WAGR Wednesday~Why Care that We are Rare?

This week, for WAGR Wednesday, I thought I’d highlight the fact that Rare Disease Day 2014 is this Friday, February 28^th.  But what does that mean?  Why is Rare Disease Day important? 

Prior to having a daughter with a rare disease, I probably would have asked the same question.  I would look around at all the diseases that exist, (just talking about the different types of cancer can boggle the mind), and I would think, “Why is RARE disease so important that we have to take a day aside to recognize it?”

It’s more than the fact that for the first few years of Evie’s life, whenever we had to run to Urgent Care or the ER where the doctors didn’t know her, I often felt like the side show at a circus: 

Step inside and see the girl with no irises!

Can you believe it folks?  She’s shows no facial expression because she can’t smile due to the neuropathy from her chemotherapy! 

Look at this, Ladies and Gentlemen; she has a temperature of 97.1 degrees Fahrenheit AND has a raging case of pneumonia!

It’s more than the fact that we had to wait for months to get her approved for Medicaid because they had to research WAGR Syndrome before approving her; AND we had to go through a court of appeals AND have Disability Rights Wisconsin argue on her behalf to get her into a county assistance program, because it’s hard to prove certain things when there is little documentation regarding the extent of the “effects” of WAGR.  

The importance of Rare Disease Day extends far beyond those reasons.   

Rare Disease Day is important because there is very little money invested in the research of, and treatment of rare disease.  Big pharmaceutical companies aren’t non-profit businesses; so why would they think it’s important to create a medication for a small population of people worldwide?  It’s also hard to convince the doctor, who needs some publications under his or her belt, to spend time researching a disease that would be difficult to recruit participants for, would be costly, and would not likely lead to mind-blowing revelations regarding the general human race. 

Rare Disease Day is important because ALL of the rare diseases combined become a unified voice of clarity.  

We ARE important.

We CAN make an impact.

We DO matter to the general population, because the RARE genes that make up RARE disease hold the secret answers to the medical questions which have baffled scientists and doctors for ages. 

For example, the research on WAGR/11p Deletion Syndrome that has been taking place at the NIH has already yielded amazing results like identifying and reinforcing the knowledge of the correlation between obesity and the deletion of the BDNF gene (accessible at:  http://www.wagr.org/obesitybdnf.html).  

  

The research has also shown that many people with WAGR/11p Deletion are missing, or have an under-developed pineal gland, which produces hormones that help regulate sleep.  Knowing that there may be a decreased release of melatonin (one of the functions of the pineal gland) in persons with WAGR/11p Deletion, and that oral melatonin supplements can help them sleep is critical in enhancing their lives.  After all, chronic sleep deprivation isn’t fun for ANYONE!

So, to help show law-makers, researchers, and large pharma companies that rare disease IS important and serves a larger population than they seem to believe, we celebrate Rare Disease Day.  To help our communities, friends and relatives understand that; yes, we have valid struggles, and yes, we have justified hope…we celebrate Rare Disease Day.  To help our rare families around the world feel connected to others; to say, “You are not alone,” we celebrate Rare Disease Day.

Finally, to help me live out MY passion; which is making a difference in this world~to this world; to show the world that BEAUTY can be born from HEARTACHE…

...I will CELEBRATE Rare Disease Day…

Will you?

Et Cetera~Part V

I have now been writing for four days about the "et ceteras" of WAGR Syndrome.  "And other things..." is what et cetera means.  So today I'll talk about the other things such as obesity and high pain tolerance. 

Wait, Tammie, weren't you just going to talk about the four letters that make up the WAGR in WAGR Syndrome? 
 
Not quite. 
 
As more and more parents were able to connect over the internet beginning 20 years ago or so, they started to realize that their children with WAGR exhibited more in common than just the W-A-G-R.  A few of the amazing leaders who formed the International WAGR Syndrome Association decided to create a MedQuest.  It was a questionnaire for other families with WAGR to fill out so there could be some statistical data to present to medical professionals and researchers. 

Yes, you read that correctly, it was the parents of individuals with WAGR who did this.  I stand in awe of these parents every day and marvel at where we would be without them.
 
The results of the MedQuest got the attention they were hoping for.  To make a long story short, it generated enough excitement for pediatric endorcrinologist at the National Institutes of Health to start a study on WAGR Syndrome.  As phase one of the study progressed and the data was being compiled, the similarities of persons with an 11p chromosome deletion were so striking that the study's name was changed to the WAGR Syndrome, 11p Deletions, and Aniridia Study.  In the first few years some interesting discoveries have been made, and some have been published and/or presented at one level or another. 
 
One such discovery was the high correlation between a particular deleted gene and obesity in the patient.  The name of the gene is the Brain-Derived Neutrophic Factor (BDNF for short, but you can memorize the full name and dazzle your friends and acquaintances at cocktail parties and tailgating events...)  According to the NIH,

Expression of this gene is reduced in both Alzheimer's and Huntington disease patients. This gene may play a role in the regulation of stress response and in the biology of mood disorders. [provided by RefSeq, Jan 2009]  Accessed 1/8/13 at http://www.ncbi.nlm.nih.gov/gene/627

Playing at The Children's Inn at the NIH

Interesting...it regulates stress response and is part of the biology of mood disorders.  Hmmm...didn't I mention in my last post that Evie has "off the chart" anxiety and has trouble dealing with homework and learning new things?  Hmmm...

If you're not much into "science" but still like to read about these things in layman's terms, you'll find a great article on BDNF at the Livestrong website  http://www.livestrong.com/article/214646-brain-derived-neurotrophic-factor-exercise/ .  According to this article, BDNF "plays a key role in how easily your brain can adapt to and learn how to effectively complete new challenges, called neuroplasticity."  Well, hot-diggity...I think we're on to something.

But what does this have to do with obesity? The BDNF and obesity weren't really connected until the study at the NIH for 11p Deletions.  Guess what?  For all you research buffs out there, I actually found the article from the New England Journal of Medicine about the WAGR/11p Deletion, BDNF deletion and Obesity.  Check it out:  http://www.nejm.org/doi/full/10.1056/NEJMoa0801119 . 

For some reason, on some level, knowing that we participated in this study and it yielded such important results makes me feel like a celebrity.  Look out, Miley, your chain just broke on your wrecking ball, make way for the double helix (that's just some biology humor).

Sleep Study at the NIH

I'll sum up for you the findings of the study:  By 10 years of age, 100% of the patients with heterozygous BDNF deletions (95% confidence interval [CI], 77 to 100) were obese (BMI ≥95th percentile for age and sex) as compared with 20% of persons without BDNF deletions (95% CI, 3 to 56; P<0 .001="" font="">

Now I would call that a pretty darn strong connection between the BDNF gene deletion and obesity.  We parents struggle and struggle to help keep our children out of that "obese" bracket, but it is extremely difficult.  We don't WANT to deny our children the right to candy, chips and ice cream any more than anyone else does, but sometimes we have to be more vigilant than other parents.  It's VERY difficult to do when society rewards children ALL THE TIME with food!  I recall a parent once saying, "I want to hang a sign around [my child's] neck that says, 'I know I'm cute, but please don't feed me.'"  We've had to crack down on Evie's calories and try to encourage physical activity, but it has to be a family lifestyle for us.  I don't want to preach to her about staying healthy and then not follow my own advice.

Believe it or not, BDNF is tied to another common characteristic in our loved ones with WAGR; high pain tolerance, or at least a different way of perceiving pain.  I'll quote the article and then explain it in my terms.

Patients with BDNF [deletion]... had lower pain scores than patients with intact BDNF...suggesting impaired nociception similar to that described anecdotally in the case reports of a child with a chromosomal inversion of the BDNF region...These data are consistent with results of studies in mice that suggest that BDNF plays a role in the modulation of pain sensation. (Citation from http://www.nejm.org/doi/full/10.1056/NEJMoa0801119 ).  



Double IV's during the NIH Study Stay

Let me give you an example of Evie's pain threshold.  A few years back Evie was stung by a bee on her right hand.  She cried a little, we put ice on it, and then we headed off in the car for Detroit, Michigan for WAGR Weekend (I mean, when WAGR is so rare, you never want to miss a chance to hang with your WAGR peeps for a weekend.)  We got to WAGR Weekend without incident, but when we woke the next morning Evie's had was swollen, hot to the touch, and reddish with purple blotches.  Now you or I would avoid using that hand, but not Evie.  She was opening doors, feeding herself, writing, and coloring with her right hand!  A trip to the ER confirmed that she had a staph infection.  If you've ever had any infection, you know that this had to be painful, yet Evie showed no distress concerning her hand. 

Oddly enough, once we started Evie on occupational therapy, she started to perceive pain more like a "typical" person.  That was good and bad.  It was good because a high pain threshold can be dangerous.  For example, Evie wound up with a horribly burned hand when she was 3 years old because she had held it on a hot oven door and didn't respond to any sort of pain stimulus.  Now that she processes pain more normally, she dreads having a blood draw, and actually cries when she is hurt.  It breaks my heart to see her fear and pain, but I know that it's better for her to respond to,and accurately process pain in the long run. 

So you see, there is still more to WAGR than just W-A-G-R.  Here I've identified the high incidence of obesity, and the high pain tolerance expressed by a great majority of our loved ones with WAGR/11p Deletions.  Tomorrow I think I'll tackle Sensory Processing Disorder (SPD).  You'll hear about head-banging, biting and hair-pulling (oh, my...), and find out how many of our families have found successful ways of dealing with SPD through occupational therapy.