Lynchburg, VA
Inclusion and co-teaching are becoming predominant in school systems across the country. Educators, both special education and general education teachers, are being introduced to children with disabilities that are caused by rare disorders. Requirements for these children to be placed in the least restrictive environment mandates that educators become knowledgeable of these disorders. One such disorder, which educators may not be familiar with, is Rett syndrome.
In 1966, Dr. Andreas Rett, an Austrian physician, published a report describing this disorder (Lee, 1999). According to a review of history by the International Rett Syndrome Association (IRSA, n.d.), Dr. Rett had become intrigued several years earlier when he had noticed two girls in his office with similar symptoms. After further inquiry, he discovered that there were six other girls in his practice that had the same characteristics. His assumption was that these girls shared the same disorder. He continued his research by filming the girls and traveling around Europe to see if he could locate others with the same symptoms. Around the same time, Dr. Bengt Hagberg, a Swedish physician, had discovered patients of his own who had these symptoms. He collected data and his plan was to study these data at a time in the future (IRSA, n.d.).
When the report from Dr. Rett was published it appeared mostly in German medical journals so the research about the disorder did not become well-known fact. In 1983, however, Dr. Hagberg published his own report and it was in a mainstream journal. It was at that time that Rett syndrome became a recognized disorder and the name it was given gave credit to the original physician to discover the disorder (IRSA, n.d.).
ARett syndrome, which affects 1 in 10,000-15,000 girls, is an X-linked progressive neurodevelopmental disorder. Affected girls usually develop normally until 6-18 months of age@ (Baker, 1999, p.7). The purpose of this paper is to explore the causes, characteristics, and interventions associated with Rett syndrome.
Causes
Although this disorder was identified as early as 1966, it was not until 1999 that the gene involved was discovered. A team, under the direction of Dr. Huda Zoghbi, discovered a mutation on the methyl CpG-binding protein 2 (MeCP2) gene found on the Xq28 chromosome (Baker, 1999). Locating the gene on the X chromosome gave the proof needed to show that the disorder was a X-linked disorder and also, because only one X chromosome needs the mutation for the disorder to occur, it is a dominant disorder. This scenario explains why the disorder is mostly diagnosed in girls. Irby (2000) explains that the MeCP2 mutation is usually fatal to boys. One exception to this rule is the diagnosis of Klinefelter syndrome. In this disorder the boys have an extra X chromosome making them XXY rather than XY. Rett Syndrome can occur if one of the X chromosomes has the MeCP2 mutation.
According to Baker (1999), the purpose of the MeCP2 gene is to silence transcription of other genes. A number of genes that affect normal development can be overexpressed when there is a loss of functioning in MeCP2. The International Rett Syndrome Association (n.d.) offers a good analogy to understanding the process. The organization states the syndrome [leaves]:
....those genes to act like overzealous electricians ignoring the wiring
plans for a new house. Instead of installing a network of carefully placed wires
and switches, these neuronal electricians create a hodgepodge of wires that cause
short-circuits and blown fuses (p. 4).
This analogy gives a simplified answer to a very complex problem.
The International Rett Syndrome Association (n.d.) states that scientists have determined that MeCP2 is active throughout the body, but is abundant in the brain. When there is a mutation in MeCP2 and Rett syndrome occurs, specific areas of the brain are affected. These areas are the frontal, motor, temporal cortex, brainstem, basal forebrain, and basal ganglia. All of these areas are critical to controlling basic functions. They are also critical to higher brain center, the cortex, during development in late infancy.
Research continues in the area of Rett syndrome. Mouse models are proving to be beneficial in the research of the progression of the disorder. Scientists are hopeful that they can discover ways to cure or slow down this disorder. They are focusing on the prenatal and early infancy stage, prior to six months, as their Awindow of opportunity@ (IRSA, n.d.).
Characteristics
As mentioned earlier, females diagnosed with Rett syndrome appear to develop in typical fashion until around the age of six to eighteen months. There also appears to have been normal prenatal and perinatal development (Graziano, 2004). Hypotonia (i.e., loss of muscle tone) appears to be the first symptom. Apraxia, which is the inability to perform motor functions, is the most disabling symptom. The most stereotypical behavior of females diagnosed with Rett syndrome is that of hand-wringing or washing and repetitive hand-to-mouth movements. According to Irby (2000), other symptoms include toe walking, sleep problems, difficulty chewing, and breathing problems. Fear also seems to be associated with Rett syndrome. When these girls are upset, they have a shakiness in their body.
Understanding the progression of Rett syndrome is made easier by reviewing the four stages that these females go through. These four stages give a guideline for the disorder. Characteristics of the first stage begin at approximately 6 to 18 months of age. The National Institute of Neurological Disorders and Stroke (NINDS, n.d.) refers to this as the early onset stage. According to Van Acker (1991), it is sometimes hidden due to the speed of development in infancy. Some of the symptoms are decreased head growth, floppy muscle tone, and decreased interest in play and environment. Gross motor skills may also be affected and delays in sitting and crawling may be observed.
Stage two is referred to as the rapid destructive stage and occurs between the age of 12 and 36 months (NINDS, n.d.). This is a period of regression for the child. According to Harris, Glassberg, and Ricca (1996), language, social, and motor skills deteriorate quickly. The stereotypical behavior of hand wringing and washing will begin during this stage. Periods of sleep apnea and hyperventilation will also begin to occur. This stage is also when social aloofness begins and females will begin to demonstrate what are thought to be autistic traits. This is the stage when they are often misdiagnosed with having autism. Seizure activity begins at this time and it is seen in one-fourth of the females. Parents report that their children are more irritable and that tantrums are common during this regression period. This stage may last for weeks or months (Van Acker, 1991).
Between the ages of two and ten stage three begins, the plateau or pseudo-stationary stage (NINDS, n.d.). As the name implies, this stage can last for years and will be the stage that most females are in for the majority of their lives. The autistic features of Rett syndrome seem to fade but motor functioning becomes more of a problem. Seizure activity is prominent during this stage. The females do appear to have more of an interest in their environment and attention span and alertness may improve.
Stage four, the motor deterioration stage, can last for years or decades (NINDS, n.d.). As one would assume by the title, this stage features muscle weakness, stiffness, spasticity, posturing difficulties, and scoliosis. Many times this stage requires the use of a wheelchair if there has not been one prior.
Rett syndrome is a very challenging disorder as can be seen by reviewing the various stages. There are many areas of concern. These stages not only give a general idea of what may occur during a given period in the child=s life, but it makes one aware of what lies ahead. Being knowledgeable about the progression of the disease will allow time for preparation to meet the needs of the child when these various problems occur.
Interventions
Rett syndrome presents many complications for the children diagnosed with it, yet they very often live into adulthood. The severity of the disorder may vary among individuals, but most interventions can be utilized across the Rett syndrome population. Areas for which interventions can be important are self-injurious behavior, nutrition, seizures, communication, and various areas for physical and occupational therapy.
Self-injurious Behavior
Self-injurious behavior has been identified in children with Rett syndrome. This usually occurs due to the rapid hand-to-mouth movement that is a stereotypical characteristic. According to Van Acker (1991), there have also been reported cases of self-biting, self-pinching, and self-hitting. According to Oliver (1999), all of these behaviors serve as sensory stimulation to these children.
Various interventions have been implemented to deal with self-injurious behavior and the rapid hand-to-mouth movements. These interventions have included elbow orthosis (i.e., splint) to decrease the hand to mouth movement and interventions such as differential reinforcement, response interruption techniques, and mitts to reduce self-injurious behavior. Use of the elbow orthosis did increase toy contact in one study but the orthosis can also present a discomfort to the child (IRSA, n.d.). Katisyannis, Ellenburg, Acton, and Torrey (2001) reported on a study which showed that the most successful intervention for self-injurious behavior was differential reinforcement paired with response interruption. The benefit to decreasing these behaviors is that the child becomes more alert and focused when hand movements and self-injurious behaviors are controlled.
Nutrition
Girls with Rett syndrome have difficulty maintaining adequate weight. One of the first symptoms noticed by Rett was a wasting affect and growth retardation (Lee, 1999). Therefore, nutrition is a very important area of intervention.
The loss of purposeful hand use makes it difficult to teach self-feeding techniques. Some adaptations to feeding utensils have proven effective, but maintaining weight can present difficulties. According to Lee (1999), Kathleen J. Motil, pediatrician and nutritionist, has had success with fitting patients with a gastrostomy button. This surgically implanted device allows nutrients to be administered while the child is sleeping. Use of the button has proven successful in increasing the weight and reversing the downward trend of poor growth. Also of importance is consulting with a nutritionist to develop a weight management plan.
Seizures
Seizures are very common in girls with Rett syndrome. This is not a surprising fact because the syndrome affects the nervous system, however, the cause of seizures in this disorder is unknown. According to Van Acker (1991), there are numerous EEG abnormalities for these girls between the ages of three and ten.
Information retrieved from The International Rett Syndrome Association (n.d.) states that determining whether a seizure is occurring in a girl with Rett syndrome may be difficult. What may appear to be a seizure could actually be uncontrollable movements that are characteristic of the disorder. If it is determined the child is having seizures there are medications, such as Tegretol, available to treat them. However, it has been found that many children are sensitive to the medications and may overreact (IRSA, n.d.).
Communication
Lack of communication abilities in a child diagnosed with Rett syndrome create a major obstacle in their education. According to Woodyatt and Ozanne (1992), communication skills are severely impaired and most girls are at a preintentional level of communication (i.e., caregiver will assign a meaning). An important aspect is to determine if the child is attempting to communicate using verbal or nonverbal behaviors.
Augmentative and Alternative Communication (AAC) can be very beneficial when dealing with children who have Rett syndrome. Some examples of AAC are eye gaze and voice output devices. Using these can lead to formal and effective communication (Van Acker, 1991).
According to Gaines (2005), eye gaze may be difficult for some girls, but spacing items far apart may help. By placing Velcro on a frame, pictures or objects can be attached and the child can choose based on Agazing@ at the object. Eye gaze vests are also available. Pictures can be placed in pockets on a vest that can be worn by an adult. The advantage of the vest is that it is portable and can be used in different settings.
Gaines (2005) also reports that voice output devices range from low to high tech. The
low tech systems use digitized speech and only use a limited amount of vocabulary. The high tech systems are much more advanced and can allow for more vocabulary, they are also more expensive. The low tech systems can be activated by a single switch. Van Acker (1991) points out that there have been successes by implementing single switches to activate toys and computers. The low tech devices are inexpensive, which make them accessible to the school systems. The advantage to the voice output devices is that the child=s response can be heard by everyone. Shotko, Koppenhaver, and Erickson(2004) recommend that further studies be conducted to explore the possibilities of initiating communication, enhancing communication, and contextualizing it over multiple environments.
Physical Therapy
Physical therapists are a very important resource for children with Rett syndrome. Although they cannot alter the course of the disorder, they are successful in maintaining and improving function (Katisyannis et al, 2001). One aspect they must keep in mind is that they can only treat the symptoms and they must individualize each intervention for the specific child they are working with (Van Acker, 1991).
According to The International Rett Syndrome Association (n.d.), physical therapy should be one of the first sought after interventions. Physical therapy plays an important role in each stage of the syndrome. During stage one, they should focus on independent sitting, standing, and
walking. Stage two requires the therapist to focus on range of motion and ambulation. Scoliosis
may be more prominent in stage three and focus should be placed on seating, to assist with positioning, and transporting. Stage four requires that all aspects from the previous stages be incorporated (IRSA, n.d.). The role of the physical therapist is crucial to the well being of a child with Rett syndrome throughout their lives.
Occupational Therapy
Occupational therapists also play a crucial role. Their main focus is on hand use and eating skills. Although feeding skills may be difficult to teach, they can assist the child with adaptive eating utensils and work toward a possible goal of independent feeding (IRSA, n.d.).
Occupational therapy can also work with the child on sensory processing issues. Sensory information is not well organized for girls with Rett syndrome. Integrative therapy, such as tactile activities and joint compression, can help the child better organize information and be better able to respond. The occupational therapist is also an excellent source to assist with accommodations and adaptive equipment in the classroom (IRSA, n.d.).
Discussion
Educators should be aware that, with the emphasis of least restrictive environment, public schools will be addressing the needs of children with Rett syndrome (Katsiyannis et al, 2001). It would be beneficial to educators to be aware of certain aspects when working with a child diagnosed with Rett syndrome. The International Rett Syndrome Association offers helpful hints for the educators who have children with the syndrome in their classroom (see Appendix A).
As with most children with disabilities, early intervention is vital (Harris et al, 1996). Personnel should be aware of behavioral interventions, focus on individualized approaches, and employ least intrusive interventions (Katsiyannis et al, 2001). Due to the fact that physical and occupation therapies are crucial for these children school personnel should also have the educational technology for reaching these children (Harris et al, 1996). Educators should be aware that effective collaboration will be very important for the success of a child with Rett syndrome in the classroom. The most important point for educators to remember is offered by Shotko et al (2004), Astudents with Rett Syndrome, as well as other disabilities, can and should be educated with the expectation that they can learn@ (p. 155).
Appendix A: Education Helpful Hints (IRSA, n.d.)
Education Helpful Hints
• Assume that she understands you.
• She may need a security symbol, such as a blanket or doll.
• Show consideration for her fears and hesitancies.
• Limit outside stimuli to those that are necessary.
• Explain everything to her before you do it (especially if you are moving her).
• Make situations meaningful.
• Choose activities that appeal to her emotions and her senses.
• Make sure activities are age-appropriate.
• Structure activities in a fixed sequence.
• Give her one task at a time.
• Schedule her activities with tangible reminders (bag by the door).
• Choose signals that she understands (words, signs, pictures).
• Combine several signals so that she gets more than one cue.
• Don’t say it, sing it.
• Allow her to move about her environment; she learns from taking it in.
Source: International Rett Syndrome Association.
Thursday, January 28, 2010
Sensory-Motor Rehabilitation in Rett Syndrome
By Maria Rosa Pizzamiglio
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Role of Occupational Therapy in Rett Syndrome
Prepared by Maryke Lawton and Brenda Gutierrez
Occupational Therapists, Children’s Hospital at Westmead
a) Occupational Therapy and Rett Syndrome in the literature
Articles of interest to Occupational therapists working with Rett Syndrome can be divided into two broad categories:
• Articles including information on therapy in general for Rett Syndrome. Eg:
o Cass H, Reilly S, Owen L, Wisbeach A, Weekes L, Slonims V, Wigram T, Charman T (2003). Findings from a multidisciplinary clinical case series of females with Rett syndrome. Journal of Developmental Medicine and Child Neurology (45); 325 – 337.
o Van Ackler R (1991). Rett Syndrome: A review of current knowledge. Journal of Autism and Developmental Disorders (21); 4: 381 – 406
o The Rett Syndrome Handbook: In Words You Can Understand from Those Who Understand. Hunter, K (1999). International Rett Syndrome Association.
• Articles on approaches to hand function, including management of hand stereotypies. Eg:
o Berryman D and Barrett L. (2002). Hand management in Rett Syndrome. Rett Syndrome Association of Australia (RSAA) Newsletter July 2002.
o Kubas E (1992). Use of splints to develop hand skills in a woman with Rett Syndrome. The American Journal of Occupational Therapy 46(4); 364 – 368.
o Naganuma G and Billingsley F (1988). Effect of hand splints on stereotypic hand behaviours of three girls with Rett Syndrome. Physical Therapy 68 (5), 664-671
o Tuten H and Miednaer J (1989). Effect of hand splints on stereotypic behaviour of girls with Rett Syndrome: A replication study. Physical Therapy 69 (12), 1099 – 1103.
o Woodyatt, G., & Sigafoos, J. (2000). Effects of amount and type of social interaction/activity on stereotyped hand mannerisms in individuals with Rett syndrome. Australasian Journal of Special Education, 23, 15-24.
b) Occupational Therapy and Rett Syndrome in the Rett Syndrome Multidisciplinary Management Clinic (CHW)
• Consultative approach
• Focus is on review and input regarding:
o Generic Occupational Therapy issues
o Rett Syndrome specific issues
• Frequently provided information listed
• Common interventions listed
• Support to community therapists
c) Occupational Therapy and Rett Syndrome in the Community
• Liaison and support to community therapists
• Provision of information to community therapists
• Provision of information to community groups
• Presentations at meetings, inservices and conferences when needed
Therapy ideas:
General principles
• Look for potential – for example use of eye gaze, or initiation of movement towards a desired object
• Keep in mind the affect of dyspraxia. Often times there is a marked delay between a prompt and reaction. Video-recording a session may help identify patterns
• Progress is often very slow. Rett Syndrome is not a neurodegenerative disorder, and improvements in functional self care and hand skills can be achieved throughout the lifespan (Cass et al, 2003)
Examples of goals (from Rett Syndrome Handbook):
• Identify and encourage use of head, elbows, or other body parts over which she may have better control
• Maximise hand use for functional activities
• Develop ability to access communication devices
• Develop ability to access a variety of assistive technology
• Improve ability to assist with dressing
• Improve ability to perform independent feeding skills
• Improve ability to assist with grooming activities
• Improve ability to tolerate sensory input in school setting
Hints: (from Rett Syndrome Handbook)
• Focus on enjoyable hand activities during the regression phase (rather than on fine-motor skills)
• Provide physical assistance
Orthoses and assistive devices to consider: (from Rett Syndrome Handbook)
• Splints can position thumb for grasp
• Adapt materials to make easier to grasp
• Consider cuffs and loops to assist with grasp, cut-out cups
• Switches for independence and leisure / pleasure
Other therapy ideas: (Based on Van Ackler (1991))
• Ideas to encourage functional hand use:
o Sensory input for hands (eg massage, exposure to a variety of textures)
• For apraxia and ataxia
o Weighted vests can be calming and decrease ataxia in some girls
o Use of a therapy ball
o Rotation and weight-shift activities
o Vestibular movement activities (if tolerated)
• Spasticity
o Positioning for safety (eg during mealtimes) and tone reduction
o Tone reduction activities such as rotation, weight-shift, vibration can temporarily reduce spasticity
• Scoliosis
o Positioning to ensure a symmetrical and erect posture in sitting (as far as possible)
Occupational Therapists, Children’s Hospital at Westmead
a) Occupational Therapy and Rett Syndrome in the literature
Articles of interest to Occupational therapists working with Rett Syndrome can be divided into two broad categories:
• Articles including information on therapy in general for Rett Syndrome. Eg:
o Cass H, Reilly S, Owen L, Wisbeach A, Weekes L, Slonims V, Wigram T, Charman T (2003). Findings from a multidisciplinary clinical case series of females with Rett syndrome. Journal of Developmental Medicine and Child Neurology (45); 325 – 337.
o Van Ackler R (1991). Rett Syndrome: A review of current knowledge. Journal of Autism and Developmental Disorders (21); 4: 381 – 406
o The Rett Syndrome Handbook: In Words You Can Understand from Those Who Understand. Hunter, K (1999). International Rett Syndrome Association.
• Articles on approaches to hand function, including management of hand stereotypies. Eg:
o Berryman D and Barrett L. (2002). Hand management in Rett Syndrome. Rett Syndrome Association of Australia (RSAA) Newsletter July 2002.
o Kubas E (1992). Use of splints to develop hand skills in a woman with Rett Syndrome. The American Journal of Occupational Therapy 46(4); 364 – 368.
o Naganuma G and Billingsley F (1988). Effect of hand splints on stereotypic hand behaviours of three girls with Rett Syndrome. Physical Therapy 68 (5), 664-671
o Tuten H and Miednaer J (1989). Effect of hand splints on stereotypic behaviour of girls with Rett Syndrome: A replication study. Physical Therapy 69 (12), 1099 – 1103.
o Woodyatt, G., & Sigafoos, J. (2000). Effects of amount and type of social interaction/activity on stereotyped hand mannerisms in individuals with Rett syndrome. Australasian Journal of Special Education, 23, 15-24.
b) Occupational Therapy and Rett Syndrome in the Rett Syndrome Multidisciplinary Management Clinic (CHW)
• Consultative approach
• Focus is on review and input regarding:
o Generic Occupational Therapy issues
o Rett Syndrome specific issues
• Frequently provided information listed
• Common interventions listed
• Support to community therapists
c) Occupational Therapy and Rett Syndrome in the Community
• Liaison and support to community therapists
• Provision of information to community therapists
• Provision of information to community groups
• Presentations at meetings, inservices and conferences when needed
Therapy ideas:
General principles
• Look for potential – for example use of eye gaze, or initiation of movement towards a desired object
• Keep in mind the affect of dyspraxia. Often times there is a marked delay between a prompt and reaction. Video-recording a session may help identify patterns
• Progress is often very slow. Rett Syndrome is not a neurodegenerative disorder, and improvements in functional self care and hand skills can be achieved throughout the lifespan (Cass et al, 2003)
Examples of goals (from Rett Syndrome Handbook):
• Identify and encourage use of head, elbows, or other body parts over which she may have better control
• Maximise hand use for functional activities
• Develop ability to access communication devices
• Develop ability to access a variety of assistive technology
• Improve ability to assist with dressing
• Improve ability to perform independent feeding skills
• Improve ability to assist with grooming activities
• Improve ability to tolerate sensory input in school setting
Hints: (from Rett Syndrome Handbook)
• Focus on enjoyable hand activities during the regression phase (rather than on fine-motor skills)
• Provide physical assistance
Orthoses and assistive devices to consider: (from Rett Syndrome Handbook)
• Splints can position thumb for grasp
• Adapt materials to make easier to grasp
• Consider cuffs and loops to assist with grasp, cut-out cups
• Switches for independence and leisure / pleasure
Other therapy ideas: (Based on Van Ackler (1991))
• Ideas to encourage functional hand use:
o Sensory input for hands (eg massage, exposure to a variety of textures)
• For apraxia and ataxia
o Weighted vests can be calming and decrease ataxia in some girls
o Use of a therapy ball
o Rotation and weight-shift activities
o Vestibular movement activities (if tolerated)
• Spasticity
o Positioning for safety (eg during mealtimes) and tone reduction
o Tone reduction activities such as rotation, weight-shift, vibration can temporarily reduce spasticity
• Scoliosis
o Positioning to ensure a symmetrical and erect posture in sitting (as far as possible)
Rett Syndrome: Dual Intervention - Music and Physical Therapy
Author: Cochavit Elefant & Meir Lotan
NORDIC JOURNAL OF MUSIC THERAPY
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NORDIC JOURNAL OF MUSIC THERAPY
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Hydrotherapy for Rett syndrome
By
Gonca Bumin
J Rehabil Med 2003; 35: 44–45
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Gonca Bumin
J Rehabil Med 2003; 35: 44–45
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Wednesday, January 27, 2010
Variants in synaptic protein linked to autism
Scientists have identified several autism-specific variants in a gene that lies within a chromosomal region linked to the disorder, according to a poster presented at the World Congress of Psychiatric Genetics in San Diego.
Interestingly, a closer look at one family tree suggests that some of these variants may be harmless when carried alone but, when inherited together, may lead to autism. The results are in press at the journal Autism Research.
Last year, Susan Christian and colleagues at the University of Chicago found a large, inherited DNA duplication in chromosomal region 15q13.1 shared by two brothers with autism1. The region — which has also been linked to schizophrenia, mental retardation and epilepsy — includes a gene called APBA2 that encodes a protein at the synapse, the nexus of neuronal communication.
A few months earlier, a different research group had found the same duplication in an individual with schizophrenia. That study also identified another individual with schizophrenia who is missing a segment on chromosome 2, disrupting neurexin 1, a synaptic protein that interacts with APBA22.
Because the APBA2 and NRXN1 proteins interact at the synapse, these variants are particularly good candidates for understanding what causes autism, says Ravinesh Kumar, Christian's collaborator and a postdoctoral fellow in William Dobyns' lab at the University of Chicago.
Several studies have linked NRXN1 and closely related genes to autism, prompting the researchers to investigate whether APBA2 mutations also crop up in people with the disorder. Mouse studies have shown that animals lacking the gene display abnormal social behaviors3.
"It might be that having the duplication, too much of the gene, might contribute to autism in some regard. But a mutation that disrupts the function of a gene might have a completely different effect," Kumar says. "It's really tricky to try to interpret."
Kumar sequenced the protein-coding regions of APBA2 in people with autism and in healthy controls. He drew the autism samples from the Autism Genetic Resource Exchange, a large gene bank of children with autism and their families.
Analyzing 512 blood samples from people with autism and 463 healthy controls, Kumar found seven novel rare APBA2 variants that are unique to the autism group, and four APBA2 variants specific to the control group. The difference is not great enough to say with statistical confidence that the variants are more common in autism.
One family in the autism group has a particularly interesting family tree, however. Two brothers, both diagnosed with autism, each carry the same two APBA2 variants. Their mother carries one of the variants, and their father the other, but neither parent has autism.
"Our hypothesis is that one event is not sufficient to give rise to autism, but having both is sufficient," Kumar says. "But at this point, it's still speculative."
Taken together with older studies, the results suggest that APBA2 is a good candidate gene for autism, he says, and deserves further study.
References:
Christian S.L. et al. Biol. Psychiatry 63, 1111-1117 (2008) PubMed
Kirov G. et al. Hum. Mol. Genet. 17, 458-465 (2008) PubMed
Sano Y. et al. J. Neurosci. 29, 5884-5896 (2009) PubMed
Interestingly, a closer look at one family tree suggests that some of these variants may be harmless when carried alone but, when inherited together, may lead to autism. The results are in press at the journal Autism Research.
Last year, Susan Christian and colleagues at the University of Chicago found a large, inherited DNA duplication in chromosomal region 15q13.1 shared by two brothers with autism1. The region — which has also been linked to schizophrenia, mental retardation and epilepsy — includes a gene called APBA2 that encodes a protein at the synapse, the nexus of neuronal communication.
A few months earlier, a different research group had found the same duplication in an individual with schizophrenia. That study also identified another individual with schizophrenia who is missing a segment on chromosome 2, disrupting neurexin 1, a synaptic protein that interacts with APBA22.
Because the APBA2 and NRXN1 proteins interact at the synapse, these variants are particularly good candidates for understanding what causes autism, says Ravinesh Kumar, Christian's collaborator and a postdoctoral fellow in William Dobyns' lab at the University of Chicago.
Several studies have linked NRXN1 and closely related genes to autism, prompting the researchers to investigate whether APBA2 mutations also crop up in people with the disorder. Mouse studies have shown that animals lacking the gene display abnormal social behaviors3.
"It might be that having the duplication, too much of the gene, might contribute to autism in some regard. But a mutation that disrupts the function of a gene might have a completely different effect," Kumar says. "It's really tricky to try to interpret."
Kumar sequenced the protein-coding regions of APBA2 in people with autism and in healthy controls. He drew the autism samples from the Autism Genetic Resource Exchange, a large gene bank of children with autism and their families.
Analyzing 512 blood samples from people with autism and 463 healthy controls, Kumar found seven novel rare APBA2 variants that are unique to the autism group, and four APBA2 variants specific to the control group. The difference is not great enough to say with statistical confidence that the variants are more common in autism.
One family in the autism group has a particularly interesting family tree, however. Two brothers, both diagnosed with autism, each carry the same two APBA2 variants. Their mother carries one of the variants, and their father the other, but neither parent has autism.
"Our hypothesis is that one event is not sufficient to give rise to autism, but having both is sufficient," Kumar says. "But at this point, it's still speculative."
Taken together with older studies, the results suggest that APBA2 is a good candidate gene for autism, he says, and deserves further study.
References:
Christian S.L. et al. Biol. Psychiatry 63, 1111-1117 (2008) PubMed
Kirov G. et al. Hum. Mol. Genet. 17, 458-465 (2008) PubMed
Sano Y. et al. J. Neurosci. 29, 5884-5896 (2009) PubMed
Miracle of Brain Wave Vibration therapy in Rett syndrome: Video
Story of Annette: A Rett angel
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Stem Cell Debate: Video 1
Doctor Shocks Oprah with News of Ethical Stem-Cell Successes
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Enriched environment improves symptoms of Rett
Kelly Rae Chi
Oct, 2009
Giving mouse models of Rett syndrome access to toys, wheels and contact with other mice rescues motor skill and other deficits characteristic of the disorder, according to results presented in a poster session Wednesday at the Society for Neuroscience meeting in Chicago.
Rett syndrome, which occurs mostly in girls, is marked by an apparently normal infancy, followed by a progressive deterioration of motor, social and intellectual skills beginning in early childhood. Children with Rett syndrome often show autism-like behaviors in the syndrome's early stages.
A decade ago, researchers discovered that mutations in the MECP2 gene lead to Rett syndrome and, in 2002, scientists created the first mouse model of the disorder.
Exposing Rett mouse models to an enriched environment has, in previous studies, produced mixed results. For example, in a study published last year, researchers gave mice access to toys, wheels and other mice starting at 4 weeks of age, shortly after being weaned from their mothers. The researchers found that the enriched setting improves motor skills in female mice, but not in males1.
Levels of brain-derived neurotrophic factor, or BDNF — a gene target of MECP2 that's thought to be important for learning and memory — does not increase in the male mutant mice but does in the females.
To investigate the benefits of an even earlier intervention, scientists gave Rett mice access to tubes and wheels, and to other mice, including their mothers, beginning at 10 days after birth.
At 30 days, mutant mice in the enriched environment have better motor skills than those kept in standard cages, and they learn tasks as easily as normal mice do. The intervention also ups BDNF levels, but not quite to the level of control mice in the enriched setting, the researchers found.
"In our hands, it worked. Starting early is key," says lead investigator Maurizio Giustetto, a professor of anatomy at the University of Torino in Italy. His group collaborated with Tommaso Pizzorusso of the Consiglio Nazionale delle Ricerche in Italy.
Using high-resolution microscopy, the group looked closely at synapses, the connections between neurons, to asses the proportion of excitatory synapses to inhibitory ones. An imbalance between the two kinds is thought to underlie Rett syndrome and autism.
Mutants given enriched settings have higher numbers of excitatory synapses compared with untreated mutants, the team found; the number of inhibitory synapses does not change. Analyzing the electrical activity of neurons, the group also found that enrichment improves the strength of the connections between neurons, a process important for learning and memory.
The group has thus far analyzed brain slices in a dish, but they plan to develop methods to examine the cells and circuits in whole animals.
References:
Kondo M. et al. Eur. J. Neurosci. 27, 3342-3350 (2008) PubMed
Note: Click on the title to read the Full article
Oct, 2009
Giving mouse models of Rett syndrome access to toys, wheels and contact with other mice rescues motor skill and other deficits characteristic of the disorder, according to results presented in a poster session Wednesday at the Society for Neuroscience meeting in Chicago.
Rett syndrome, which occurs mostly in girls, is marked by an apparently normal infancy, followed by a progressive deterioration of motor, social and intellectual skills beginning in early childhood. Children with Rett syndrome often show autism-like behaviors in the syndrome's early stages.
A decade ago, researchers discovered that mutations in the MECP2 gene lead to Rett syndrome and, in 2002, scientists created the first mouse model of the disorder.
Exposing Rett mouse models to an enriched environment has, in previous studies, produced mixed results. For example, in a study published last year, researchers gave mice access to toys, wheels and other mice starting at 4 weeks of age, shortly after being weaned from their mothers. The researchers found that the enriched setting improves motor skills in female mice, but not in males1.
Levels of brain-derived neurotrophic factor, or BDNF — a gene target of MECP2 that's thought to be important for learning and memory — does not increase in the male mutant mice but does in the females.
To investigate the benefits of an even earlier intervention, scientists gave Rett mice access to tubes and wheels, and to other mice, including their mothers, beginning at 10 days after birth.
At 30 days, mutant mice in the enriched environment have better motor skills than those kept in standard cages, and they learn tasks as easily as normal mice do. The intervention also ups BDNF levels, but not quite to the level of control mice in the enriched setting, the researchers found.
"In our hands, it worked. Starting early is key," says lead investigator Maurizio Giustetto, a professor of anatomy at the University of Torino in Italy. His group collaborated with Tommaso Pizzorusso of the Consiglio Nazionale delle Ricerche in Italy.
Using high-resolution microscopy, the group looked closely at synapses, the connections between neurons, to asses the proportion of excitatory synapses to inhibitory ones. An imbalance between the two kinds is thought to underlie Rett syndrome and autism.
Mutants given enriched settings have higher numbers of excitatory synapses compared with untreated mutants, the team found; the number of inhibitory synapses does not change. Analyzing the electrical activity of neurons, the group also found that enrichment improves the strength of the connections between neurons, a process important for learning and memory.
The group has thus far analyzed brain slices in a dish, but they plan to develop methods to examine the cells and circuits in whole animals.
References:
Kondo M. et al. Eur. J. Neurosci. 27, 3342-3350 (2008) PubMed
Note: Click on the title to read the Full article
Stem cells in Rett syndrome
Beike - Laura
NAME: Laura
COUNTRY: Romania
AGE: 7
DIAGNOSIS: Rett Syndrome
REASON FOR COMING FOR TREATMENT:
Laura was born with Rett Syndrome, a rare genetic disease that causes a neurodevelopmental disorder which is marked by loss of purposeful use of the limbs, balance difficulties and language and socialization developmental problems similar to Autism. Like other children with Rett Syndrome Laura seemed like a healthy child for the first year of her life. By the time she was one year old, she was starting to talk and was able to move around by herself. However in the second year of her life, she started to regress. Both her motor and linguistic skills started to get worse and Laura largely lost most of the abilities she had learned.
TREATMENT: Umbilical cord stem cell and nerve growth factor injections with rehabilitation therapy
BEFORE THE TREATMENT:
Before the treatment started, Laura's condition was similar to that of a highly autistic child. She no longer used the words she had previously learned, and did not respond to other people who talked to her. Her parents felt that she had lost all her linguistic skills and that her memory was very poor. Along with the linguistic deficiencies, she had many motor control problems as well. Her balance became worse and worse and she started to constantly make stereotyped motions with her hands. She could not walk without help, and could not move up stairs or inclines at all.
AFTER THE TREATMENT:
After coming to China twice for stem cell treatments Laura's parents believe her condition greatly improved. They believe physically her balance became much better. She could stand with less of a wide stance, could walk on her own for short distances and could walk up stairs and incline with a little help from her parents. Linguistically and mentally Laura also made great progress. She began to start speaking a few words and became more responsive when other people were talking to her. They also felt her memory improved greatly and she could recognize people that she had seen before.
NAME: Laura
COUNTRY: Romania
AGE: 7
DIAGNOSIS: Rett Syndrome
REASON FOR COMING FOR TREATMENT:
Laura was born with Rett Syndrome, a rare genetic disease that causes a neurodevelopmental disorder which is marked by loss of purposeful use of the limbs, balance difficulties and language and socialization developmental problems similar to Autism. Like other children with Rett Syndrome Laura seemed like a healthy child for the first year of her life. By the time she was one year old, she was starting to talk and was able to move around by herself. However in the second year of her life, she started to regress. Both her motor and linguistic skills started to get worse and Laura largely lost most of the abilities she had learned.
TREATMENT: Umbilical cord stem cell and nerve growth factor injections with rehabilitation therapy
BEFORE THE TREATMENT:
Before the treatment started, Laura's condition was similar to that of a highly autistic child. She no longer used the words she had previously learned, and did not respond to other people who talked to her. Her parents felt that she had lost all her linguistic skills and that her memory was very poor. Along with the linguistic deficiencies, she had many motor control problems as well. Her balance became worse and worse and she started to constantly make stereotyped motions with her hands. She could not walk without help, and could not move up stairs or inclines at all.
AFTER THE TREATMENT:
After coming to China twice for stem cell treatments Laura's parents believe her condition greatly improved. They believe physically her balance became much better. She could stand with less of a wide stance, could walk on her own for short distances and could walk up stairs and incline with a little help from her parents. Linguistically and mentally Laura also made great progress. She began to start speaking a few words and became more responsive when other people were talking to her. They also felt her memory improved greatly and she could recognize people that she had seen before.
Sunday, January 17, 2010
Parent Interview on Rett syndrome
Dear All,
Posting an interview of Ingrid Harding, Founder and President of Girls power 2 Cure, who has a Rett Angel in her life and doing great job for raising more Awareness of this cause. She was interviewed by Anne Ebeling for a story on Girl Power 2 Cure and Rett Syndrome with Parents TV last Fall.
Please watch this interview by clicking on the title and share it with all your friends and relatives.
Love, Hugs, Prayers,
Rajni Khajuria
Posting an interview of Ingrid Harding, Founder and President of Girls power 2 Cure, who has a Rett Angel in her life and doing great job for raising more Awareness of this cause. She was interviewed by Anne Ebeling for a story on Girl Power 2 Cure and Rett Syndrome with Parents TV last Fall.
Please watch this interview by clicking on the title and share it with all your friends and relatives.
Love, Hugs, Prayers,
Rajni Khajuria
Sunday, January 10, 2010
Vote for Reverse Rett syndrome Video
Please vote for Reverse Rett syndrome video
Title: Reverse Rett Syndrome - Give Our Girls A Voice
Share it with all and tell others also to vote for this cause
Link: http://extraordinarymeasuresthemovie.com/?videoId=111
Thanks, Regards, Prayers,
Rajni Khajuria
Title: Reverse Rett Syndrome - Give Our Girls A Voice
Share it with all and tell others also to vote for this cause
Link: http://extraordinarymeasuresthemovie.com/?videoId=111
Thanks, Regards, Prayers,
Rajni Khajuria
Pharmacology and Genetics of Autism: Implications for Diagnosis and Treatment
Article by
Zoran Brkanac; Wendy H Raskind; Bryan H King
Personalized Medicine. 2008;5(6):599-607
NOTE:Click on the link to read full article
Zoran Brkanac; Wendy H Raskind; Bryan H King
Personalized Medicine. 2008;5(6):599-607
NOTE:Click on the link to read full article
Effect of Topiramate on Seizures and Respiratory Dysrhythmia in Rett Syndrome
Article by
Monisha Goyal MD; Mary Ann O'Riordan MS; Max Wiznitzer MD
Note: CLICK ON THE TITLE TO READ THE FULL ARTICLE
Monisha Goyal MD; Mary Ann O'Riordan MS; Max Wiznitzer MD
Note: CLICK ON THE TITLE TO READ THE FULL ARTICLE
Rett Syndrome: Long-Term Clinical Follow-Up Experiences Over Four Decades
Article by
Bengt Hagberg MD, PhD
CLICK ON THE TITLE TO READ THE FULL ARTICLE
Bengt Hagberg MD, PhD
CLICK ON THE TITLE TO READ THE FULL ARTICLE
Rett Syndrome: Model of Neurodevelopmental Disorders
Article by
Alan K. Percy MD; Jane B. Lane RN, BSN
CLICK IN THE TITLE TO READ THE FULL ARTICLE
Source: MEDSCAPE MEDICAL NEWS
Alan K. Percy MD; Jane B. Lane RN, BSN
CLICK IN THE TITLE TO READ THE FULL ARTICLE
Source: MEDSCAPE MEDICAL NEWS
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