Saturday, August 16, 2008

Covering the bases

In journalism, this is called burying the lead. In comedy, it's called a delayed punchline. Either way, it goes something like this:

Mo: You really should post a blog update saying Hope is feeling better.

Me: Uh, OK. (Thinking to myself: "Damn, every time we announce Hope is doing well, something bad happens.")

We're not sure this qualifies as good, bad or neither, but two hours after posting about Hope's triumph over Roseola, an envelope arrived from Beaumont Hospital's Genetics Department. Inside was the long-awaited results of her genetics testing.

The short answer: Hope has a mutated gene typically associated with classic Cornelia de Lange Syndrome.

That is the more severe variant of the syndrome that poses more challenges.

Using microarray analysis, a high-tech look at microscopic spots of DNA, researchers at the University of Chicago analyzed one gene. It's called NIPBL. The test essentially checks to see if the sequencing and building blocks of the gene are as they should be.

Attached to the letter were the laboratory results in big bold, upper-case letters is a word we've seen too often and still hurts to see: ABNORMAL.

It's complicated stuff, but the Cliff's Notes version is that genes are recipes for making proteins that, in the formation of life, tell the gooey blob that becomes a person how many amino acids to string together. At first blush, it seems cruel and capricious that one gene among 20,000-40,000 could have such a profound effect: everything from small stature and arched eyebrows to retardation and limb abnormalities.

If she had to have a mutated gene, why couldn't it be the one that makes cilantro taste spicy?

It's not that simple. NIPBL is an important gene. It's something of a regulator that tells other genes how many amino acids to produce. It's not a perfect analogy, but it's almost like a bad Christmas tree light: One blown fuse can dim the entire line.

The other gene associated with CdLS is called SMC1A. Those who have that mutation tend to have a milder form of CdLS and fewer challenges. It's sometimes so mild that parents may not suspect something is wrong until their child is 3 or 4 or older.

We always knew that wasn't Hope. We've debated the severity of her condition -- and still do -- but knew she isn't mild. Geneticists have a checklist for CdLS. Hope has at least a dozen of the indicators.

So we suspected the news was coming, but there's still comfort in uncertainty and a maybe, just maybe sliver of buoyancy that our hunches could be wrong.

They weren't, but the letter brought some relief as well. Our game plan all along to undergoing the test was two-fold: To help the understanding of recurrence of CdLS by participating in a Children's Hospital of Philadelphia study of parents with multiply affected children; and to help ourselves with future pregnancies to maximize our chances of a child without the syndrome.

That could means more tests, perhaps of Will's banked blood and perhaps ours as well. The hope is that by isolating the gene, a fertilized egg could be tested for that gene's mutation before implantation. It's an oddly sterile and slightly creepy concept, but such are the hands we're dealt.

And they're not bad hands at all.

I was sad when I read the letter. We have a better sense of Hope's future than we did yesterday, and it can be scary in its totality. But microarray analysis is a crap shoot: In the best cases with CdLS, they're only able to discover a mutated gene 50 percent of the time. And failure to isolate the mutation changes nothing. It doesn't mean children aren't classic or mild. It simply means they couldn't find the mutation.

In that sense, we're relieved.

I was worried about Mo's reaction. She sighed, whispered "that sucks," and then came home and held our baby.

Hope laughed and smiled. We don't know what the future portends. There's still a range of abilities in classic CdLS. After a few months of stridently checking the development chart, we're now focused on what she can do, not what she can't. And Hope is doing so much and making us so happy that it's impossible not to be optimistic. We named her Hope for a reason.

Mo re-read the letter. It was from one of our favorite doctors. We like him so much because he gives us such great material. Straight from Central Casting as the intrepid, nerdy scientist, he's big on footnotes and thoroughness.

Delivering the news we wish we didn't have to hear, he closed a letter dated Aug. 13 with "With my very best wishes for the Holidays and New Year."

"Well," Mo said, folding the letter. "I'm glad he made sure to cover that base."


Misty said...

.... i know how hard that must've been...we are still waiting on our test results from chicago. i'm sure our results will be the same.. On the check list we went through with our geneticist, Mason checked off ALL but two (limb differences and pstosis)!!

but i know that you know this already. .. our kiddos are shining stars who have brightened our lives beyond imagination..

hope is beautiful! simply beautiful!!!!!!!!! and i think that she is doing wonderfully from what i see and read all the way over here :)

Anonymous said...

Another step on the journey. You must have such mixed feelings, and I'm glad you can see the upside.

I'm also so glad you're willing to share so much of your adventure with the us. Never underestimate the good you're doing in that way!

Lotsa love from Maine --
Grandma K.

Rhonda said...

I'm sure it was hard reading that letter. But, through the clinical terms you don't see the "Hope" terms. My son is 20 years old and there were no tests when he was diagnosed. He was not officially diagnosed until he was 18 months old because he had to "grow into the features". There was no checkliist but we were told that he would be nothing but a vegetable. He would never sit up, talk, walk. Nothing. What a devastating diagnosis to get for your tiny, precious baby. While they were right about some of the things, they were not right about him being a vegetable. He functions mentally in the 24 to 36 month range but he can walk, he can say important words like juice and pudding, he can sign, and he can certainly let us know what he wants in his own type of communication. While it is certainly not the life I envisioned for myself or my child, it is our life and we work hard at making the best of it. I can tell you are doing the same. We all want the best for our children and it is hard when you can't make their pain go away. But, what we can do is make the life they have as good as it can be. Hope will do things on her own terms and her own timetable. You would never think that a 5 year old learning to drink out of a straw would be anything to give a second thought to, yet there we were sitting in our car looking out at the lake and lo and behold that little guy took a big swig right through that straw. If anyone would have seen us they would have thought we were lunatics. We were laughing and screaming and saying "Good job". You learn to appreciate the little things. It certainly isn't an easy journey but it is one I am so proud to be a part of. Good luck with your journey. Thank you for letting us be a little part of it. Have a good week.

Rachelle Riedmiller said...

That must have been a difficult letter to read. We have yet to have Joey tested, but it is something that we are considering, just never had the courage to do. Hope is beautiful and I love keeping up on her life. With Joey, we take it a day at a time, and appreciate him for what he can do and make a huge deal out of the "little" things that he can accomplish. Thanks for sharing your story.

Heidi @ GGIP said...

We are waiting for our test results. Off the top of my head, I named 11 things on the list (don't know if it's the same list).

Louise said...

Hi Joel and Maureen,
Just wanted to tell you that your daughter is beautiful.

~ Louise

Karen said...

That must have been a difficult day.
Ben also has a NIPBL mutation, but we didn't need the test result to tell us he was on the more severe end of the CdLS spectrum. Still, when we got our results, I felt a little sad. Getting the test done was definitely useful for us because we were able to have testing done for a subsequent pregnancy. It would be great to be able to do preimplantation testing.
I think it is still possible to have mild CdLS with a NIPBL mutation. It just depends on how severe the mutation is, and how abnormal the resulting protein is. The genetics counselors you are working with at CHOP would probably be able to tell you more.

Misty said...

Me again! We got our results back today... and Mason does have a mutation in the NIPBL gene... When our Dr. handed me the report, the first thing I saw was the ABNORMAL in big black lettering and I thought of you..and all of the parents who have been in this situation. I knew from day one that mason had cdls...and have come to realize in the passing months that he falls in to the moderate to severe range... but it was still hard to have that in writing... it's been a rough couple of days for us..

I hope you don't mind me sharing this with you... I'm not ready to tell my family yet that we got the confirmation...but I had to share with someone who knows how it feels to see those words on paper so I can get on with the rest of the day!

I hope that you are all doing well!


Jan said...

It's a new week - how about photos of the little princess at the wedding??? Her having CdLS can't stop her being the most charming girl in the USA!

Lisa said...

The results are helpful because as you said - it allows you to progress with studies, future analysis etc.. That's good from a medical perspective that will help Hope and thousands of others.

From an emotional standpoint, it takes away that .00001% chance that you were still thinking might exist that she have the more mild form of CdLS or even something else. I know it also helps with the acceptance process.
We got a call from our geneticist about Liz's confirmation of achondroplasia while we were house-hunting. Brian took the call while I was commenting on the ceramic tile floors. He came in from the outside where he'd been on the cell phone, and I said: "She's got it, right." He said: "Yes." And, on we went examining the house - liked it but didn't get it because we worried about the location. And, the beat went on.

Hope is so lucky to have such incredible parents. You are both doing an amazing job - and she will continue to stun you and surprise you with her abilities - regardless of the official "diagnosis."

More pics. please!