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.

friday's appointment

Evan here, for a medical update.

We had a big appointment at Children's on Friday. We were a little late leaving the house to begin with, and then we discovered that Iris' car seat was broken and had to transfer all of our baggage to the other car. We weren't very late for the appointment, and we had to wait nonetheless for the team of expensive specialists to assemble. 

When they were ready for us, they called Sarah and me into a smaller computer room while Sarah's mom stayed with Iris in the exam room. They showed us the new CT scan and echo as well as the older MRI and previous echos.  

We didn't really hear anything too new, but we did get lots of great detail from them. 

Iris' original surgeon was there and he gave us his frank and detailed thoughts. His use of medical jargon was unrelenting, but since we already understood the issues we were able to follow pretty well. And we recorded the whole two hour endeavor just in case. His main points:

1. Her ascending aorta is in really bad shape and will need replacement in her life. It is currently stretched to 23mm, which is 4.5 standard deviations (almost certainly not normally distributed) larger than the average for babies her age and weight. The valve and descending aorta on either side of the dilation are normal-to-small in size.
2. The dilation in her ascending aorta is stretching the aortic valve in her heart slightly and is causing it to leak a bit. The leaking isn't bad now, but further stretching would damage the valve and might necessitate replacement with a mechanical valve, which would decrease the quality of her life substantially. He suggested we need to avoid this at high cost. This might lead to a surgical intervention (replacement of the ascending aorta), likely a temporary one, sooner rather than later.
3. It would be great (though unlikely) if this replacement can wait until she's big enough to take an adult-sized graft. Otherwise she would need to get it done twice, which he seemed to consider extremely dangerous. This consideration competes with (2) above, which might make for some difficult decisions in the future.
4. The "aortic root" is at the moment holding up well, though is stretched a bit by the dilation.
5. He is hopeful about her long-term prognosis (with these interventions). He thinks she'll be able to live a long time. He's a real downer, so this actually means something. 

Other points that were made by the group:

1. All signs seem to point to a systemic connective tissue disorder. 
2. The geneticist/cardiologist has a hunch (greater than 50% chance) that the aortopathy panel will come back with some positive results. (In 3-4 weeks.)
3. If any positive results come back, we should get ourselves tested before pursuing having another child. (We are definitely not in pursuance at the moment.)
4. Sarah and I should get our hearts looked at in an echocardiogram to see if we have any similar defects. Just as Iris' defects were all missed because she looked so healthy, we might have something similar. 

And there was a frustrating lapse in care that we uncovered:

After Iris' first surgery the surgeon told us that her aorta was surprisingly thin and unhealthy and would likely require surgery later in life. When we spoke to her cardiologists about this, they said there was nothing of the sort in the chart or surgery notes, and the surgeon couldn't recall such a thing and didn't think he would even have been able to make that determination. Sarah and I and some family and friends were all present after surgery when said it, and our memories were all pretty much in agreement on his points. We pushed the matter, but the conclusion the docs seem to have quietly reached was that we misunderstood what he said. His response to the recent findings exactly echoed his original statements to us ("thin, unhealthy aorta in need of further repair"). This frustrated us, but at least now she's being watched as closely as she should have been the whole time. To be clear, it seems to us that they were not monitoring her aorta like they should have been.

This of course reinforces the idea we've had all along that we are the ones managing and coordinating her care. No one else can take the time to process and integrate all of the thoughts and findings of these specialists, so it's up to us to understand and cross-check and ask hard questions. This is daunting, considering our lack of medical education.

Overall, the news of an impending surgery is really isn't new information for us. We expected as much. We've been processing it for a few weeks and will continue doing so. We briefly talked about the idea of getting a second opinion once the genetic results come in.

ct scan done. now we wait.

Thanks, everyone, for sending us your love & support. Iris did really well, though she hated to have the gas mask on. It was really hard to have to hold her down while they put the mask on her. I'm frustrated that I didn't insist that we do it in a different way, but now I know for next time.

Just before the anesthesia

We got to the hospital around 9am and we left Iris just after 10am. We waited for maybe an hour or so. I went to the hospital library and checked out some "parenting sick children" books, which Evan and I might read together.

We were finally allowed to see her after she had already woken up. We had made it clear that we wanted to be allowed to see her the first possible moment, but we don't feel like we were listened to at all in this regard. She was awake and the nurse had been trying to give her Pedialyte and apple juice before letting us see her. She was very scared and her throat hurt from the breathing tube that she had had inserted.

We hung out in the recovery area for a while and fed her lunch and that helped a lot. She was very groggy and needed extra oxygen since the anesthesia wasn't entirely out of her system.

Very groggy, but happy to be in a wagon.

The rest of the day went fine. She is on extra oxygen now -- a full liter -- but the anesthesiologist told us that she should be back to her normal flow tomorrow. We went on an evening walk and she kept talking about the moon. She loves the moon. 

And something really exciting happened this morning. Iris used her potty for the first time. Evan and I were so excited.

We have to wait a week to get the results of the CT scan, and who knows how long the genetic test will take. One of the doctors we'll meet with next Friday is a cardiologist/geneticist and she suggested an aortopathy panel, which tests for the other genetic mutations that would cause the weakening in the aorta that we see in Iris.

I don't know whether I hope they find something or whether I hope that the genetic tests turn out negative. I think that it makes sense to treat Iris as if she has a connective tissue disorder, even if they can't pinpoint the gene causing the trouble. The problem is that if she needs surgery again, the connective tissue disorder complicates the possible remedies. So, it would be good to know for certain that she has/doesn't have one.

ct scan plan

Iris gets her CT scan tomorrow morning. She has to have been fasting for 8 hours, so we kept her up a little later than usual tonight and gave her some extra food. Then I'll wake up at 4am and give her some formula, which she can have 6 hours before the scan. The fasting is required because she'll be sedated.

The sedation makes preparations easier in the sense that I don't have to try to explain the whole thing to Iris. The hospital does have a little model CT scanner for stuffed animals, so I imagine that we will make use of that tomorrow.

In addition to the scan of the heart, the pulmonary team wants to get some images of her lungs. She'll also have blood drawn for some genetic testing -- an aortopathy panel. And just to round it all out, they'll check to see that her kidneys are flushing the Losartan out properly. I suppose that she'll be on Losartan for the rest of her life, which is a bummer, though I'm glad such a medication exists, I suppose.

We then wait a week to get the scan results, so next Friday we'll meet with a team of cardiologists who will be able to tell us how big the bulge is in the aorta and also give us some more information on the leaking happening with the aortic valve.

In other news, today Iris officially started saying "no." It's fun to see her experimenting with new words to see how people react.

Evan and I are holding up okay. It seems like our emotional reactions to all this news comes in waves. I am much more vocal and weepy with it all, while Evan only occasionally mentions his feelings. This is true generally. We also have been so busy with the rest of life that we've had very little time to sit together and process it all. We work well together when there are decisions to be made, or if there is hard thinking to be done. Situations like this require a lot of that.  

cardiology check-up

Iris had a cardiology check up on Friday. I took the full day off work and Evan took half a day. I had been preparing Iris for the check-up with a play doctor's kit that we'd been using with Iris's bears at home. So I knew she would do great with the stethoscope. I wasn't sure about how she would do during the echocardiogram, which she hated last time. I had tried to explain what would happen several times to her. 

When we got there, she was extremely calm and let everyone do what they needed to do. She was so calm during the echo that Evan checked to see whether her oxygen was flowing. She was mesmerized by a cartoon playing in the background for most of the time, but occasionally she would say, "all done," or "up." Evan and I would then try to entertain her with something else, like the itsy bitsy spider. 

We did get some bad news. The echo showed that her aortic root is bulging and the valve is leaking a little bit. This is a new development. They can't determine the size of the bulge based on the echo so we have to do a CT scan in the next couple weeks. Because of this finding, the doctors are pretty confident that Iris has a connective tissue disorder, though we know that she doesn't have Marfan syndrome, which she was already tested for. So that means it's probably just a "not otherwise specified" expression. 

The bulge isn't an emergency situation, and next steps will be determined after the CT scan. They recommended that we start her on losartan, a blood pressure medication. We said we wanted to wait a little while to get some more information about it, and I expect that we'll start her on it in the next few weeks. Dr. Landeck thought that it was likely that there would need to be a surgical intervention at some point, just like Dr. Mitchell thought right after the surgery. 

The valve leakage is minor but should it get more severe and require a valve replacement, then it's likely that she would need a mechanical valve, which would require her to be on blood thinners for life. 

In addition to the CT scan they plan to do further genetic testing. They now are sure that insurance will cover further genetic testing, which they weren't sure of previously.

Evan is being appropriately circumspect, while I am crestfallen. None of this is coming as a surprise, really, and it's far too early to know what the implications are. There was a time when I thought that it might be smooth sailing, but that was a misguided hope. Mostly, I am trying to think about the next step, which is trying to get Iris ready for the CT scan, which will require her to have an IV so they can do an angiogram.

These are some photos of her after the check-up.

lows & highs

When I was in college my roommates and I had a weekly roommate dinner. During that time we'd share our weekly highs & lows. For this post I'll start with some lows and end on highs.

Iris seems to have had an SVT episode last night. She's on medication that is supposed to keep them from happening, but it's possible that it's not working as well since she's gotten bigger and is on the low end of the dosage. Apparently it's possible to have SVT episodes that go by totally unnoticed by parents. But in Iris's case she screams at the top of her lungs and can't stop crying for the duration of the episode. This is what happened last night around 9:30. Evan and I were both asleep and she started wailing out of nowhere. We tried some Vegel maneuvers on her, which slow the heart down. I've seen her heart rate get up in the 220 range. When she sleeps she's averaging about 100 these days and when we finally were able to get a reading on her last night she was at 170. We don't know for sure that it was an SVT episode but it seems likely, mostly because there's nothing else that we can think of to explain it.

Yesterday morning we had an appointment with genetics. Her first round of genetic testing showed no abnormalities, which is a relief. However the geneticist suggested we get additional testing to see whether Iris has some other syndromes that would change her future care. The idea is that she might be more susceptible to aneurysms. I was dismayed to hear this...I want to believe that the worst is behind us, but I have the nagging suspicion that it is not and I frequently wonder whether Evan and I will outlive our daughter.  

After we were done with the appointment, Iris and I walked [well, she sat in the stroller] across the Anschutz Medical Campus to get food at Udi's. I became very wistful when I saw all the people there taking breaks from their jobs. It's very difficult for me not to have any kind of professional life right now. Yes, I love spending time with Iris but the days can be very long and there's a constant feeling that I'm not spending enough time with her when I try to do other work.  

Something that is both a high and a low: Evan has been working really, really hard. I think I write that in almost every post. Despite the diluvial rains he managed to stain our interior doors in the garage and finished installing the kitchen cabinets. I'm grateful that he has worked so hard on the house but he has worn himself out and had to come home early on Monday to take a nap and buy himself some meat to eat. 

Now the highs.

We went to Costco this morning. That's not the high. The people in the Costco parking lot are the high. They are some of the best people in Denver. Every time I go [once a week] someone in the parking lot helps me. Today it was an older gentleman with a New York accent who said, "I'll take that cart for you. You've done enough work." Another high -- Evan and I took Iris out for breakfast this weekend. She did great and we thoroughly enjoyed our morning. Third, having a babysitter come to watch Iris is amazing. I was able to get a little work done on my dissertation and ended up going to get my hair cut. It's a bit shorter than I had wanted but it feels good to have short hair again.