Rett Syndrome

Classification according to ICD-10
F84.2	Rett Syndrome
ICD-10 online (WHO version 2019)

The Rett Syndrome is a pervasive developmental disorder . The cause of this is an encephalopathy that follows an X-linked dominant inheritance. The X-linked mutations occur at the time of conception in both male and female embryos. In male embryos, however, the mutations  almost always lead to intrauterine fetal death due to hemizygosity . For this reason, girls with Rett syndrome ( gynecotropia ) are observed almost exclusively . The Rett syndrome was described for the first time in 1966 by the Viennese pediatrician Andreas Rett (1924–1997). In Germany the frequency is estimated at 1: 15,000 to 1: 10,000.

The affected children seem to develop properly at first. Between the seventh month and the second year of life, however, after a variable phase of developmental arrest, the child loses at least some of the skills already learned, in particular speaking and using the hand. The condition of the children then stabilizes again and reaching a normal age is possible. People with Rett syndrome typically show symptoms of autism and impaired movement coordination ( ataxia ). Some sick people have an intellectual disability , many speak a few words and can follow simple prompts. Also characteristic of Rett syndrome are epileptic seizures and hand stereotypes, which are similar to the movements when washing hands.

In the diagnosis code DSM-IV , the Rett syndrome, the Asperger syndrome and the “unspecified profound developmental disorder” are summarized under one number 299.80 . In the ICD-10 , Rett syndrome has its own digit F84.2 .

causes

In 1998 the cause of Rett syndrome was located at Baylor College of Medicine in Houston and at Stanford University . The cause is a mutation in the MECP2 gene . Since October 1999 it has been possible to diagnose Rett syndrome using a genetic test that can be used very early in the child's development.

It is approximately 80 to 90% of cases dominant de novo - mutations of the X chromosome (new mutation of the germ line), which are produced mainly in the male germ line and are therefore passed on mainly by the father to the daughter (the sons received from the father the Y chromosome ).

The MeCP2 gene (Methyl-CpG-Binding Protein 2) is located in the chromosomal region Xq28. MeCP2 is a transcription factor that selectively binds to methylated CpG islands and represses the transcription of various genes . This permanently disrupts the cholesterol metabolism .

Mutations in this gene are also involved in Lindsay burn syndrome .

An earlier onset, more severe course of the disease can also be triggered by a defect in the CDKL5 (cyclin-dependent kinase-like 5) gene , which is located in the Xp22 region. Epilepsy, which is difficult to treat, occurs in the first three months.

Symptoms and ailments

Rett discovered the typical hand movements (washing movements) in 1965, when two young girls were sitting on their mothers 'laps in the waiting room of his practice and they accidentally let go of their daughters' hands at the same time. These hand stereotypes are now considered the most typical criterion for Rett syndrome. Over time, additional auxiliary diagnostic criteria were added. The Austrian Rescue Syndrome Society (ÖRSG) presents the following most important criteria on its homepage.

The main criteria are:

• An initially normal development of the child is followed by a standstill and then a clear regression between the 6th and 18th month . Acquired skills are forgotten again, normal use of the hands is lost.
• Normal head circumference at birth. Slowing of skull growth between the 5th month and the 4th year of life.
• The language development occurs on delayed or remains at an early stage stuck. Often the language is completely absent.
• Stereotypes of hands : washing movements in the chest or in the level of the mouth . Rhythmic movements of the upper body.
• Severe cognitive disability , real intelligence is difficult to assess.
• Unsteady, wide-legged gait . Often times, the ability to walk unaided does not develop at all.
• Suspected diagnosis up to 2 to 5 years of age.

In addition, a number of auxiliary criteria for Rett syndrome are listed, which sometimes occur but are not absolutely necessary for diagnosis:

• Breathing irregularities
• EEG abnormalities with slowing down of background activity, epileptiform patterns and reduction in REM sleep (the dream phase )
• epileptic seizures (affects about 8 in 10 people)
• poor blood flow to the extremities
• Grinding teeth
• Scoliosis
• retarded growth
• increased muscle tone ( hypertension ) especially in older people with Rett syndrome
• sleep disorders

Disease stages

Hagberg and Witt-Engerström have created a general classification of the development of people with Rett syndrome, which is recognized worldwide and is divided into four stages. The information on the time and duration of the respective phase is given in extremely different sources in different sources and is therefore only a guideline.

• 1st stage: stage of stagnation (6th - 18th month of life)

At this stage, motor development slows down and it can come to a standstill. The progress previously made in development and the learning of new things come later and more slowly. Over time, the children's attention and activity decrease. The toddler is not interested in the toys presented, and eye contact is also less than with babies of the same age. The increase in head circumference lags behind the normal development. This phase can take a few months.

• 2nd stage: phase of regression (starts between the 1st and 3rd year of life)

A general regression of development is characteristic. Skills that have already been acquired (e.g. functional use of the hands, language) are lost in this phase. In addition, the typical hand movements (washing, wrestling and clapping movements) appear. The regression can start suddenly and dramatically or it can be delayed. The affected children are socially and emotionally withdrawn, isolated, have little contact with their environment and also fall into sudden screaming phases. From descriptions of the children by their parents, one assumes that at this stage the girls lose the ability to grasp situations as a whole, to relate stimuli to one another. In this context, Lindberg speaks of disorders of sensory perception and integration. "The signals from their own body and from the outside world seem to overwhelm and confuse them rather than conveying meaningful information." This disorder leads in part to the misdiagnosis of early childhood autism. The first cerebral seizures (abnormal EEG) also occur in this phase. The duration of the 2nd stage is described by several weeks and months.

• 3rd stage: plateau phase (2-10 years of age)

After the rapid regression phase, girls with Rett syndrome now go through a phase of relative calm. There is a reduction in autistic traits, their behavior improves due to less irritability and they cry less. They begin to be interested in their environment again, with phases of attention alternating with phases of “being withdrawn”. The ability to communicate improves. In addition, the already known symptoms such as teeth grinding, hand stereotypes and epileptic seizures remain. In addition, there is increased apraxia (neurological inability to carry out learned, purposeful movements or actions, despite the ability to perceive and move) and ataxia (neurological disturbance of the movement sequences, these are unusually jerky). (→ Development) Seizures occur frequently in this phase and hand stereotypes increase. Gross motor skills are largely retained and only slowly deteriorate. The less secure gait is also clearly evident.

• 4th stage: phase of motor deterioration (from about 10 years of age)

At this stage the contact behavior opens up even further. The frequency of seizures decreases, and people with Rett syndrome show cognitive progress. "The gross motor skills deteriorate noticeably and weakness, emaciation, scoliosis and spasticity force most girls into immobility and into a wheelchair."

Cognition and language

• The most intensive communication options are undoubtedly the look and facial expressions .
• According to assessments by parents and special education teachers, girls with Rett syndrome are to be classified as severely cognitively disabled. However, Dobslaff admits that it is very difficult to determine their exact level of cognitive development.
• Lindberg assumes that girls with Rett syndrome can classify different objects. The ability to order and classify is of particular importance for information acquisition, analysis and processing, sensory integration .
• Dobslaff comes to the view that the girls with Rett syndrome can only classify things that are familiar to them and things in known situations. For example, cups and plates are properly sorted.
• The girls also recognize personal property and differentiate between it and that of other children, but they are overwhelmed when they have to classify different types of toys.
• Girls with Rett syndrome have a problem transferring lessons learned to new conditions.
• The girls can hardly remember actions taken if they are demonstrated too quickly or repeated too seldom.
• Dobslaff takes the assumption that complex 'if-then-relationships' cannot be recorded, which can lead to lasting frustrations for the girls and women and possibly also explains their apparently frequent disinterest.
• Various authors can confirm the object permanence and a pronounced understanding of symbols. People with Rett syndrome know that an image is representative of an object and can mostly recognize things / facts in the original and in the image. They are also able to interpret and associate images with regard to their content.
• In most cases, the girls and women no longer have access to spoken language (expressive language). In contrast, their understanding of language (receptive language) is relatively complex.
• Depending on the stage of Rett syndrome and individual abilities, communicative behavior is difficult to recognize. It often appears that the girls are unable to establish contact and communicate, at least there is no doubt that there is a serious communication impairment. In addition, their motor impairments and their apraxias inhibit their communication skills.

Consequences and complications

Rett syndrome results in severe physical and mental disability for life. Children with Rett Syndrome need the help and support of others over and over again. The epileptic seizures can lead to falls and injuries. The motor difficulties, the unsteady gait, the increased muscle tension and the scoliosis lead to limitations in mobility and immobility. The poor language development makes communicating with the environment difficult. These (and other symptoms) make an independent and independent life impossible.

Differential diagnosis

Differential diagnostics include Kleefstra syndrome and Snyder-Robinson syndrome .

treatment

There is currently no therapy that cures Rett syndrome. Nevertheless, there are some supportive therapies that can favorably influence some areas or sub-areas of multiple disabilities. Not all of the therapies presented below are suitable for every child with this syndrome; Here, consideration of the family situation and professional advice play an essential role. However, it makes sense to combine individual therapies, but without over-treating the child.

• physical therapy

For many patients, this form of help will play a role throughout their lives. Here z. B. Assistance with crawling, walking, getting up in a standing position, sitting down and standing up or also to avoid fractures can be given. The top priority here is to maintain mobility. Various aids are required for this, depending on the child.

• Hippotherapy

About a quarter of the patients use this form as balance training. You can reduce your motor insecurity and improve your posture, coordination and balance. Furthermore, the stereotypical hand movements are reduced, since the patients have to use their hands in a meaningful way to maintain balance on horseback. The therapy relaxes the children and improves their alertness, it also gives them emotional satisfaction and joy in “being able to do something”.

• Occupational therapy

The aim is to reduce dependency in everyday life, improve independence when eating and dressing, and improve gross and fine motor functions.

• Other relevant therapies
  • Ketogenic Diet
  • Music therapy
  • Speech therapy
  • Hydrotherapy
  • Doman therapy
  • Supported communication
  • Peto
  • Speech therapy - important for problems with eating and drinking

literature

• Otto Dobslaff: Promotion of children with intellectual disabilities. Rett Syndrome. Marhold, Berlin 1999, ISBN 3-89166-555-5 .
• Angelika Koch: Not without language. Assisted communication for a girl with Rett Syndrome. 2nd revised and expanded edition. Göttert, Diepenau 2006, ISBN 3-936469-39-3 .
• Barbro Lindberg: Rett Syndrome. An overview of psychological and educational experiences. 3. Edition. WUV-Universitäts-Verlag, Vienna 2000, ISBN 3-85114-527-5 .
• Barbro Lindberg: Understanding Rett Syndrome. A Practical Guide for Parents, Teachers, and Therapists . 2nd revised edition. Hogrefe, Cambridge, MA et al. a. 2006, ISBN 0-88937-306-X .

Individual evidence

1. ↑ Christie M Buchovecky, Stephen D Turley, et al. a .: A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome. In: Nature Genetics. 45, 2013, pp. 1013-1020, doi: 10.1038 / ng.2714 .
2. ↑ MeCP2.  In: Online Mendelian Inheritance in Man . (English).
3. ↑ CDKL5.  In: Online Mendelian Inheritance in Man . (English).
4. ↑ Lindberg. Rett Syndrome. WUV University Press. Vienna 1994. 2nd edition.
5. ↑ Lindberg 1994, p. 20.
6. ↑ Lindberg 1994, p. 18.
7. ↑ Dobslaff 1999, p. 209.
8. ↑ Lindberg 2000, p. 50.
9. ↑ Dobslaff 1999, p. 239.
10. ↑ Lindberg 1990, p. 3.
11. ↑ Source of the paragraph: Archived copy ( Memento of the original from October 18, 2006 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. - As of January 24, 2006. 

Web links

• Rett Syndrome.  In: Online Mendelian Inheritance in Man . (English)

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !