the unifying diagnosis

One of our cardiologists called me on Monday to let me know that results of the most recent round of genetic testing had come in. He said he wanted us to come in to meet with them later in the week (Thursday) and he gave me just a few main details: 

Iris has tested positive for a genetic mutation on the ACTA2 gene on chromosome 10. Because of the mutation she is at risk of stroke and cebrovascular abnormalities, so we should see a neurologist. Gastrointestinal problems are also related to this mutation, so they want to do an ultrasound to check for malrotation of the intestines. He also mentioned that this is very likely a "de novo" mutation, meaning that Evan and I probably don't have it. And with that, we arranged to meet on Thursday. 

I took Thursday off of work and Evan worked from home. I had already had my own echocardiogram scheduled for that morning, so it was easy to pile all the medical stuff into a single day. Evan has been very busy at work, so he was (and is) very sleep deprived. On the ride to the hospital we were able to spend a few minutes checking in with each other about what is happening and what it all means. 

I have been trying to bone up on my 8th grade cell biology and genetics knowledge before the meeting, but the cardiologists were great about avoiding complicated medical terms. We really like her cardiology team, and especially like the new cardiologist/geneticist who is involved in her care. 

Much of what we discussed at the meeting was what I expected to hear. Some of it was unexpected, though. 

• Iris has a spelling mistake known as ACTA2 r179c* and it puts her at particularly high risk of having a stroke. Of all the other cases known, they are "de novo" events, meaning that the parents of the patients did not have the same spelling mistake. The mutation is dominant, so were we to have it, we would also exhibit the same prominent symptoms.  
• This mutation affects connective tissues--specifically smooth muscle cells--in the body and basically explains all of the symptoms we've observed and also tells us that there is a potential for having gastrointestinal problems, strokes, aneurysms, and dissections. 
• The mutation causes a narrowing of the blood vessels in other parts of the body, aside from the aorta, where they commonly see dilation. 
• There is a single codon (set of three nucleobases,e.g. ACG) in which she has a single "mis-spelling." It isn't a deletion, but rather instead of having an "A" or "C", a different nucleobase appears. Dr. Chatfield couldn't remember off-hand what the substitution was, but she's going to get me the full report. The result of the mis-spelling is that an amino acid called arginine is not getting produced and instead cysteine. In other patients with this mutation, they are producing histidine, though, the doctor said the effect is the same. 
• There isn't enough information to be able to predict longevity. The doctors also reminded us that -- as we continue to do our own research -- it's the really severe cases that are discovered first. In theory there could be people out there with this mutation who haven't been diagnosed with this particular defect. However, the ones we know about are all young. Our Google searches have since shown us that the oldest known person with the r179h mutation was 31 and she died a month ago.  

So, we now begin to incorporate this into our lives. Iris shouldn't be lifting heavy weights and should never become a weight lifter. She may need to begin taking aspirin after we get the MRI results. We should encourage joy in her life and ours. 

This is all very scary news...and kind of the worst of what we could have hoped for. We had a good personal conversation with the doctors at the end of the meeting. They asked us how we were handling everything and I mentioned the idea that Evan and I talk about frequently, which is, what is the difference between a meaningful life and a long life? Or, how can we make a short life meaningful? There's a difference, of course, between talking about it and doing something about it. It's hard to know what will make a toddler's life more meaningful since she can't tell us herself...so we have to project our own ideas on to her. And play with lots of bears. 

We are probably in some stage of shock after this news, especially because she seems to be doing so well. Our everyday experience of her doesn't square with this tragic news. On the car ride home we began to process it, barely. At one point Evan said, "So this is like the universe daring us to give up. This is the universe puffing out its chest at us and saying, 'What? Whatcha gonna do now, huh?'" We laughed and then cried and continued with that train of thought. We have both been incredibly fortunate (Evan's word: lucky) for more than three decades and in spite of the universe's taunt, we remain so. Our workplaces are incredibly sensitive to our situation, and we have the time and ability to think hard about the best possible course of action. Feeling particularly emboldened, Evan even said at one point, "Well, we have to have another kid, right?"




*Note: I had originally written that the mutation was r179h. That's incorrect, since the mutation produces cysteine instead of histidine.