Awww, crap.

Awww, crap.

I did it again. I read too much. I Googled one too many times. I’ve filled my brain with the worst of it again.

I have been pointedly ignoring the Google search bar lately. There is a part of me that doesn’t want to know any more about glycosylation 1g. WHhAAaattT? cry the masses! YOU don’t want to KNOW? YOU don’t want to READ and RESEARCH and KNOW!?!?

That’s right. I know what my genetic counselor and Wikipedia told me on E-Day, and that’s as far as I have taken it. My boys are dead and I know what killed them. The truth of it is that there isn’t much to read. There are 10 (now 11) recorded cases of 1g. Those cases have across-the-board anomalies. Just two (in sibs) presented heart defects. BOTH my boys had heart defects. Dandy Walker is also a mentioned presentation, but not in all cases. The problem is this: There aren’t enough of us to survey to fit into symptoms. This is a syndrome that is “syndromatic,” meaning that there is this and that problem and they all add up to something, but no one is sure what that something is until a genetic test confirms it or an exome finds it.
The only thing that is really consistent about glycosylation 1g is that all the babies died. ALL OF THEM.

So I made the decision to choose peace, to enjoy the high of diagnosis and just live in the relief. I pinned to Pinterest instead of worrying about genetics. It was a lovely vacation from being me.

Then I had to read something about it. Not so much about glycosylation, but more about recurrence. This is hard to nail down statistically for all the same reasons it is hard to stuff these poor dead babies into syndromes using birth defects. There just aren’t enough of us to know.

Of course I found something, mostly because I wouldn’t have stopped looking until I found SOMETHING.

www.ncbi.nlm.nih.gov reports:

In the autosomal recessive disorders, the theoretic risks to each sib of an affected individual are, at conception: a 25% risk of being affected, a 50% risk of being an asymptomatic carrier, and a 25% risk of being unaffected and not a carrier. However, based on outcomes of at-risk pregnancies in families with a child with PMM2-CDG (CDG-Ia), the risk of having an affected child is closer to 1/3 than to the expected 1/4.

What?

You mean to tell me that the rarest of rare diseases diagnosed with a previously undiscovered micro-deletion presents itself in an above-average recurrence than the assumed autosomal recessive theory?

Of course it does.

Now the question is: Does the 1/3 recurrence risk carry across all 19 variables of glycosylation? This study quotes 1a, which is the most common and the mildest form of glycosylation. Does it mean the same for 1g? Or again, are we too rare to know?

Damn you, Google. You win again.

Looking back, moving forward

The last two weeks have been good to me.

I woke up this morning and realized that I have not had a panic attack since E-Day. The panic used to wake me up in the middle of the night — that crushing feeling in my chest and the certainty that I wouldn’t get through the night. This feels like a milestone to me, and I haven’t had many milestones since my second son died.

Yesterday my genetic counselor called to follow up. Good news: Baylor College of Medicine will not only test my first son’s DNA in an attempt to confirm the glycosylation killed both boys, but they will do it for FREE. All I have to do is sign the paper and write a $25 check for DNA transfer.

Of course I had to ask the question no one wants to think about: WHAT IF my first son’s DNA shows no glycosylation? What then? What if that really teeny tiny deletion on my husbands half of his genetic makeup isn’t there? Then what?

“I think that is our fear,” the GC said. “But we will cross that bridge if we get to it.”

How quickly this mama’s mind jumps to genetic disaster!

I also received my summary of care from the clinic, which sort of briefs up the total visit with genetics in case I forgot anything or have any questions. These summaries are fantastic for me. I keep them and read and re-read them because they are, in a way, like the maps through this journey. They show all the dead ends we have met in “going to the wall.” This last summary shows that we reached out and touched the wall and got answers. It is the X that marks the spot.
In the summary, there is a note that my first son’s DNA (tested via microarray) clearly showed my Chromosome 22 mutation (rare, but discovered), but not my husband’s, as it was too small and completely undiscovered and not on the map of things to look for.
Now I can take some very small comfort in the fact that it is discovered now, that someone out there who may only get to the microarray testing of Chromosome 22 will have the benefit of the discovery — a benefit we did not have. If this had been discovered sooner, we would have known what happened to our first son at the microarray and had answers nearly a year earlier.
I’m here to tell you that at my advanced maternal age of 34, a year makes all the difference in the world.

So here’s to another two panic-free weeks in the Ohio sunshine (I hope). And thanks to the ladies who commented on my last post. A writer is only as lucky as the readers who read, yes?

What would you do?

One in four. One in Four. One in FOUR. Twenty-five percent. Seventy-five percent. Risk. Gamble. IVF. Recurrence. Success. Termination. CVS. High risk. Paint the nursery. Order the headstone.

The words run through my head like a news ticker. All day. All night. What should I do?

What would you do?

In the days following our big exome reveal, the shock sustained by our hearts has settled beyond the autosomal recessive recurrence risk. I’m not sure if I would say that our thoughts have extended beyond the understanding of the genetic gamble or if I would describe it as not having gotten any farther than the sheer statistics of our situation.
If I am a carrier of a very rare mutation, a ONE IN A MILLION mutation, and my husband is another one in a million (though it is more rare than that, he is the ONLY known mutation), plus the chance that we would meet and mate, and then the one in four chance of affected pregnancy - holy crap that’s a sad statistic.
And it isn’t fair. Not that any part of this journey has been fair, but come on! I never win the lottery. Heck, I never win a prize basket at the local animal shelter spaghetti dinner. I am never the one in a million. I am never the one in a thousand. Of all the things, of all the ways to be the ONE, why do we have to each be THE ONE and then be THE ONE together?
Thinking about it makes me sad and tired. It makes me irrationally, explosively angry. It brings out a new wave of fresh grief, on a new level of grieving.

Let’s break it down: One in four for any disease is the same outcome, depending on your luck. But one in four for the ultra-rare variant that no one else in the entire world must suffer is mind-bending. I don’t know where to start in untangling this knot of reasoning in my mind.

Let’s get to the action part of this situation - what do we do? Try naturally and roll the genetic dice? It was a 75 percent chance of success the last two times and that didn't happen. The genetic counselors are careful to stress that it is a one in four chance with each pregnancy regardless of the outcome of the previous pregnancy. So, yes, one in four of affected baby, but three to one for a healthy baby.

IVF/PGD? Well, let’s take out a mortgage on the house, shall we? At $15,000 to $20,000 a pop, IVF is a not so fun way to throw money at the problem. I do want to say that it is nice to have this as an option because a lot of people don’t have a diagnosis and I do, which means I have a shot at it. Some people would pay double for this shot. This is the money that puts that addition on our house. It’s the money that sends our daughter to college. It is our retirement, which I’m guessing we will need someday. Or it is IVF, which may or may not work. A lot of ladies like me have no trouble getting pregnant naturally, but then spend $20,000 on science and it fails. Heartbreaking.

Do nothing? What if - and stay with me on this one - what if we just didn’t get pregnant again? What if after all the stress and struggle and science to get the exome with diagnostic results and we just didn’t use it? What if I get a prescription for birth control instead of a referral to an endocrinologist? I don’t think I would regret this decision in the short term. Long term is a different story. I don’t want to be 37 or 39 or 42 and figure out I desperately want a baby.

So readers - are you out there? I’m breaking the third wall and asking - if you were in my very special, one-in-a-million situation, what would you do?

The rarest of the rare - a diagnosis, definitive

"We found it. We found it," our genetic counselor blurted out. "It's recessive."

And I started to cry. And then she started to cry. So we cried.

For the last 34 years I have been carrying a rare mutation on Chromosome 22, gene ALG12. My husband has spent his 32 years on this Earth carrying the only known mutation of its kind, also on gene ALG12. This causes, specifically and definitively, Congenital Disorder of Glycosylation type 1g - a rare and fatal form of a rare disease, caused by rare mutations on rarely affected genes. There are 500 known cases of glycosylation in the world. Our type - 1g - has only 10 (now 11) known cases. In all cases recorded in medical literature, not one of the babies survived.

"Literally, there is a one in a million chance you carry a mutation on this gene and then for the two of you to find each other..." the GC said.

Factor in the 25 percent chance of affected pregnancy - multiply that by two - and you have some really big numbers and some really sad statistics.

So I hold the exome data from our second son in my hand - a scant six pages of heartache and wait and worry. The printout tells the tale of a little boy who would never be born, who would never grow or play or cry, a little boy who held mutations on five other genes for four far more common autosomal recessive disorders and was a carrier for the dominant Cornelia DeLange syndrome - and the rarest thing, the thing no one in Vegas would have worried about statistically - ended his life and our dreams for him and his brother.

We spent all of yesterday trying to wrap our heads around this new information. First, I think, is the stunning realization that the exome found the cause. We had a 25 to 30 percent chance of diagnosis. Of the 30 exomes reviewed by the doctors at our hospital, ours is one of the few to offer such helpful information.
Then, out of the doctor's office and at a ironic hipster coffee shop, we wrapped our hands around mugs of warm chai and wrapped our heads around our future. The autosomal recessive 25 percent has always been our "best case scenario," though we've lost this gamble twice so far.
IVF with PGD is a possibility for us now. Cost is a huge factor, and so is the time frame. It would take weeks to begin the process and for doctors to begin the PGD probe that would find potentially skewed genes in our embryos. But, that said, I'm not sure I would be ready for a pregnancy any sooner than that, either.

I think the one thing that is most notable to me at the end of the exome is the blanket of peace that seems to be tucked around our little family now. The diagnosis in no way brings my babies back to me. It doesn't change any outcomes. But knowing what we know now, saying that we have the information, that we took this to the wall for our boys, is like balm on my still-raw heart. I have so struggled with this unknown killer - was it me? Was it my husband? How could this happen with no prior family history? My questions are answered and there is a calm in my mind and a stillness in my soul that I welcome with all my heart. This is peace. The decisions we made as new parents of lost boys were the right decisions. We have been validated in all the ways every parent hopes to be validated. No one can tell us otherwise.

This is not the end of our genetic journey, by the way. Far from it.
Baylor will now retrieve our first son's banked DNA for comparison to our second son's exome, to confirm - once and for all, that this is the gene mutation that killed both boys. This will put a diagnosis once and for all on the syndromatic physical evidence from MRI's, ultrasounds, genetic testing and autopsies on both boys.
We have been approached by the lead geneticist at our hospital, as she would like to write a medical paper - to be published in a medical journal - about our boys and our genes and our exome. We have also consented to an interview with a major metro newspaper to tell our exome story. This only furthers what I hoped to do with this blog in the first place - to shed a beam of light on the medical and very emotional journey of the exome - what it means for people, for families like mine, who never dreamed they could be so touched - and so saved - by science. I hope that the brilliant minds at Baylor College of Medicine and all the other major and minor players in the world of Sanger sequencing keep congratulating each other on the successes of the exome process, but also take a minute to remember that the results are as emotional for their patients as they are significant for science. At the end of the day, exomes are for people, not just scientists. Exomes may save lives, but they also heal souls.

Keep an eye on this blog space - I'm not done with this journey.

The long end to a long wait (2 days)

I woke up this morning feeling like the sky was going to crush me. The anxiety of the day is overwhelming. I nearly passed out in the shower - I tremble as I type.
The weekend was fine, but mostly because I was insanely busy with a family visit out of town. But back home, in my own bed, with my own laundry waiting for me in the washing machine and my job beckoning, I became crippled by my own thoughts.
Two more days.
My genetic counselor called on Friday to tell me that the Baylor lab had finished the exome and was awaiting a sign-off by the medical director there. The report will be released today or tomorrow and we meet to go over the results on Wednesday.
After 96 days of countdown, it is here. It is here. But now I have to face what comes with the “here and now.” Either we find out what killed my boys or we don’t. It is a classic situation of THIS or THAT. CUT and DRY. BLACK and WHITE.
That said, I got the “but” from my genetic counselor.
She warned me, again, that the test could come back without answers. Of course they will have found everything they can find as of now, but what the clinical significance of those findings mean could be unknown.
She also noted that the exome could uncover “other issues,” meaning that our son could have been a carrier for Cystic Fibrosis or another recessive disorder. Lots of little things that could mean a lot or nothing could rise to the surface of our genetic pool.
So I am going to spend the next two days jotting down all my questions for the genetic counselor - what does THIS mean? What does THAT mean? Can we cross-reference or target test to see if the findings in my youngest son match anything in the genetics of my oldest son?

I need strength. I need peace. I need answers.

Screw the countdown! The exome is back!

My genetic counselor just called - the exome is back! We go in for results on Wednesday! aaaauuuaaahggggahhhaaahh!




OK - seriously - new countdown -  5 days!