleen.

Rehabilitation measures include:

1. Massage. Improves muscle tone, has a calming, relaxing effect, and has a beneficial effect on motor skills.
2. Therapeutic gymnastics. Physical activity allows you to maintain some muscle tone, improve motor skills, and has a positive effect on the emotional state of the child.
3. Various therapeutic practices. Music therapy shows good results: the child becomes more emotional, balanced, more sociable, and the level of anxiety decreases. If epileptoid activity is absent, Tomatis therapy can be used, when the child listens to special music that has a beneficial effect on his brain activity. Hippotherapy, hydrotherapy, art therapy, and ABA therapy are also used.
4. Working with a defectologist, psychologist, osteopath. A psychologist and speech pathologist help the child improve communication skills and motor skills. Osteopathy has a positive effect on the condition of the spine.

Read about methods for correcting minor cerebral dysfunction in children here.

Treatment

Today, Rett syndrome is an incurable disease. But with the help of specially selected medications and a therapeutic diet, significant improvements can be achieved and various body deformations can be prevented.

Drug treatment

To relieve symptoms, the child is prescribed the following medications:

• Antiepileptic drugs. Drugs in this group help reduce the number of attacks (Lamotrigine, Carbamazepine, etc.).
• Nootropic drugs. These medications are necessary to improve brain function (Cerebrolysin, Cortexin, Nootropil, etc.).
• Sedatives that provide behavior correction (Glycine, Phenibut, etc.).
• Antiparkinsonian drugs (Parlodel, Bromocriptine, etc.).

To regulate the daily regimen, patients are prescribed Melatonin, as well as drugs to support the functioning of internal organs (for the heart, liver and gastrointestinal tract).

Treatment medications are available only with a doctor's prescription. In addition, they are not recommended to be taken without consulting a doctor.

Nutrition

Children with Rett syndrome are often underweight, so their diet should be rich in fat. So, the diet must contain vitamins and fiber (meat products, fish, boiled or stewed vegetables, cereals, etc.). You need to eat often (preferably every 3 hours), but in small portions. Dishes should be served chopped or grated. This diet will help avoid sudden weight loss and strengthen the patient’s condition.

Features of care and education

Nutritional features for Rett syndrome:

1. Food should be given in crushed form . The child has difficulty chewing and eats slowly, so if the food is crushed, it is easier to feed him. Porridges, fruit and vegetable purees, soups, juices, yoghurts, and fortified milk are good options.
2. Frequent meals. It is important to feed the child every 3-4 hours in small portions so that he receives enough calories and nutrients, and his gastrointestinal tract copes with stress.
3. Food should contain a large amount of useful substances . A high content of proteins and fats is also important.

If your child has difficulty eating, a feeding tube may be used.

Tips for parents:

1. The moment of realizing the diagnosis is very difficult. If you feel emotionally drained and lose interest in life, then you should see a psychotherapist and communicate more often with friendly people.
2. On the Internet you can find people whose children have been given the same diagnosis, support them, and discuss treatment methods.
3. Remember that your child is still your child, who, like other children, needs careful treatment, love and support. Your actions can improve his life.