A kind-of answer. Maybe.

When you’ve sent out a genetic test knowing that the results will take six to twelve months,  you don’t wait on the edge of your seat for the phone to ring.

When you’re on your sixth genetic test and the results have been “normal” every.single.time., it becomes difficult to anticipate hearing anything but “The results were typical.”

When you’ve been looking for the answer for three and a half years, you don’t really expect one anymore.

And so last Thursday, on the first day of Maya’s summer vacation, while she played with Dave at home and I sat in the waiting room of my obstetrician’s office, the samples that we had sent out for exome sequencing back in December were just about literally the last thing on my mind.  I was waiting not-so-patiently for my glucose test blood draw, thinking about what I would eat when it was done, and mentally composing a to-do list that was roughly 100 items long.  I took out my phone to jot down a reminder and saw that I had new email.  From Dr. Yale.  Which said:

Hi Dana,

Is there a time that we can talk?

I’m on call until tomorrow, tomorrow afternoon would work well for me.

Dr. Yale

If I could have called right then, from the waiting room, I would have.  Tomorrow afternoon?  Really?  It’s difficult to wait for results.  It’s painful to get a hint that seems to say there is an actual result of interest (if there had been nothing found I expected that we would have heard later, rather than close to the six month mark) and I have to wait to hear it.  It’s torture to know that something genetic has probably been found in your child, and you are 6 months pregnant with another child, and now you have to wait another day to hear the results.   

I emailed back requesting an earlier call (and paraphrasing that last sentence in the above paragraph) and Dr. Yale replied that I shouldn’t worry, results were tentative and very unlikely to repeat in a subsequent pregnancy, and that tomorrow afternoon was really the earliest time that he could talk.

So, we waited . . . kind of.  We weren’t about to just waste a day of Maya’s time off sitting around, so we spent a lot of the next day at the mall, and when it was time to take the call about the results I found a quiet corner of Barnes & Noble, settled in, and took rapid notes on my tiny pocket notepad.

Here are the facts, presented for the sciency folks first and then translated for the general population.

Sciency: The research team has a tentative finding.  They found a de novo nonsense mutation.  While they can’t be certain that the finding is causative, the activity of the proteins produced by this gene have appeared to be potentially developmentally significant (as indicated in prior research), making a reasonable case for this mutation being causative in nature.  This mutation has never been documented before.

Translated: The research team has found a mutation that might be significant.  The mutation did not come from Dave or from me, and therefore was totally random and spontaneous, happening some time very shortly after conception.  This means that the chance of it happening again (or the chance of it happening the first time, for that matter) is very close to 0%.  The team cannot be certain that this mutation is the cause of Maya’s developmental delays, but it seems like a solid possibility.

This mutation has never been documented before. 

Ever. 

There is no syndrome name, or support network.  No articles to read or charts to compare.  And so, even with a (possible) answer, we are still in the not knowing.  Still in uncharted territory, perhaps now even more so than before. 

Dr. Yale went on to tell me about further testing that we could do, which would help to determine whether this finding is in fact causative (meaning, is this finding “the answer”, or just a random unrelated thing). 

(We returned to Yale yesterday to give samples for this next round of testing, which will examine the proteins created by this gene.  Many genes code for proteins, and the proteins created by this particular gene have been found to be active during fetal development and early childhood . . . so, if Maya’s instructions for making the protein are garbled, and the proteins are possibly misshapen, it would make sense that development could be affected.  (On the flip side, if the proteins made by this gene have been shown to only be active in, say, the kidneys, we would know that this mutation probably wasn’t linked to global developmental delays.)   This round of tests will likely take a few more months to come back.)

The call ended, we had frozen yogurt at the mall, picked up a birthday present for one of Maya’s little friends, and drove home.   That night, after Maya was tucked into bed, we called and emailed family and gave them the news.  I had forgotten how draining it is to tell, and then retell, medical results. 

The most common question that’s come my way is “how do you feel about it?” 

So far, honestly, I’m not feeling much.  I’ve got a kind of delicious numbness happening, and I know that somewhere beneath it are some good feelings all twisted around some negative ones, and I don’t  feel the need to try to sink into that and untangle it all just yet.  Instead, I’m going to enjoy the rest of my family’s week off.  There’s time for thinking later.

We remain extremely grateful to the people who donated to Maya’s sequencing back in December---your support made this finding possible.  Now we’ll wait to see where it leads.  Thank you.

  

Maya's story is in Bloomberg News

Today was a big day for Maya--she crashed on to the mainsteam news scene.  She appears rather nonchalant about the whole thing, really.  I asked her if she was excited and she used the iPad to say "milk-milk-milk-milk".  So, I guess that's a no.

Several months ago I was put into contact with a reporter from Bloomberg News who was working on a series of stories about genome sequencing.  At the time, we were still in talks with RGI, planning to meet with a doctor sometime in the future about the possibility of genome sequencing.  We spoke with John many times over the next few months, and he came down from Boston to meet Maya (and brought a camera man to shoot some video of her playing and an on-camera interview with me--eek).  We kept checking in as we went to Yale and shared our story here, and then had the fastest fundraising ever.

I kept it a secret, because news seems fickle to me, and I felt like I didn't want to mention it until it was a sure thing.  A really sure thing. 

Today, the article went up on Bloomberg's website.  The first half of the article addresses the potential that genome sequencing has with regard to curing cancer (hence the title), but the second half is about Maya's undiagnosed story.  There are 2 pictures, and then the aforementioned video sequence (which is slightly extreme-close-up for my taste, but overall well done, and I don't sound like a fool, so . . . win, I think.)

Here's a link to the article.

Here's a direct link to the video (which you can also see on the left side of the article). (Also, the video opens with one of my favorite pictures of Maya---her first "real" smile.  So cute.)

And if you're interested in following the series, here's a link to John's first article (posted last week), which was the first in the series.

 

Thank you

In the past 6 hours Maya's fundraising goal has been met.

This has been amazing. 

The texts, instant messages, Facebook messages and phone calls have been coming in, asking if we're watching the page, if we're reloading, if we see the numbers adding up.

Yes, we've been reloading.  Constantly.  Amazed.

Thank you.

Maya's fundraising page will remain up.  Any additional funds raised will go directly to other children who are waiting to have their samples sequenced (not to larger, institute-wide fundraising).  These are kids just like Maya, and they appreciate your support and generosity as well. 

My contact at RGI called me a little while ago to ask if we would be ok with leaving the page up to catch potential extra funds for other kids and we were more than happy to do so.  He also informed me that he had reached out to Dr. Yale to let him know that he should get ready to start sequencing.  He was floored by the speed and generosity of Maya's network.

She's got a lot of people who love her and are cheering her on. 

Thank you.

We've got some medical news (The conclusion)

This post is a continuation of yesterday's post.

So, picking up where we left off:  Six months ago I received a Facebook message from a blog reader which, after a few exchanges, put me in contact with a group called Rare Genomics Institute (more on them later).  They wanted to know if we would be interested in having Maya’s DNA sequenced.  I rolled the information around in my head for a few days before agreeing to the first phone call to discuss it all.

I was interested, but cautiously---DNA sequencing is the next (and maybe final?) frontier of rare disease diagnosis, but is pretty novel, and therefore comes with some uncertainty.  It’s also not yet clinically available . . . meaning that we can’t just go to a doctor and ask them to order the test, we would have to be part of a research trial (which than raises some privacy questions).   There were a lot of questions, phone calls, and emails.  We learned a lot, and our concerns were laid to rest.  We decided to move ahead with figuring out whether we were a match for the research.

Over the next few months, I compiled medical records.  I called hospitals and doctor’s offices, signed releases, and charts began to arrive.  I read the files, kind of awestruck by the sheer number of appointments that we’ve had, many of which I have little to no memory of.   I typed up a summary packet of findings, test results, in-office notations, anything that might be a clue.  I traded emails with my contact at RGI, and later with the doctor that we would (hopefully) be seeing at Yale.  He agreed that we were an interesting case (um . . . thanks?).  And that’s what brought us to Yale last week.

At Yale, we met with Dr. Yale (ok, that might be a fake name), who went over my medical summary packet and talked with us (for nearly 2 hours).  The good news was that he didn’t have any guesses as to what syndrome Maya has.  (Yeah, you read that right.  I hate new syndrome guesses—they stress me out and lead me to google the syndrome and read everything about it, then I cry, then I toughen up and accept it, and then 4-6 weeks later we find out that’s not what she has anyway.  Exhausting.)  We were in the exam room for nearly 2 hours, Maya circling around the room, pulling toys out of my giant toy bag and scattering them.  Dave and I delivered another brilliant tag-team performance, alternating as one of us spoke with the doctor and the other entertained increasingly restless Maya. She wanted to be put on the exam table, then she wanted stickers, then she wanted to rip the paper on the table to shreds, then she wanted to get down, then she was throwing blocks.  She kept sneaking behind the doctor’s chair to bangbangbang on the computer keyboard that was right at eye level.  She was a little tornado, first cycling slowly but then with growing ferocity (and noise) as the appointment went from kind of long to long to too long.  In the end, Dr. Yale thought that Maya was a perfect candidate for exome sequencing.  

An aside on DNA/genome/exome sequencing: 
Your DNA is made up of 6 billion base pairs.  Current clinical genetic testing only looks at a very small portion of the DNA.  Whole genome sequencing would look at basically the entire DNA of an individual, but is extremely expensive (although prices are rapidly dropping) and time consuming.  Exome sequencing involves sequencing only the protein-coding sections (exons) of the DNA.  These exons make up only 1% of the total DNA, but are believed to be responsible for about 85% of disease-causing mutations.

All people have genetic mutations, and most of these mutations are completely harmless.  Because of these harmeless mutations, exome sequencing will turn up over many, many mutations, and scientists will have to work to figure out which ones are meaningless and which ones are possible candidates for causing Maya’s syndrome.  They will need Dave & I to have our exons sequenced as well, so that they can compare her mutations to ours (ex. If Maya has a specific mutation and I have an identical one, it would be unlikely that that mutation is the source of her issues).



So, while at Yale we all had our blood drawn, the samples have been received and are in good shape, and now we wait.  

This is the tricky part.

Someday, exome sequencing (and, likely, genome sequencing) will be routine tests that are available through a geneticist, covered by insurance, just like our microarray and karyotype were.  Both types of sequencing have dramatically dropped in price, and the ongoing research efforts will hopefully demonstrate the necessity of making sequencing routinely available to insurance companies.  However, it will likely be another few years (2? 5? 10?  I've heard different guesses from different doctors) before that happens.  With the help of RGI, we were able to find a doctor and a lab that can sequence our exomes, but there is no grant money that will cover our sequencing, because Maya's uniqueness isn't a perfect match for any of the ongoing funded studies with new patient slots available.   

Bottom line: We have to raise the money to pay for the exome sequencing ourselves.

Dave and I are glad to have partnered with Rare Genomics Institute (RGI) in our quest to find a diagnosis.  They are passionate about helping families with undiagnosed children attain DNA sequencing, and they were able to help us with some of the biggest challenges of the procees: screening to make sure we were good candidates, matching us with the doctor and the laboratory at Yale, and helping us to get the appointment (and to get it pushed up a few months).   And now they have built a fundraising platform for Maya (and, thus far, two other children who are in the same situation).   Their idea is this: rather than having a family try to directly fund DNA sequencing (as families of kids with special needs are typically bleeding money to private therapies, uncovered medical bills, devices, etc) a crowd funding platform is set up.  It allows many people to make small donations that will add up to fund the project. 

We need to raise $2,500 for the exome sequencing (genome sequencing would have been six times that amount).   RGI has set up a fundraising page for Maya, and she has already received some donations from within the scientific community (aka generous strangers who are interested in supporting genetic research).   When the fundraising is complete, the sequencing will begin.  From there, it will likely be a minimum of six months before we hear about any potential findings. 


We’re (cautiously) hopeful that this will be the beginning of the end.



A few notes:

• If you choose to donate to Maya’s fundraising page, we thank you sincerely.   You should know that all donations are tax-deductible and go directly to the funding of Maya’s sequencing project.  The money will go to Maya’s fund at RGI, then will transfer directly from RGI to Yale.  When the money has been received and confirmed by Yale, our sequencing will commence.
• You may notice that we only need to raise $2,500, while the other children on the site are raising $7,500.  This is due to the difference in prices at the hospitals that they are using.  We are the first patients to go through Yale with RGI, and the costs associated with the Yale lab are significantly less than many other hospitals.
• If you have a child who is undiagnosed and are interested in finding out whether RGI could help you with genetic sequencing, the best way to contact them is through the contact form on their website, here.