Rett syndrome

Rett syndrome (also known as Rett syndrome) is a rare neurodevelopmental disorder that affects brain and nervous system development, usually in girls. Rett syndrome usually manifests in early childhood, usually between 6 and 18 months of age. The condition is named after Austrian physician Andreas Rett, who first described the condition in 1966.

The main characteristics of Rett syndrome include:

1. Loss of skills: Children with Rett syndrome usually start life as seemingly normally developing children, but then between 6 and 18 months of age there is a loss of previously developed skills and deterioration in motor and communication skills.
2. Stereotypical motor movements: Children may exhibit stereotypical motor behaviors such as handedness as well as other involuntary movements.
3. Communication difficulties: They may lose the ability to communicate and stop speaking or using words to communicate.
4. Social isolation: Children with Rett syndrome may suffer from social isolation and difficulty connecting with others.
5. Behavioral and emotional problems: Rett syndrome can be accompanied by aggression, anxiety, irritability, and other emotional and behavioral problems.

Rett syndrome is usually caused by genetic mutations, the main gene associated with this syndrome is MECP2. However, it can manifest randomly without an inherited predisposition.

Treatment for Rett syndrome aims to relieve symptoms and improve patients' quality of life. This may include physical and speech therapy as well as medication to manage symptoms. Parent and family support also plays an important role in the care of children with Rett syndrome.

Epidemiology

Rett syndrome (Rett syndrome) is a rare neurodevelopmental disorder and its prevalence is quite low. Epidemiological data may vary slightly from region to region, but in general the following facts characterize its prevalence:

1. Gender and race: Rett syndrome occurs mostly in girls. This disorder is due to mutations in the MECP2 gene, which is located on the X chromosome. Therefore, boys are usually missing one X chromosome, while girls have two, which can partially compensate for the mutation. Women with a mutation in the MECP2 gene may show symptoms to varying degrees.
2. Rarity: Rett syndrome is considered a rare disorder. Its exact prevalence can vary, but the general rate is about 1 case per 10,000 to 15,000 live-born girls.
3. Genetics: Most cases of Rett syndrome are due to new mutations in the MECP2 gene and are not associated with an inherited pathway. It occurs randomly.
4. Age of onset: Symptoms of Rett syndrome usually begin to appear between 6 months and 2 years of a child's life.

It is important to note that Rett syndrome can present in varying degrees of severity, and some children may have a milder form of the disorder. Epidemiologic data are being researched and updated as modern diagnostic techniques and molecular genetics allow for more accurate identification of cases of the disorder.

Causes of the rett syndrome

The main cause of Rett syndrome is changes in the MECP2 (methyl-CpG-binding protein 2) gene, which is located on the X chromosome. This mutation can occur by chance during fetal development and is not inherited from the parents.

Rett syndrome usually occurs in the background of a MECP2 mutation, which can include various changes in the gene such as deletions, duplications, insertions, and others. These changes in the MECP2 gene affect the development of the nervous system and brain.

It is important to note that Rett syndrome is much more common in girls than in boys. This is because the MECP2 gene is on the X chromosome, and boys have only one X chromosome. Girls, on the other hand, have two X chromosomes, and a mutation in one of them can be partially compensated for by a normal X chromosome.

The exact mechanisms by which a mutation in the MECP2 gene leads to the symptoms of Rett syndrome are still being investigated, but it is believed to be related to an impaired function of this gene in brain development and function.

Risk factors

Rett syndrome is caused by a genetic mutation and most often occurs randomly due to new changes in the MECP2 gene, which is located on the X chromosome. Thus, the main risk factor is the child's position in relation to the mutated X chromosome and the randomness of this mutation. However, there are several factors that can increase the risk of Rett syndrome:

1. Sex Chromosome: Rett syndrome is much more common in girls than boys because the MECP2 gene is on the X chromosome. If a male has a mutation in this gene, it can be fatal because males have only one X chromosome.
2. Genetic factor: If one parent has a mutation in the MECP2 gene, there is a small risk of passing this mutation to the offspring. However, in most cases, Rett syndrome occurs as a new mutation that occurs by chance during embryonic development.
3. Heredity: Although Rett syndrome is not inherited from parents in the traditional sense, sisters and daughters of girls with the syndrome have a small increased risk of also having a mutation in the MECP2 gene.
4. Family history: If there is already a family history of Rett syndrome, this may increase concern that there is a genetic risk.

It is important to note that Rett syndrome is a rare disorder, and most children with this syndrome have a randomly occurring mutation in the MECP2 gene, independent of the presence of risk factors.

Pathogenesis

The pathogenesis of Rett syndrome is associated with a mutation in the MECP2 gene, which encodes the methyl-CG-binding protein 2 (MECP2) protein. This protein plays an important role in regulating the activity of other genes, controlling DNA methylation and ensuring the normal functioning of the nervous system.

In Rett syndrome, a mutation in the MECP2 gene leads to deficient or abnormal activity of the MECP2 protein. This affects many genes and biological processes in the brain, including neuronal development and function.

The main characteristics of Rett syndrome are:

1. Regression: Children with Rett syndrome usually develop normally for the first few months of life, but then begin to experience regression and loss of skills, including speech, motor skills, and social interaction.
2. Stereotypical hand movements: Children with Rett syndrome often exhibit stereotypical hand movements such as shaking, flapping, and rubbing. These movements are one of the hallmarks of the syndrome.
3. Character traits: Children may exhibit autistic traits such as limited interaction with others and communication disorders.
4. Developmental delay: Rett syndrome is accompanied by delays in motor, coordination, and psychomotor skills.

As the disease progresses, brain function deteriorates, leading to severe impairments in behavior and functional skills.

Symptoms of the rett syndrome

The symptoms of Rett syndrome can be varied and change over the course of a patient's life. The main signs of this syndrome include:

1. Regression: Children with Rett syndrome usually develop normally for the first 6 to 18 months of life, but then begin to lose previously acquired skills. This process may include loss of motor skills as well as impaired speech and social functioning.
2. Stereotypical hand movements: One of the characteristic signs of Rett syndrome is stereotypical hand movements. This may include shaking, rotational movements, flapping, rubbing, wiping, and other atypical hand movements.
3. Limited communication: Patients with Rett syndrome may have limited communication skills. They may stop using words to communicate and instead show communication through gestures, facial expressions, and other non verbal ways.
4. Loss of interest in the world around them: Children with this syndrome often lose interest in toys, the world around them, and socializing with others.
5. Sleep disorders: Sleep may be disturbed, including insomnia and nighttime sleep disturbances.
6. Motor problems: Patients may have coordination and motor difficulties, making it difficult to perform simple daily tasks.
7. Certain physical features: Some children with Rett syndrome may have physical features, such as small head size (microcephaly) and reduced height.
8. Hypersensitivity to stimuli: Patients may exhibit hypersensitivity to noise, light, and other environmental stimuli.

The symptoms of Rett syndrome can vary significantly from patient to patient, and their severity can change over the course of a lifetime. The disease is progressive and patients' condition worsens over time.

Stages

There are usually four main stages of Rett syndrome:

1. Primary stage: This stage begins in early childhood, usually between 6 months and 2 years of age. Children in this stage usually develop normally for the first few months of life, but then begin to lose previously acquired skills. This may include deterioration in motor skills, social functioning, and speech.
2. Regressive stage: This stage is characterized by dramatic regression of the patient. Children may lose the ability to walk, talk, and interact with the world around them. Stereotypical hand movements and "praying-style" arm movements may become characteristic.
3. Plateau: As children enter a plateau, the rate of deterioration slows. Symptoms become more stable and the duration of this stage may vary.
4. Level of Stability: In the final stage of Rett syndrome, symptoms remain stable and patients may continue to require ongoing medical monitoring and care.

These developmental stages may have individual variations, and periods of plateau and stability may differ for each patient. В

Forms

Rett syndrome has several forms, but the main forms are the classic form and the atypical form. Here are their main characteristics:

1. Classic form of Rett syndrome:

   • Characterized by the onset of symptoms in early childhood, usually between 6 months and 2 years of age.
   • Children begin to lose previously acquired skills in motor activity, social adaptation and communication.
   • Stereotypical hand movements such as shaking, splashing, and repeatedly rubbing the hands appear.
   • Characteristic symptoms include loss of speech or the development of aphasia (loss of the ability to speak), sleep disturbances, and aggressive and hostile behavior.
   • Most cases of the classic form of Rett syndrome are associated with mutations in the MECP2 gene.

2. Atypical form of Rett syndrome:

   • This form of the syndrome has less typical manifestations and the onset of symptoms may be at an older age, sometimes in adolescence or adulthood.
   • Symptoms may be less severe and not as stereotyped as in the classic form.
   • Mutations in the MECP2 gene can also cause an atypical form of Rett syndrome, but they can be different in nature.

Complications and consequences

These complications and consequences can vary depending on the severity of the syndrome and the effectiveness of care and rehabilitation. Here are some of the possible complications and consequences:

1. Loss of motor skills: Children with Rett syndrome often lose previously acquired motor skills. This can lead to poor motor coordination and loss of independence.
2. Speech loss: Many children with Rett syndrome lose their speech or develop aphasia (impaired ability to speak). This makes communication and social interaction difficult.
3. Stereotyped movements: Characteristic features of Rett syndrome are stereotyped hand movements such as shaking, splashing and repeatedly rubbing the hands together. These movements may be involuntary and can create difficulties in daily life.
4. Social isolation: Due to impaired communication and social interaction, patients with Rett syndrome may experience social isolation and difficulty establishing relationships with others.
5. Oral Health Problems: Uncontrolled salivation and frequent hand motions can create oral health difficulties, such as possible gum and dental problems.
6. Scoliosis: Some patients with Rett syndrome may develop scoliosis (torticollis).
7. Eating problems: Patients with Rett syndrome may have difficulty eating due to loss of eating and chewing skills.
8. Increased risk of seizures: Some children with Rett syndrome may have an increased risk of seizures.

Diagnostics of the rett syndrome

Diagnosis of Rett syndrome usually involves the following steps:

1. Clinical examination and history: The physician will interview the patient's parents or guardians to obtain a medical and family history. The clinical examination may also include an assessment of the child's physical and psychomotor development.
2. Diagnostic criteria: Certain clinical criteria approved by the World Health Organization (WHO) are used to establish the diagnosis of Rett syndrome. These criteria include loss of handwriting ability, loss of social skills, stereotyped hand movements, and the mandatory presence of a mutation in the MECP2 gene.
3. Genetic testing: To confirm the diagnosis of Rett syndrome, genetic testing is performed to detect a mutation in the MECP2 gene. This is one of the key criteria for diagnosis.
4. Additional tests: Your doctor may order additional tests such as neurophysiology tests, neuroimaging, magnetic resonance imaging (MRI), or electroencephalography (EEG) to rule out other medical problems or complications.

If Rett syndrome is suspected, it is recommended to see a physician specializing in neurodevelopmental and genetics for a comprehensive evaluation and accurate diagnosis. Early diagnosis allows rehabilitation and support for the patient to begin as early as possible.

Differential diagnosis

The differential diagnosis of Rett syndrome involves distinguishing this condition from other neurological and psychiatric disorders that may exhibit similar symptoms. It is important to perform a comprehensive examination and consider the following possible diagnoses:

1. Pediatric Autism: Rett syndrome and autism may share some similarities in clinical manifestations, including social isolation and impaired communication skills. However, Rett syndrome usually begins with normal development and involves loss of skills, whereas autism manifests from the beginning of life.
2. Pediatric catatonic syndrome: It is a psychiatric disorder that may be accompanied by stereotyped movements and social isolation.
3. Childhood Disintegrative Disorder: This is a rare disorder in which a child loses skills that were previously acquired. It may resemble Rett syndrome in its symptoms.
4. Epilepsy: Some forms of epilepsy may manifest with stereotyped movements and impaired psychomotor development.
5. Other neurodegenerative disorders: In some cases, the symptoms of Rett syndrome may be similar to other neurodegenerative diseases such as Hunt's disease, acerulinemia, or Krabbe disease.

Genetic testing and additional testing under the guidance of an experienced neurologist or geneticist are critical for an accurate differential diagnosis. Establishing an accurate diagnosis is essential for proper treatment and patient support.

Treatment of the rett syndrome

Rett syndrome treatment is aimed at managing symptoms and improving the patient's quality of life. It is important to note that Rett syndrome is a neurodegenerative disorder and a complete cure is not currently possible. Treatment typically includes the following components:

1. Drugtherapy: Medications may be used to manage some of the symptoms of Rett syndrome, such as epileptic seizures, aggressive behavior, and sleep disturbances. For example, antiepileptic drugs, antidepressants, and other medications may be prescribed depending on the specific needs of the patient.
2. Physical therapy and rehabilitation: Physical therapy and orthopedic techniques can help support physical development and improve movement coordination.
3. Speech therapy and speech therapy: These methods help improve communication skills and the ability to communicate.
4. Support and education: Psychological and social support is available for patients and their families. Educational programs can help families better understand and learn to cope with Rett syndrome.
5. Adaptive technology: The use of various technological tools, such as specialized apps and communicators, can improve communication abilities in patients with Rett syndrome.
6. Genetic therapies and clinical trials: Research and clinical trials may provide new treatments in the future because Rett syndrome is associated with gene mutations. Various genetic therapies are currently being investigated.

Treatment for Rett syndrome should always be individualized and tailored to the specific needs of the patient. The treatment plan is tailored to the clinical picture and coordinated with the neurologist and other specialists. It is important to provide the patient with maximum support and quality of life within their capabilities.

Prevention

Rett syndrome is a genetic disorder and its occurrence is due to mutations in genes. Therefore, there is no prevention of the syndrome as such. It can develop in children who have the relevant genetic mutations.

However, genetic counseling and testing can be helpful for families who have a history of Rett syndrome or other similar genetic conditions. If a family already has a child with Rett syndrome, genetic counseling can help them understand the risk of passing this mutation to future children.

Forecast

The prognosis of Rett syndrome can vary greatly depending on the severity of symptoms and the availability of medical support. Rett syndrome is usually not fatal, and most children affected survive into adulthood. However, quality of life and prognosis can vary greatly:

1. Mild cases: Some children with Rett syndrome have milder symptoms and are able to perform basic daily tasks independently. They may have a better prognosis and can lead a more independent lifestyle.
2. Severe cases: Some children with Rett syndrome have more severe symptoms and require ongoing medical and social support. In these cases, quality of life can be significantly reduced.

It is important to note that Rett syndrome can manifest in different ways in different children, and each case is unique. Medical and rehabilitation support, as well as early intervention and therapy, can significantly improve the prognosis and quality of life for children with this syndrome. The earlier treatment and rehabilitation begins, the better results are usually achieved.

Literature used

Gusev, Ababkov, Konovalov: Neurology. National manual. Volume 1. GEOTAR-Media, 2022.

Ginter, Puzyrev, Skoblov: Medical Genetics. A national manual. GEOTAR-Media, 2022.