Rett syndrome – causes, symptoms, diagnosis, treatment, prognosis

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Rett syndrome is a rare genetic disease that almost exclusively affects women a few months after birth. It’s a neurodevelopmental disorder, which means it affects how the brain, spinal cord, and nerve system and cells that transmit messages between them and the rest of the body function. Rett syndrome causes physical, mental and behavioral problems, as well as epilepsy. Unfortunately, there is no cure for Rett syndrome, but different treatments can help manage the effects of the disease. Children with Rett syndrome are sometimes referred to as “Silent Angels” because of the title of the documentary about the disorder.

Rett syndrome – symptoms

Symptoms of Rett syndrome do not usually occur at birth but begin early in life. The exact age varies from child to child.

Some subtle symptoms may appear before a child reaches 1 year of age, with more noticeable symptoms starting between the ages of 3 and 5. The symptoms of Rett syndrome can range from mild to severe. They can be regressive, which means that the patient loses the previously acquired skills, e.g. stops talking, does not control his hands. Other symptoms can be easily seen when children fail to achieve the physical, cognitive and social skills expected for their age.

Rett syndrome and physical inactivity

Sometimes children with Rett syndrome may not be as physically active as expected at their age. They cannot fall over, use their arms, or kick their legs as actively as typical babies. Physical inactivity may start around age 1 or earlier, although this is not always noticeable. There is usually a decline in activity between the ages of 2 and 5.

See also: Physical inactivity can be treated

Rett syndrome and lack of eye contact

One of the earliest symptoms may be lack of eye contact, which may start before the age of 1. Parents who are not yet familiar with infant behavior may not notice it. Lack of eye contact can be mistaken for a sign of autism.

Rett syndrome and the lack of social interaction

Children with Rett syndrome may lose interest in communicating or other interactions with people, including siblings and parents, and may not be paying attention to others. While they don’t usually show a strong emotional attachment to their parents, children with Rett syndrome can be anxious or scared when their parents are absent.

Rett syndrome and developmental regression

Children may start to learn to speak and, over time, begin to lose their language and communication skills. Sick children may also start using their hands on purpose, but may lose this ability in early childhood.

Rett syndrome and developmental delays

Children with Rett syndrome struggle with learning and motor skills. For example, they may not be able to play video games or understand how to play with puzzles or blocks as children their age do.

See also: Effects of perinatal injuries as a cause of child development disorders

Rett syndrome and the lack of problem-solving skills

Often times, people with Rett syndrome have difficulty learning to solve problems and face small or large challenges with passivity or tantrums.

See also: Anger and anger kill, smile saves lives

Rett syndrome and language disorders

Children with Rett syndrome often communicate at a children’s level of 2 to 3 years of age throughout their lives. They are also only able to understand simple speech and simple commands.

See also: Speech disorders

Rett Syndrome and Loss of Hand Use

Most children with Rett syndrome learn to use their hands and then lose this ability. Despite the fact that they usually maintain normal motor strength, their hand movements become random and uncontrolled rather than deliberate.

Rett syndrome and repetitive movements

As their hand-use skills change, children begin to perform repetitive twisting or squeezing movements. They also often develop other repetitive and pointless movements, such as tapping, clapping, or rubbing.

Rett syndrome and difficulty in movement

Children with Rett syndrome may have difficulty walking and balance. They can stand on their toes when walking or walk with shaky and wide steps with stiff legs.

Rett syndrome and loss of appetite and eating problems

Children may have little or no appetite to eat. In addition, they may have chewing and swallowing problems and may develop symptoms of malnutrition. Occasionally, your baby may be hungry and eat more than usual, or for several weeks, show an increased interest in a certain type of food, but this usually does not last long.

See also: Eating disorders (appetite)

Rett syndrome and differences in physical characteristics

There are several physical symptoms that are common among children with Rett syndrome.

Overall, children with Rett syndrome are shorter, smaller, and weigh less than the average for their age or what would be expected based on their family history. Head circumference is also smaller in children with Rett syndrome.

Such a child may also have lowered muscle tone (hypotonia) and / or a noticeable curvature of the spine known as scoliosis, which can lead to disability with age.

Rett syndrome and sleep problems

Sleep problems are very common in people with Rett syndrome. Young children tend to wake up at night, scream or laugh excessively while sleeping. Older children, on the other hand, are more prone to seizures while sleeping or falling asleep during the day.

Rett syndrome and breathing problems

Often times, a child with Rett syndrome may have episodes of slow or rapid breathing. Usually this is not life threatening. However, in rare cases, a person with Rett syndrome may need artificial ventilation. If a parent is concerned about changes in their child’s breathing patterns, they should talk to their doctor about it.

Rett syndrome and epileptic seizures

Many children with Rett syndrome experience seizures. They may include:

1. generalized tonic-clonic seizures: these include body tremors and usually impaired consciousness with decreased or no response during the seizure. Typically, there is also a period of reduced reaction following a seizure.
2. Absence epilepsy: These are periods of staring and unresponsive. They occur without moving, trembling, or deliberately moving the body. They can occur while a person is sitting or lying down, and can go unnoticed.
3. myoclonic seizures: Characterized by brief jerks of the body, often with some impairment of consciousness.

Your child may experience one or more of these types of seizures and the frequency of these seizures can vary. If a child has seizures, the parent will learn to recognize pre-seizure behavior and symptoms and may be able to prevent seizures with medication.

See also: Epilepsy – causes of seizures and treatment of the disease

Rett syndrome – causes

Rett syndrome is almost always caused by a genetic mutation in the methyl CpG 2 binding protein (MECP2) gene located on the X chromosome.

The mutation is believed to result in a deficiency in protein function. Cells in the brain and other parts of the body cannot perform their normal functions, including communicating properly between the nerves. This causes the common symptoms that characterize Rett syndrome.

The mutation usually occurs randomly. It is inherited or passed down from generation to generation only in about 1% of cases. The syndrome is autosomal dominant, which means that a child only needs to have one X chromosome with the mutation to be affected by the disease.

Girls at birth have two X chromosomes. If one carries the mutation, there is another that will compensate for the error. However, the situation is different in the case of boys who have the X and Y chromosomes. The lack of a “spare” X chromosome makes Rett syndrome more severe in these children.

In rare cases, boys may have a different mutation in the MECP2 gene, which causes intellectual disabilities and developmental problems.

See also: Rett syndrome has to do with moving parts of the DNA

Stages of Rett syndrome development

Rett syndrome has four stages.

1. Stage 1 – Usually starts between 6 and 18 months of age. This stage is often overlooked as the symptoms of the disorder may be somewhat unclear and parents and doctors may not notice a subtle slowdown in development at first. The infant may begin to show less eye contact and have less interest in toys. There may be delays in motor skills such as sitting or crawling. Hand twisting and reduced head growth may occur, but not so much that the child’s caregivers are concerned about this. This stage usually lasts several months but may take more than a year.
2. Stage 2 – Usually starts between ages 1-4 and can last weeks or months. Its onset may be quick or gradual as the child loses hands-on and speaking skills. Characteristic hand movements, such as twisting, rubbing, clapping or tapping, as well as repeatedly moving your hands to your mouth, often start at this stage. The baby can keep his hands clasped behind his back or hold them to his sides every now and then, clenching and unclenching his fists. The movements continue while the baby is awake, but disappear while the baby is asleep. Irregularities in breathing, such as episodes of apnea and hyperventilation, may occur, although breathing tends to improve during sleep. Some girls also show autism-like symptoms such as loss of social interaction and communication. Walking can be unstable and initiating motor movements can be difficult. Slower head growth is usually observed at this stage.
3. Stage 3 – Usually starts between the ages of 2 and 10 and can last for years. At this stage, apraxia, motor problems and seizures are visible. However, there may be an improvement in behavior, with less irritability, crying, and autism-like characteristics. At this stage, greater interest in the surroundings may develop, and alertness, concentration, and communication skills may be improved. Many girls stay in this stage for most of their lives.
4. Stage 4 – can last for years or decades, and usually begins between the ages of 5 and 25. Notable features include decreased mobility, curvature of the spine and muscle weakness, stiffness, spasticity, and increased muscle tone with abnormal arm or leg posture. Children who could walk before may stop walking. Cognitive skills, communication or manual skills are generally not impaired at this stage. Repetitive hand movements may decrease and your eyesight usually improves.

Variations of Rett syndrome

The symptoms of the typical form of Rett syndrome are well described. In addition to the classic form of Rett syndrome, several unusual characters have been described over the years.

1. Odmiana Rolando (Rolando variant): in this severe subtype of Rett syndrome, patients’ development and head circumference are abnormal from birth. The usual gaze of patients with Rett syndrome is usually absent;
2. Odmiana Zappella (Zappella variant): in this subtype of Rett syndrome, patients acquire some manual dexterity and speech skills are partially recovered around age 5. Height, weight and head circumference are often normal and good motor skills can be observed. The Zappella variant is a milder form of Rett syndrome;
3. Odmiana Hanefelda (Hanefeld variant): in this form of Rett syndrome, patients develop epilepsy before 5 months of age.

Rett syndrome – diagnosis

Clinical diagnosis is based on three types of clinical criteria.

1. Major: The main criteria for diagnosing Rett syndrome are the symptoms listed above, such as partial or complete loss of hand skills, loss of prior ability to speak and communicate, repetitive hand movements and / or difficulty walking.
2. Additional: Additional factors, such as lowered muscle tone and genetic test results, may help with diagnosis, but are not required.
3. Exclusive: As part of this process, doctors must definitely rule out other disorders that may produce similar symptoms. A diagnosis of other conditions allows your doctor to rule out Rett syndrome.

Physical examinations in the diagnosis of Rett disease

Your doctor will look for the physical symptoms of Rett syndrome. They will examine and observe your baby for signs of decreased muscle tone. They will also measure and weigh the child and compare the results with expectations for their age and family history; however, there are no numerical values ​​confirming the diagnosis.

Scoliosis can be detected by examining the spine while the child is leaning forward. A tool called a scoliometer is used to measure the amount of torso asymmetry and the angle of rotation in scoliosis. If it is higher than 5 to 7 degrees, scoliosis is confirmed.

These features may not be present in a patient with Rett syndrome, but they do aid in diagnosis.

Genetic tests in the diagnosis of Rett disease

A genetic test can identify a mutation in the MECP2 gene on the X chromosome. This is done with a blood sample.

Having a gene mutation does not confirm Rett syndrome, but it is important in the diagnosis of the disorder. The MECP2 mutation may be present in PPM-X syndrome, neonatal encephalopathy, and autism-like conditions, which are neurodevelopmental disorders that do not meet the criteria for Rett syndrome.

Other research in the diagnosis of Rett disease

Other conditions that may initially appear similar to Rett syndrome include:

1. autism;
2. cerebral palsy;
3. Angelman syndrome;
4. Lennox-Gastaut syndrome (LGS; Lennox-Gastaut syndrome);
5. encephalitis;
6. metabolic disorders in childhood;
7. brain trauma.

Doctors may perform the following tests to rule out such concerns before making a diagnosis of Rett syndrome:

Blood tests and lumbar puncture: Although there are no specific results related to Rett syndrome, blood tests and lumbar puncture are usually performed when symptoms of this disorder are present. These tests can help determine whether an infection or a metabolic disorder may be causing your symptoms.

Neuroimaging: In general, neuroimaging is normal in people with Rett syndrome. Abnormal results may indicate conditions such as encephalitis or brain malformations.

Rett syndrome – treatment

There is currently no cure for Rett syndrome. Treatment is aimed at improving function and relieving symptoms. A multidisciplinary team approach is typically used to treat a person throughout their life. This team may include a primary care physician, physical therapist, occupational therapist, speech therapist, nutritionist, and academic and professional support services. Some children may require special equipment and aids, such as scoliosis arresters, splints to modify hand movements, and nutritional programs to help them maintain a healthy weight.

Treatments for children with Rett syndrome include the following.

1. Taking anticonvulsant medications: There are a number of anticonvulsant medications that may be recommended. The one that may work best depends on the type of seizure being treated. These drugs should be taken regularly. If your child is resistant to taking medication by mouth, you may need to rely on injections.
2. Physiotherapy: Therapy can help improve muscle tone and prevent muscle ulcers and cramps that can develop from lack of exercise.
3. Occupational therapy: This is therapy that helps children learn or try to do independent activities, such as getting dressed and eating meals.
4. Speech therapy: can help families develop means of non-verbal communication as well as work to improve a child’s verbal and social abilities.
5. Treatment of scoliosis: This may include support braces or surgery. Surgery for scoliosis may involve placing a bar to support the spine, which helps prevent mobility problems that may result from scoliosis.
6. Hydrotherapy: Water activities can sometimes help improve hand skills and posture or prolong their mobility.
7. Food supplementation: the combination of low appetite and communication difficulties can result in nutritional deficiencies. You may need to provide your baby with high-calorie dietary supplements, such as smoothies or protein bars, if needed. Occasionally, babies with Rett syndrome may need to temporarily insert a feeding tube to maintain nutrition during bouts of particularly low appetite.

Rett syndrome – prognosis

Men with pathogenic MECP2 mutations usually die within the first 2 years of severe encephalopathy, unless they have one or more extra X chromosomes or have somatic mosaicism.

Male fetuses with this disease rarely survive to delivery. Since the disease-causing gene is located on the X chromosome, a woman born with the MECP2 mutation on her X chromosome has a different X chromosome with an apparently normal copy of the same gene, while a male with the X mutation has no other X but only the Y chromosome; hence there is no normal gene. Without a normal gene that supplies normal proteins in addition to the abnormal proteins caused by the MECP2 mutation, the male XY fetus is unable to slow disease progression, hence many male fetuses with the MECP2 mutation will not survive to delivery.

Women with the MECP2 mutation, however, have an unmutated chromosome that provides them with enough normal protein to survive longer. Research shows that a disorder in men with Rett syndrome may be due to Klinefelter’s syndrome, in which the man has an XXY karyotype. Thus, the unmutated MECP2 gene is essential for the survival of an embryo affected by Rett syndrome in most cases, and an embryo, male or female, must have a different X chromosome.

However, there have been a few reports of males of the 46, XY karyotype with the MECP2 mutation (associated with classic Rett syndrome in females) at term of delivery who were affected by encephalopathy and died before the age of 2 years. The incidence of Rett syndrome in men is unknown, partly because of the low survival of male fetuses with MECP2 mutations associated with Rett syndrome and partly because of differences between symptoms caused by MECP2 mutations and those caused by Rett mutations.

It is assumed that women can live up to 40 years or longer.

See also: The most common genetic diseases. How are they made?

How to deal with Rett syndrome?

If a baby has or may have Rett syndrome, giving birth knows that this is a difficult situation. The child will need help and support in meeting their basic needs throughout their life. Sick children may not show affection and may appear cold and indifferent to their caregivers, while rejecting others who try to enter their lives or provide medical care.

Parents are instructed to work to develop effective communication with their child’s medical team. Often times, clinics – which regularly look after children and adults with neurodevelopmental disorders – have a system for resolving major and minor problems. Your child will also benefit from attending a public or private school that offers additional services during the school day, such as physical therapy or speech therapy. Staying in touch and collaborating with teachers and school assistants is also helpful.

If care becomes more involved and difficult, the parent or guardian may need to find a care facility so that the child can receive professional care on a daily basis. This decision is never easy, but it may turn out to be in the best interests of a sick child.