If you haven't been keeping up, we flew in to Bethesda MD on Sunday afternoon last week to take part in the National Institutes of Health's Undiagnosed Disease Program. We almost didn't get to fly out due to Hurricane Sandy but by God's grace the flight did not get canceled so we got into town just in time before the storm hit. Getting in was pretty intense (entering involves car searches and major security measures because we were visiting a government compound basically). After arriving, we found out the NIH had to close down for Monday and Tuesday due to the DC area's metro train system shutting down.
|Arriving at The Children's Inn|
|A rainy 2 days (the view out our window of the Clinical Center)|
Early Wednesday we were all admitted and that's when the real hurricane hit! We met Mason's team (the biggest blessing of the whole trip were the people on our team--they were the most kind-hearted, dedicated, interested, thorough medical pros we have ever had the pleasure to know!!...from sun-up to sundown, the boys were their "patients of the week" and we've never experienced anything like the sole focus we were given! We are used to seeing docs once a day on rounds. This team worked tirelessly ALL DAY with us, asking questions, seeking input, nonstop trying to get in histories, physicals, tests that were originally planned plus adding new ones on the spot as the need came up, with results to most immediately available (not the genetic stuff of course, but almost everything else...) -- basically getting everything done we could physically do in 3 days, with barely a moment to spare even to sit for a snack or drink ;) So...despite being exhausted and stressed to the max...it was an AMAZING week and unforgettable and even if we never learn another thing from the trip, we gained invaluable direction and insights that will help us for years to come. Here are some of the things we did...and what we learned...
|Treat in the mail every day!!|
|Clown nose from the mailbox!|
BOTTOM LINE: The concern level for progressive neuromuscular conditions is much lower for Micah! Micah's biggest issue is probably a connective tissue disorder - a hypermobility syndrome that does not appear to be a milder version of what Mason has, but rather a separate syndrome that is a more severe presentation of the loose joint condition I have. Since we dont know the source of the hypermobility yet (skin biopsies can help), we don't know if it will get worse or if it affects other organs besides ligaments/joints/soft tissue or not, but it's possible it could improve as he grows. He will need intense PT and probably OT all his childhood and probably longer to maintain muscle strength needed to compensate for the laxity so he can keep up with his peers better. It does not affect his intelligence one bit and he is a very smart little guy :) We'll keep an eye on his thyroid/autoimmune/muscle issues and see a GI dr. and physiatrist for better orthotics and management.
Yes, Mason also has the profound hypermobility issues that Micah has, plus a lot more...a difficult "double whammy" they said, but the general impression is that he doesn't have a "worse" presentation of the hypermobility, just that he has laxity of tissues in combination with some other worse genetic condition on top of it. The search is on for what has caused that "other" condition. They are hoping that condition was a random event (not inherited). Here is their testing approach for Mason:
1. Test for KNOWN single gene mutations that cause syndromes SIMILAR to what he has (he has features of these conditions but not "typical appearance or presentation"). These tests have already been sent out, awaiting results, and include mutations for CHARGE syndrome and Rubenstein-Taybi syndrome. Tests are also being sent for Congenital Disorders of Glycosylation (because the Dandy Walker malformation of his brain alone should not cause epilepsy or such profound muscle affects as Mason has). They haven't ruled out mitochondrial disease. They will also test my blood for "x-inactivation" issues (this one is too complicated to explain in the blog but you can google it if you have interest.)
2. If none of the known conditions pan out, research will begin to test for new conditions. We already know Mason is missing 14 genes on chromosome 17. But everyone has two copies of genes on the numbered (autosomal) chromosomes, one set from each of their parents. Usually, missing one set of genes just makes you a "carrier" for problems unless the condition is DOMINANT (you only need to have one missing or mutated causative gene to create the disease). It may be that the hypermobility issues are related to the deletion as a DOMINANT condition...but it's only when BOTH sets of genes are missing or mutated that you have big problems because then the body has nothing to compensate for those missing or damaged gene products. Because Micah and I carry the same deletion, it's unlikely the cause for his syndrome by itself. But if Brian has a mutation on one of those same 14 genes that Mason is already missing, and he gave him his mutated gene from the same area as the deletion I gave him, that would create a new autosomal recessive condition never before seen. We would then be going back to NIH for more research to characterize this new syndrome.
3. If there are no new conditions related to the deletion, testing will expand using a newer process called whole genome exome testing. In other words, every gene that produces proteins in the entire body will be systematically checked for mutations and compared to Micah's and mine to try to locate the cause of his syndrome. This is a a very expensive and inaccessible test to most people right now so to have this freely available if needed is an overwhelming blessing!
Besides the genetic testing in progress (which could take weeks to years to lead to any answer...but we will now be in the program as long as it exists and will be followed indefinitely in the event similar cases inform ours as the years go by)...an amazing collection of clinical data was collected this week. We know a TON of new things about Mason including:
- he has a cleft/bifid tongue and many other "midline defects" that will help them understand the biological cause of his syndrome
- he can't turn his eyes outward either way to look to the sides much ("Duane syndrome" of the eyes) which along with his limb defects helps them have clues as to what genes to look at first
- he has blocked tear ducts causing his constant eye discharge (earlier we were told the ducts weren't blocked) which can be treated but may need multiple probing attempts to clear
- he has an ectopic posterior pituitary gland (the back part of his pituitary gland is in the wrong place in his brain) and pending testing may show if any hormones are affected
- his brain is laying down white matter and insulating the nerves (aka things are getting better not worse, but just slowly!!!!)
- he doesn't really have any sinuses to speak of yet
- he has central and peripheral components to his hearing loss and needs a ct scan of his temporal bones in his ears to help with characterizing things better
- he may also have Hirshrung ultrashort segment disease of his GI system and needs further testing including colonoscopy (they really wanted us to stay at least another week to get all this done but logistically it wasn't practical right now for us to stay longer)...they also gave a wonderful new wound wash product and barrier cream for his gtube site/granulation tissue that is neither steroid nor burning like silver nitrate and works GREAT. They also gave better tips for venting...
- he has asymmetry of his chest and back and rotation of his ribs for further clues
- he has a small liver
- he needs further testing to find out the anatomical reason for his frequent UTIs and a plan for prevention (even boys w/o any functional immune systems dont get recurrent UTIs so there must be a bigger reason than immunity or dirty diapers)
- we need some new doctors including a complex care pediatrician to coordinate his testing and treatments, kidney doctor, physiatrist (a rehab medicine dr to coordinate and manage equipment and assistive tech needs), and maybe new neurologist
- he still swallows without aspirating and needs desperately speech therapy added to his regime
- we were given a new vibration toy for him to learn to hold things/desenstize some defensiveness
- He may not outgrow his immune deficiency but he is on a good treatment already for it (IgG infusions). They found out he makes plenty of B cells but they need to figure out why those B cells aren't producing antibodies IgG, A or M and what other components there are to his issues.