Summer 2016 Newsletter Excerpt – Join CDO today and read our full issue

Join CDO today – www.chromodisorder.org – to read the full Summer 2016 newsletter issue and support rare chromosome disorder awareness at the same time.

Inclusion: An Accessible Theme Park – Adreanna Tarwater CDO Director 

We are so fortunate to live in San Antonio where we can spend the day at Morgan’s Wonderland. Morgan’s Wonderland is the world’s first totally accessible theme park.  A father, Gordon Hartman, built the park after seeing his daughter, Morgan, struggling to play with other children.  He had a dream where children like Morgan could play next to other children and be totally included.  He made that dream a reality for so many families by building Morgan’s Wonderland.

There are so many places that we go as a family where our son, Nathan, is excluded. He is non-mobile and is not able to sit, so a lot of theme parks are out because he is excluded from the rides. At Morgan’s, he is able to rideall the rides along with his siblings.  Every ride/activity has been modified so that no child/adult regardless of need is excluded. Our Nathan’s favorite ride is the train.  He loves the swaying of the cars and especially thinks it is funny when the Conductor blows his horn. I n addition to the train, Morgan’s Wonderland has a ferris wheel, jeeps, swings, play-sets, and a carousel that are all wheelchair accessible.  They even have a sensory center, waterfeature area, and  outdoor music pavilion.  The super exciting news is that next summer they will be opening the world’s first accessible water park.  The most exciting part is that even children/adults in wheelchairs will be able to ride/play in the water park.  Make A Wish grants trips to Morgan’s.  Project Angel Fares also works to get adults and children to the park.

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Recognizing Potential & Beauty: The Story of Emily – By Kathy Paulsen

Paulsen

When I received my daughter Emily’s diagnosis of a chromosome 5 long-arm deletion nearly 20 years ago, access to information regarding disabilities was minimal. There was no Internet. We had no personal computer. I received one very bleak case study from the genetic counselor, and was told, “She’s still the same person, take her home and love her.”

Of course I did that, but I struggled to do more as the doctor’s words “mental retardation” and “early intervention” echoed in my head. I was desperate for information, for compatriots in this foreign
community, for predictions of what my daughter’s life would be like. My lifeline was my CDO newsletter and parent network. I later discovered Unique, and I subscribed to Exceptional Parent magazine. I received some valuable information, but nowhere did I find a child just like mine. I found myself constantly trying to explain to others what I didn’t even understand myself.

I wish then there had been the uplifting and relatable stories of The Mighty back then, the ability to Google her conditions and to find a few others like her in a Facebook group.  I would have loved to have others’ online cheers for her inchstone successes, and to commiserate over the unique sorrows we faced. It is wonderful that those resources exist today. But she is still rare among the rare. Getting early services was easy, the needs of my verbal but largely unintelligible daughter clear. At 3, she had the developmental abilities of an 18 month old. I was warned that she would likely never learn to read. She started in a pre-primary impaired preschool and received speech, occupational, and physical therapy. I had some guidance and some support. The cloud was lifting.

As we fell into our “new normal,” life became happy again. My initial quest for answers softened into a day-at-a-time perspective. With the help of some excellent teachers and professionals, I could once again have mom as my primary role, putting educator and therapist secondary. And I realized that no child arrives with his or her fortunes foretold. So I could let go of trying to figure out Emily’s future, feel more content with the knowledge that we would be there to give her what she needs, when she needs it. I learned to let Emily be my guide for many things. I learned, as parents do with all children as they raise them, to interpret her body language and temperament. With her clues, I could avoid most crises and melt-downs. She knew more than anyone what she could do. My role was to coax and encourage, watch and listen.

There were, however, battles. Battles with insurance companies, with school personnel, and yes with my husband and with myself. Battles to get people to listen to information about a disability that has no syndrome name. Battles to be seen as the authority on Emily by the doctors charged with treating her. Battles to get school administrators to address bullying. Battles within myself to ignore the judgments thrown our way from friends and strangers alike when they would witness things they did not understand, and to figure out when to respond or explain. Battles to answer questions with elusive answers: what surgeries and treatments, what therapies, am I doing too little or too much, how much do we push her academically? Socially? Physically? How do I keep her identity and mine separate when our lives are so entwined? And the biggie now: How do I help people understand that disabled and capable are not mutually exclusive?

As we begin the journey to navigate Emily’s life as an adult, the lack of clarity persists. Organizations and individuals want proper labels for her, but they don’t exist. Maybe it’s a human tendency, to create neat categories to put folks into? Emily doesn’t fit into any easy category and never has. She did indeed learn to read. It took 6 years, but she hasn’t stopped since. Against all odds, she finished high school with a true diploma and now attends classes at community college. She delights in working with the 3 year olds at the Easter Seals preschool where she volunteers. She enthusiastically cheers for her Special Olympics swim teammates and gives her all to the sport. She has gifts and talents and loves putting them to use. She has a heart and soul that inspires all of us who know her to be better people. She has persistence and perseverance, creativity and kindness. But she also needs help crossing the street safely, buttering a piece of bread, and brushing her hair. She has very serious medical issues and real disabilities including developmental, vision and speech impairments.

I still struggle with how to explain her chromosome deletion to new people. Maybe that’s better. If I had a tidy label that people widely understood, in their own way, it would not tell the whole story of who she is. I would name the condition and people would think that’s her. It’s not. Not for anyone. We are each a messy array of personality traits, strengths and weaknesses, abilities and deficits. This array is impossible to fully discern from outward appearance or generalized category. Perhaps this understanding is one of Emily’s greatest gifts to me, recognizing potential and beauty in every individual.

Perspectives for Treatment of Chromosome Disorders

PERSPECTIVES FOR TREATMENT OF CHROMOSOMAL DISORDERS

Chromosomal disorders are conditions where, as a result of deletions or
duplications of some chromosomal segments, the organism experiences the excess or absence of a significant number of genes. Manifestations of chromosomal disorders include both morphological defects caused by the abnormal action of genes during embryonal development and functional abnormalities (seizures, hypotonia, aggression, hyperactivity, sleep disturbances, etc.) caused by the constant abnormal action of genes. When we use the term “treatment of chromosomal disorders” we talk about attempts to alleviate functional abnormalities and give patients a better chance to live independently. It is obvious, however, that morphological defects which occur during embryonal development cannot be restored by any drugs.

The existing attempts for treatment of patients with chromosomal
abnormalities may be subdivided into several groups. The potentially most fundamental methods have a goal to restore a normal karyotype or inactivate the action of excessive genes. One strategy involves inactivation of one of the chromosomes 21 in a trisomic patient with Down syndrome. One of the human genes – gene XIST –
inactivates one of X-chromosomes in females. The XIST gene prevents
transcription of the genes on the X-chromosome. If this gene is inserted into one of chromosomes 21 in a patient with Down syndrome, this chromosome will became inactivated, restoring the normal “disomic” condition. Currently the experiments with inactivation of excessive chromosomes are in the “embryonal” stage; if these tests provide good results in laboratory animals, this method will be tested with clinical trials. Although currently XIST-strategy is studied only for
cells with trisomy 21, the same method may be promising for other trisomies as well.

Some types of chromosomal pathology (ring chromosomes, additional
markers, dicentric chromosomes) are relatively unstable. Most patients with these abnormalities have both a clone with an abnormal chromosome and a normal clone. Generation of pluripotent stem cells from the skin cells of a patient with ring chromosome 17 has shown that reprogrammed cells lost the abnormal chromosome 17 and duplicated the wild-cell normal homologue. If this is true for other ring chromosomes and other forms of “unstable” pathology, it will provide an
opportunity to use cellular reprogramming as a way of therapy for certain chromosomal disorders.

A strategy of reprogramming as well as XIST-strategy, however, will (or
may) cause uniparental disomy – a condition when both homologues chromosomes are identical (i.e. two copies of the same maternal or paternal chromosome). If this chromosome carries an autosomal-recessive gene, the patient (or reprogrammed cells of the patient) may become homozygous for this gene.

Other methods for treatment of chromosomal pathology seem to be not so fundamental by nature but more achievable. Down syndrome for instance is a condition where several attempts for treatment of patients with this pathology have been made.

It is well known that the size of the cerebellum in persons with trisomy 21 is significantly less than in persons with a normal karyotype. As a result there is a considerable impairment of cerebellar function in patients with Down syndrome. In the experiments with a specific line of mice Ts65Dn (widely used as an animal model of Down syndrome) the newborn animals who received a stimulation by “Sonic hedgehog” – a growth factor involved in different aspects of development -show both an increase of the size of cerebellum and an improvement of its function. Mice “treated” by “Sonic hedgehog” show an ability to learn their way around a maze – an indicator of function of learning and memory. The idea of early intervention seems very plausible, but there is still a long way to go between experiments with rodents and the clinical usage of “Sonic hedgehog” (or other growth factors) in treatment of Down syndrome.

Experiments with the mice Ts65Dn show that these animals demonstrated excessive inhibitory brain activity. Release of this inhibitory effect may improve cognitive function. One way to reduce this inhibitory effect is to block the activity of GABA – the primary inhibitory neurotransmitter. There are experiments where
Ts65Dn mice were chronically treated with a negative allosteric modulator of GABA RO4938581.

It has been shown that this treatment improves the functional and neuromorphological deficit in a mouse model of Down syndrome. Currently there are some clinical trials ongoing to test this kind of treatment in adult patients with Down syndrome.

An examination of the brains in Down syndrome patients has shown a remarkable similarity between these brains and those in persons with
Alzheimer syndrome. Most Down syndrome patients develop Alzheimer-like plaques and dementia in their 40s. Persons with Down syndrome have high levels of myoinositol – a chemical related to cognitive impairment and involved in formation of plaques in the brain. There is a trial to treat patients with Down syndrome by scyllo-inositol (ELND005) – a drug originally synthesized to break up amyloid plaques in the brains of patients with Alzheimer’s syndrome. The current trial hopes to demonstrate the efficacy of this method for treatment of Down syndrome patients.

There are some publications describing possibility of “pathogenetic”
treatment in other conditions. For example many manifestations of Phelan-McDermid syndrome (deletion of 22q13.3) are caused by the loss of SHANK3 gene, which resides in this area. Neurons of Phelan-McDermid syndrome patients have reduced SHANK3 expression and defects in excitatory, but not inhibitory, synaptic transmission. Treatment of the neurons with insulin-like growth factor I (IGF1) corrects the excitatory function of these cells and shows the pathway to
correct intellectual disability and speech impairment in patients with this disorder.

The more common and more standard ways for treating chromosomal
disorders are related to the replacement of products which are not synthesized in a patient or synthesized at an unusually low level. It is similar to the usage of insulin in patients with diabetes. For example, patients with Klinefelter syndrome have very low levels of testosterone. The administration of testosterone in adolescents with Klinefelter syndrome shows good clinical efficacy in 95% of patients.
Patients with distal deletions of the long arm of chromosome 15 usually reveal significant growth delay, because this deletion involves the gene responsible for synthesis of the growth hormone. The administration of growth hormone significantly improves the growth in these patients. Treatment by growth hormone may be beneficial also for other patients with other chromosomal pathologies experiencing growth delay.

Common drugs for treatment of attention deficit hyperactivity disorder or seizures may be used also for the treatment of these manifestations in patients with chromosomal pathology, although clinical results may vary even in persons with the same chromosomal imbalance.

Dr. Iosif Lurie
Medical Geneticist
CDO Consulting Medical Advisor

Rare Chromosome Disorder Awareness Week is almost here!

Hi everyone –

It is almost here! Rare Chromosome Disorder Awareness Week (RCDAW) begins June 2nd!

Many CDO members are organizing special events this week. We would love to know what you have planned too.   Let us know and we will post to our Facebook pages.

Would you like RCDAW flyers to help spread the word and increase awareness in your neighborhood, town or city?   These can even be personalized to include your favorite photo.   Please e-mail Kelly Paulson – kelly.paulson@chromodisorder.org for the flyer and instructions on how to add your child’s photo.

There is one super easy way to increase awareness this week – just visit our website – www.chromodisorder.org – and download the RCDAW logo and add it to your personal websites and blogs.  We even have the logo available in different languages!

Beautiful CDO awareness t-shirts are also now available – we are offering three different designs along with many other items through our www.zazzle.com/cdo_inc online store.

And in honor of Rare Chromosome Disorder Awareness Week, CDO is giving away free RCDA bookmarks to our members. Please simply send a stamped self-addressed envelope to the address shown below to receive your free glossy bookmark.

Individually each of these chromosome changes is still considered rare. But we are gradually now learning these disorders actually may not be as rare as once believed. Please support Chromosome Disorder Outreach Inc., RCDAW, and our goals of increasing research, education and understanding. Together we are a strong force.

Chromosome Disorder Outreach Inc. P.O. Box 724 Boca Raton FL  33429-0724