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Rett Syndrome

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Rett Syndrome
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What Is Rett Syndrome?
Causes of Rett Syndrome
Symptoms of Rett Syndrome
Diagnostic Criteria for Rett Syndrome
Main Rett Diagnostic Criteria
Videos To Watch:
About Rett Syndrome
Rett Syndrome - The View - January 28-2011

Kate Foundation for Rett Syndrome Research

 

  • What Is Rett Syndrome (RS)?
    Rett syndrome is a genetic developmental disorder that almost always affects girls, but is rarely seen in boys.
    Rett Syndrome effects 1 in 15,000 little girls. It was identified by Dr. Andreas Rett, an Austrian doctor who first described it in an article in 1966. It was recognized as a disorder in 1983, when a second article was published. Children with Rett syndrome can display a wider range of disabilities that range from mild to severe. The progression and severity of the disorder depends on a variety of genetic mechanisms.

  • MECP2 Gene Mutation: Rett Syndrome is caused by mutations on the X chromosome on a gene called MECP2. Researchers identified the MECP2 gene in 1999. It is one of the genes responsible for making a protein needed for normal brain development. The MECP2 gene makes a protein that is necessary for the normal development of the nervous system, especially the brain. Rett syndrome affects areas of brain function that are responsible for cognitive, movement, sensory, emotional, motor and autonomic function. These, in turn, can have an impact on learning, speech, sensory sensations, mood, breathing, cardiac function, as well as chewing, swallowing and digestion. 

  • Rett syndrome affects areas of brain function that are responsible for cognitive, movement, sensory, emotional, motor and autonomic function. Thesehave an impact on learning, speech, sensory sensations, mood, breathing, cardiac function, as well as chewing, swallowing and digestion. 

  • Girls have two X chromosomes in each cell but one of the X chromosomes is inactivated and one remains active. Depending on the randomly determined balance of which X chromosome is inactivated (the one with OR without the MECP2 mutation) the severity of the girls condition may vary.

  • Two girls who are the same age and have the same mutation can have very different disabilities.

  • Boys only have one X chromosome, with the other being the Y chromosome.  In boys, if they have a full MECP2 mutation it is active in all cells resulting in early miscarriage or a severe clinical picture.

  • There are children who have signs and symptoms of Rett Syndrome who do not have this genetic mutation and others who have a different genetic mutation.

  • Rett syndrome is a genetic disorder but less than 5% of recorded cases are inherited or passed from one generation to the next.

Causes Of Rett Syndrome

  • Most cases of Rett syndrome are caused by a genetic mutation on the MECP2 gene, which is located on the X chromosome.
  • Some patients are noted to have variant forms of Rett syndrome because of unique features (e.g. congenital onset, infantile seizures).

  • Many of these “variant forms” are now know to be caused by mutations in other genes.

  • Chromosomes contain the genes that dictate how we look, grow and function. The X chromosome is one of two chromosomes that establish a person’s gender.

  • The progression and severity of the disorder depends on the type, location and severity of the genetic mutation and balance of “X-inactivation.”

Symptoms of Rett Syndrome

  • Most babies who have Rett syndrome appears to have typical development for the first months of life.

  • At 6 to 18 months, development slows and many children will lose previously learned skills.

  • The first symptom is often low muscle tone (hypotonia)

  • Then comes diminished eye contact.

  • Girls will develop problems with communication skills and develop intentional use of their hands.

  • They start to make repetitive hand movements often similar to washing motions.

  • The normal rate of head growth begins to slow.

  • Some girls develop seizures and/or irregular breathing patterns during the waking hours.

  • Over the long term, there is a decline in motor function including the inability to walk or move in some girls.

  • Boys with Rett syndrome have a variety of clinical presentations.

Diagnostic Criteria of Rett Syndrome - Diagnosis of Rett syndrome is based upon clinical criteria that were revised in 2010.

How Rett syndrome manifests itself and progresses varies from child to child.

  • Slow Head Growth: Rett syndrome should be considered when slowing of head growth is observed after birth.
  • Blood Tests: These tests are able to confirm the syndrome in up to 80 percent of all cases. Blood tests will to identify the mutation of the MECP2 gene. Since the MECP2 mutation can also be found with other disorders, this finding alone is not enough to make a conclusive diagnosis of Rett syndrome.
    Some children with Rett syndrome do not have the MECP2 mutation and may be diagnosed with classical or variant Rett syndrome based upon meeting the specific diagnostic criteria above and testing for other genetic changes may be recommended in some. Variant forms of Rett often have more preserved speech and/or motor abilities. There are also variant forms with congenital onset, infantile seizures and with late onset of regression at preschool or school age.

  • Molecular Testing: A formal iagnosis requires either a molecular diagnosis of the mutation (a DNA test)

  • Signs and Symptoms: Observable signs and symptoms need to be present for a diagnosis.

There are specific diagnostic criteria for typical/classical and for atypical/variant Rett syndrome:

  • Both forms require that the child have had a period of regression in developmental skills followed by stabilization and/or improvements.

  • A case of classical Rett Syndrome will have all of the main criteria while those with atypical Rett Syndrome may only have some.

  • If the diagnosis of Rett syndrome is suspected, a blood test looking for the mutation on the X chromosome of the gene called MECP2 should be obtained.
  • Children who do not have the MECP2 mutation may be diagnosed with classical or variant Rett syndrome, based upon meeting the specific diagnostic criteria  and testing for other genetic changes.
  • Variant forms of Rett Syndrome often have more preserved speech and/or motor abilities.
  • There are also variant forms with congenital onset, infantile seizures and with late onset of regression at preschool or school age.

The following exclude a diagnosis of classical Rett but may be present in atypical Rett syndrome:

  • Brain injury due to trauma
  • Neurometabolic disease
  • Severe infection causing neurologic problems or grossly abnormal development in the first 6 months of life.  

Main Rett Diagnostic Criteria

For diagnosis of atypical Rett syndrome, at least 5 supportive criteria (listed below) must also be present.  

  • Partial or complete loss of acquired purposeful hand skills
  • Partial or complete loss of acquired spoken language
  • Gait abnormalities
  • Stereotypic hand movements such as wringing, squeezing, clapping, tapping, mouthing or hand-washing movements

Supportive Criteria for Rett Syndrome

  • Breathing disturbances when awake
  • Tooth grinding when awake
  • Impaired sleep
  • Abnormal muscle tone
  • Peripheral vasomotor (nerves and muscles that cause blood vessels to constrict or dilate) disturbances
  • Growth retardation
  • Small and cold hands and feet
  • Inappropriate laughing or screaming spells
  • Diminished sensitivity to pain
  • Intense eye communication and eye-pointing behavior

About Rett Syndrome
(6:37 minutes)

 

Rett Syndrome - The View - January 28-2011
(9:34 minutes)

 

Kate Foundation for Rett Syndrome Research Gala Video
(7:29 minutes)

https://www.youtube.com/watch?v=G9h1d2c9T5o

 




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