What is Rett syndrome?
Rett syndrome is a childhood neurodevelopmental disorder characterized by normal early development followed by loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, gait abnormalities, seizures, and mental retardation. It affects females almost exclusively.
The disorder was identified by Dr. Andreas Rett, an Austrian physician who first described it in a journal article in 1966. It was not until after a second article about the disorder was published in 1983 that the disorder was generally recognized.
The course of Rett syndrome, including the age of onset and the severity of symptoms, varies from child to child. Before the symptoms begin, however, the child appears to grow and develop normally. Then, gradually, mental and physical symptoms appear. Hypotonia (loss of muscle tone) is usually the first symptom. As the syndrome progresses, the child loses purposeful use of her hands and the ability to speak. Other early symptoms may include problems crawling or walking and diminished eye contact. The loss of functional use of the hands is followed by compulsive hand movements such as wringing and washing. The onset of this period of regression is sometimes sudden.
Another symptom, apraxia — the inability to perform motor functions — is perhaps the most severely disabling feature of Rett syndrome, interfering with every body movement, including eye gaze and speech.
Individuals with Rett syndrome often exhibit autistic-like behaviors in the early stages. Other symptoms may include toe walking; sleep problems; wide-based gait; teeth grinding and difficulty chewing; slowed growth; seizures; cognitive disabilities; and breathing difficulties while awake such as hyperventilation, apnea (breath holding), and air swallowing.
What causes Rett syndrome?
Rett syndrome is caused by mutations (structural alterations or defects) in the MECP2 (pronounced meck-pea-two) gene, which is found on the X chromosome (click the "Who It Affects" tab for a discussion of the importance of the involvement of the X chromosome). Scientists identified the gene — which is believed to control the functions of several other genes — in 1999. The MECP2 gene contains instructions for the synthesis of a protein called methyl cytosine binding protein 2 (MeCP2), which acts as one of the many biochemical switches that tell other genes when to turn off and stop producing their own unique proteins. Because the MECP2 gene does not function properly in those with Rett syndrome, insufficient amounts or structurally abnormal forms of the protein are formed. The absence or malfunction of the protein is thought to cause other genes to be abnormally expressed, but this hypothesis has not yet been confirmed.
Who gets Rett syndrome?
Rett syndrome affects one in every 10,000 to 15,000 live female births. It occurs in all racial and ethnic groups worldwide. Prenatal testing is available for families with an affected daughter who has an identified MECP2 mutation. Since the disorder occurs spontaneously in most affected individuals, however, the risk of a family having a second child with the disorder is less than 1 percent.
Rett Syndrome is Reversible!
The Scientific Details
Restoration of fully functional MECP2 over a four week period eradicated tremors and normalized breathing, mobility and gait in mice that had previously been fully symptomatic and, in some cases, only days away from death.
Adrian Bird, Ph.D of the University of Edinburgh stated
Like many other people, we expected that giving MECP2 to mice that were already sick would not work. The idea that you could put back an essential component after the damage to the brain is done and recover an apparently normal mouse seemed farfetched, as nerve cells that developed in the absence of a key component were assumed to be irrevocably damaged. The results are gratifyingly clear, though, and must give hope to those who are affected by this distressing disorder.
Bird is Buchanan Professor of Genetics at University of Edinburgh and Director of the Wellcome Trust Centre for Cell Biology. MECP2, first identified by Bird in 1990, is considered to be a protein that regulates the expression of other genes by turning them off at the appropriate time.
In 1999 Huda Zoghbi, M.D., Professor, Departments of Molecular and Human Genetics, Pediatrics, Neurology, and Neuroscience at Baylor College of Medicine discovered that RTT is caused by mutations in the MECP2 gene. Mutations in MECP2 are now being seen in some cases of childhood schizophrenia, classic autism and learning disabilities.
The findings are extraordinary, and are of relevance not only to Rett Syndrome but to a much broader class of disorders, including autism and schizophrenia. The successful restoration of normal function demonstrated in the mouse models suggests that if we can develop therapies to address the loss of MECP2 we may be able to reverse neurological damage in children and adults with Rett, autism and related neuropsychiatric disorders,
commented Zoghbi.
As well as losing overt behavioral defects, the mice also recovered a key electrophysiological function of the brain. This was determined by measuring LTP (long-term potentiation) which provides a quantifiable measurement of the ability of neurons to respond to stimulation. LTP has long been thought to reflect the cellular basis of learning and memory. Though LTP in RTT mice models was defective, it was restored to normal function by the reversal experiments.
The reversal of neurological defects, reported in the remarkable article by Guy et al, is surprising because the cause of the symptoms occurred early in development and was expected to be permanent. Of particular note is the recovery of LTP, which is the best current physiological correlate of learning and memory. These findings are very encouraging for those searching for a treatment because they give hope that the symptoms could not only be halted from progressing, but the course of the disease itself may be able to be reversed,
stated Fred Gage, Ph.D. of the Salk Institute of Biological Studies.
"Dr. Bird's astonishing results usher in a new era for Rett Syndrome and other autism spectrum disorders. The reversal experiments provide justification for aggressive exploration of next steps on all fronts, from drug discovery to gene correction " commented Monica Coenraads, co-founder and Director of Rett Syndrome Research Trust and mother of a young daughter with the disorder.
Intrigued? Read more at Reuters.
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5. Laboratory Mice Cured of Rett Syndrome
Researchers affiliated with the Wellcome Trust have shown evidence that Rett syndrome, a neurodevelopmental disorder that afflicts one in every 10,000 female births, might be curable. Caused by a mutation, the disorder prevents children from walking, talking or developing normally and gives them terrible tremors. By creating mice with a similar affliction, Adrian Bird and his colleagues at Edinburgh University and the University of Glasgow tested the effects of fixing the bad gene. In the Feb. 23 issue of Science, they explained that the disease does not cause permanent damage to nerve cells, and breathing problems and tremors in mice stop when they are nudged into producing normal MeCP2 -- the protein corrupted by the disease.
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