Time To Come Clean – 97 Days Post Exome

It has been 97 days since I learned the word “Glycosylation.” Still today, I say the word out loud, let it roll off my tongue and out into the air, just to be able to say it, just to be able to know it.

We have begun to heal in all the ways people heal. We have plans to bury our second son’s urn, to buy his headstone and hold a small, private service. We go to the cemetery for their birthdays and death days. I cry a lot less.

Perhaps the most significant and terrifying change in our lives has been our big, big secret for the last 16 weeks.

I am pregnant.

Now settle down! I know about one half of people who think we are NUTS to do this again, and they are right. The other half of everyone thinks we are brave and lucky, and they are right, too.

Because of all the things we have learned from our trip through the genetic experience, we have learned hope and we have learned fear. Now one emotion never comes without the other, no matter what the genetic tests say. But I must say, with all my heart and all my being, thank GOD for the genetic tests. Thank God for the definitive answers, for the black and the white with no gray in the middle. Thank God for the yes after so much no.

Our third son is heterozygous – a carrier of his father’s mutation on chromosome 22, gene ALG12.

And he is healthy.

After three ultrasounds to confirm heartbeat and growth, my husband and I high-fived during a normal NT scan with a normal NT reading. Still taking nothing for granted, I underwent a CVS with no complications. Two weeks later we got the news – the baby is genetically healthy.

Last week we went in for an early ultrasound and saw our happy baby boy wiggling and waving. So far all his major organs look good – heart, lungs, brain especially. We go in for the average anatomy scan in four weeks.

I am happy – so happy and so blessed. But I never, ever want to downplay the chance we took in the conception of this baby. We played genetic roulette and we know it. Single gene recessive was our best case scenario and it is still terrifying. A 75 percent chance of success means very little when you have failed twice. This was a life or death decision – a certain doom if genetics went badly again.

As in every turn of this journey, our decision to do this again naturally – and we very nearly went ahead with IVF/PGD – isn’t for everyone. If you are a genetic carrier and you are considering natural conception and genetic roulette, please don’t plant my story in your head as a story of success. Your chances, while statistically the same as mine, must be weighed within your own situation, within your own genetic disease.

If you had asked me last year about another baby, I would have cried my answer into your shoulder – “I don’t know.” To family, we were blunt – no more dead babies.

Though I still grieve my boys every single day, my heart is ready for the child I carry now. This baby will not bring anything lost back to me. He will not replace my lost boys nor diminish their place in my heart. But he is part of the process of healing – he is what genetics gave after so much was taken away.

He is a miracle.

Confirmative - 1g

I didn’t know how relieved I would feel.

I just got the call — our first son shares the same two mutations as our second son. The test was confirmative — both boys had congenital disorder of glycosylation 1g. My matching bookends match completely, tragically.

When I think of my boys, I think of them as individuals. I dream that our first son was blonde and fair-skinned like his sister, but imagine our youngest son with his father’s Greek complexion and dark hair. I see our oldest son as being a bit stocky, and our youngest as being a bit wiry. I think of them - my sweet oldest and my stubborn youngest - as always together. I love them both so individually, but in a “my kids” sort of lump category. I see them almost everywhere I go. I love them with all my heart.

I sit here with mixed emotions. I feel bad for my relief, but what if (WHAT IF!?) that test had been negative? What then? Another exome? Another wait? More tests, more DNA? More paperwork? My relief comes from the answers, which do nothing to bring my babies back to me. But there is something wonderful in being able to say the word “glycosylation.” To wrap my head around it. To look at it as hard evidence of a killer. To know that even if my daughter is a carrier, she will have to look long and hard across this world to find another with a mutation on the same gene.

It is relief. Sad, sad relief.

Cause and confirmation

I met with our Genetic Counselor yesterday. My first son’s genetic test to confirm glycosylation is due on Monday from Baylor.
My high risk obstetrician was in the room and she asked if there was any chance my first son’s DNA might be a mismatch to my second son’s exome.

I probably should be more concerned about this, to be honest. I don’t know what the implications on my life and sanity would be if that test came back and my first son just didn’t have congenital disorder of glycosylation 1g. What of our big “answers” then?

But looking at the big picture, I think our GC is right. This test is confirmative. Both boys had the same or very similar defects. Even without looking below the surface to the chromosomes and genes, you can see the way the brothers matched each other: The neural tube defects with a Dandy Walker variant in one, Dandy Walker in the other; the heart defects with both having ASD and VSD; the recessed jaws, the renal problems...
Of course my first son also had hand and foot deformities. My second son had a severe diaphragmatic hernia.
But when I think of my boys, I think of them as bookends — a tragic matching pair. I agree that this test is confirmative. If it exists to do anything more, it exists to prove me wrong.

The days are warm and cold here, a perfectly flawed northeast Ohio spring. It was raining through the sunshine on our drive to the Cleveland Clinic yesterday. It has been 58 days since our exome diagnosis. I kept the widget on my phone running - who knows why. It keeps my mind on my boys.

My boys. Represented in my life by my brief memories, a memorial necklace around my neck and a handful of genetics reports. On Monday I’ll get to add another to the pile, to my first son’s box of memories and momentoes. Wherever these angels of mine are, I hope they know the impact they had on this world, the difference I hope we all make to someone with the prenatal diagnosis of 1g. I will not let their legacy be as small as the micro deletion that killed them.

Exomes as prevention

There is something hiding in your DNA. There are couple of things I’d like to take issue with in my own genetic code, but alas, we have no say in the mistakes, flaws, mutations and additions to our genes.
My boys had flaws on Chromosome 22 - a result of the unfortunate genetic mash-up between their mother and father. Their chances of being affected - just 25 percent - and their chances of survival  - zero percent - shows what road maps our exomes can be.

But exomes aren’t just for affected babies and their parents. Answers can come for the healthy and living, too.

Actress Angelina Jolie made big headlines this week with the news that she underwent a radical double mastectomy because she carries a fault on gene BRCA1, which increases her risk of breast cancer and ovarian cancer. Her mother died of ovarian cancer at age 56. In her New York Times op-ed piece, Jolie notes that her chance of developing breast cancer was 87 percent. She also has a 50 percent chance of developing ovarian cancer.

“Only a fraction of breast cancers result from an inherited gene mutation. Those with a defect in BRCA1 have a 65 percent risk of getting it, on average,” she wrote.

I can’t speak for what “most women” would do if given the same odds, but I can say that a double mastectomy before a cancer diagnosis is not something I think insurance companies would eagerly cover, leaving most at-risk women to self-test at home and worry. In fact, I wrote a story for my local newspaper in 2009 about how the United States Preventive Services Task Force tossed the standard of mammograms at age 40, instead recommending women get their first mammogram at age 50.
The doctor I interviewed said he wasn’t concerned about fellow doctors supporting early cancer detection for women at age 40.
“It is the insurance companies I am worried about,” (he) said. “I am concerned insurance companies will take this study and turn it into an opportunity to decline to cover mammograms. That is the concern.”

I wrote on this blog about how expensive exomes are, but how beneficial they could be to the people who need them most but can afford them least. This is not a test run for “no reason” or because your mother died of cancer. There is a consensus among my doctors - most of them stunned that the test was covered for us - that our insurance company simply didn’t know what the exome was, that it was coded as a genetic test like all the other genetic tests we had ordered, and that they literally ‘didn’t know to deny it.’

I’m certain that Jolie, who wrote of her concern about the genetic line of cancers in her family, didn’t think twice about having the genetic testing - at an average cost of $3,000. I’m certain that if her health insurance denied a non-medical double mastectomy, she was able to fund the procedures herself.

The question is - who should decide if you get an exome? A doctor? An insurance company? You? Who should make the decision about a double mastectomy or other “elective” surgery? Should the discovery of the faulty BRCA1 gene make the decision? Will testing for that gene become as common as mammograms for prevention?

“For any woman reading this, I hope it helps you to know you have options. I want to encourage every woman, especially if you have a family history of breast or ovarian cancer, to seek out the information and medical experts who can help you through this aspect of your life, and to make your own informed choices,” Jolie wrote.

But I am skeptical that it comes down to a woman’s own “choices.” Given my own rocky experience with making my own “choices” about my health and body and children around laws and regulations written for women who make elective choices instead of necessary ones, I don’t buy it. If the state of Ohio cared about me and my situation, I would not have had to seek health care in Pennsylvania from doctors I didn’t know or trust. My experience was a nightmare plucked straight out of a horror film and it was directed by the law makers of my state.

I don’t believe they can be trusted to let women make these sort of choices about their own health. Mark my words - radical double mastectomies will go from being viewed politically as the smart choice of brave women to become the superficial choice of women who want free breast implants.

But wait! What about the blood test? What about pinpointing BRCA1 to make the determination?
I have a diagnosis on gene ALG12. If I got to week 22 of an affected pregnancy, the proof of that blood test would mean NOTHING. There is not a health care professional in Ohio that could help me.  I would pack my suitcase and go back to the chop shop in Pennsylvania. Because that would be my only “choice,” genetic finding or no genetic finding.

More people need exomes. More insurance companies need to cover exomes and the procedures they dictate after findings. This is serious science that can not only save lives, but direct us down our individual medical paths toward longer, disease-free lives. I’m not talking about just prenatal glycosylation or breast cancer — heart disease, prostate cancer, liver disease, kidney disease, Cystic Fibrosis, Alzheimer’s! Imagine if the disease that killed your grandmother could have been prevented 20 years before her diagnosis. Imagine what that would have meant for her, for your family.

For the record, I think Jolie made the right choice, but my heart hurts for the hardworking Ohio women who will never have the benefit of preventative genetic testing or the surgeries that could save their lives.

The Still Point of the Turning World

In the middle of my exome madness, in my daily blanket coverage of the internet and all things related to DNA/exome/Baylor/genetics, I stumbled across the book “The Still Point of the Turning World” by Emily Rapp.
Rapp’s 6-month-old son, Ronan, was diagnosed with Tay-Sachs, a fatal autosomal recessive disorder with no treatment and no cure. He died just before his third birthday.
The book is astounding. It reaches deep into my chest and puts words to my grief. I always feel a bit crazy in my thoughts - like I wonder why people are so afraid of me now. No one wants to talk to me, in case I should burst into tears or want to talk about something unpleasant, like grief or dead babies. Nobody wants to be the person who makes the Dead Baby Girl cry.
Rapp explains it. She writes about the Earth-shattering moment after diagnosis and the total devastation it leans on a life, on a marriage. She writes about those days of uncertainty - the what in the world are we going to do? times. She writes about the things no one can relate to until they experience it for themselves. We mothers of the dead all have the same, different story, but no one can stretch their imaginations around the horror of it all until they live it and NO ONE wants to live this.

A quotable quote from the book:

"Grief, we understood, would now hijack a part of our day for the rest of our lives, sneaking in, making the world momentarily stop, every day, forever."

One of the most interesting things about Rapp’s story is that she was prenatally tested for Tay-Sachs. Her husband is Jewish, so he was high risk for carrying one of the common mutations. Rapp decided to be tested and she was told that she was not at risk to pass on the disease (recessive = two parent carriers).
BUT (always that genetic BUT) it turns out she carries a rare, Moroccan mutation for Tay-Sachs, a mutation so rare that it didn’t show up on the prenatal screen.
The book shows a lot of Rapp’s background in academic literature. She goes on and on (and on) about her favorite classic books and how they related to how she was feeling. But that dialogue got in the way of her story, dragging it down to the point where I found myself skipping these parts in anticipation of more information about Ronan.
Rapp does discuss Ronan — his decline, the way every moment with him was heartbreaking and precious at the same time, the way it forces parents to live their lives backwards, grieving before a death while they wait for death.
But there are some missing parts that I, as a reader, found a little maddening.
A part of me wanted this book to be a roadmap of grief — a tourist’s guide to how to live when you want to die. I wanted to read about her relationship with her husband — did they disagree on treatment? Did they grieve differently? I wanted to read about how people treated her — was she the Dead Baby Girl at parties? Did she lose friends who think Tay Sachs or dead babies are contagious? Were there any insurance issues, how did they pay for everything? I understand how this experience changed her, but how did it change the world around her to a new experience? Will they try for another baby? Will they do it naturally?
The book, finished before Ronan’s death, also stubbornly omits the details of his death. In an interview with NPR, Rapp said she left that out to maintain some privacy in her situation, which I think I can understand, but who really writes a book about a dying child and they doesn’t discuss how she felt, how she coped, when he actually died?
Rapp also mentioned in the NPR interview that she would have chosen to terminate her pregnancy if a diagnosis had been made prenatally. But she doesn’t address this revelation in the book.
But maybe that is just me, looking for validation.

The book “The Still Point of the Turning World” by Emily Rapp is available at Amazon.com.

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?