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."