When No Diagnosis Fits (Yet)

I will say, too, that this experience of having an undiagnosed disease has really opened my eyes to kind of the desperate spot that patients tend to feel when they don't have a diagnosis, or they don't have a treatment option for their condition. 
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Western medicine doesn't do a great job at treating conditions that have no diagnosis. We're great at, you know, once we identify the diagnosis, check the box and now we have all this, all this information about what the best way to treat that diagnosis is. But when your symptoms don't fit any particular diagnosis, I found that we don't do a great job at really thinking in a complex way about, “Well, what is the underlying cause of this symptom or this disease?” If it doesn't, you know, if it doesn't check this box, then we just aren't as good at identifying the underlying cause of symptoms that don't have a diagnosis.

DNA is the instructions for how our bodies should grow, develop, and function properly. Our DNA codes for multiple different traits including eye color, how tall we might be, how we process certain foods, or even what clinical symptoms we may have. DNA is made-up of four letters. Changes in these DNA letters are referred to as variants or mutations. Genetic testing is a process that looks at our DNA for any of these changes or variants that might be causing symptoms in an individual.  
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There are a wide variety of genetic tests that are available to patients. Commonly, patients that are undiagnosed will undergo whole exome sequencing. Exome refers to the part of the DNA that makes up our genes, and therefore whole exome sequencing is a very comprehensive test since it looks at all of our genes for any variants that might be causing the symptoms. And although only 1 to 2% of our DNA actually codes for those genes or makes up our exome, that is the portion of our DNA that we know the most about, and therefore we're better able to interpret how those variants might be causing disease in our exome. There are a wide variety of other tests that undiagnosed patients might undergo, including a microarray, which looks for pieces missing or pieces extra of DNA referred to as deletions or duplications. Or patients might undergo a gene panel in which a select set of genes are looked at that are related to a particular symptom. For example, there's a seizure panel, or there's a cancer panel, or there's a heart defects panel where they're looking at just those genes that are related to those symptoms specifically.  
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Individuals in our undiagnosed disease research study are offered whole genome sequencing. This testing is more robust as it looks at all of the letters in our DNA and not just those letters that make up our gene. This test therefore can detect variants that might have been missed by whole exome sequencing, including variants that may fall outside of our genes or when there are rearrangements to those letters in our DNA. However, less is known about these variants and therefore why this test is commonly run on a research basis in places like our Undiagnosed Disease Program Clinic. The field of genetics is advancing very rapidly and every day we're getting new insights into genetic testing and the relationship between variants and disease, and this allows for more and more undiagnosed patients to be diagnosed. 

Yeah they sent us over to the hospital because we were at the [clinic] center, and then they sent us to the Children's hospital to do the blood work after the appointment. And then it was months of waiting. And for the first, I think one or two times they did genetic testing they didn't find anything. Nothing conclusive. They said that a lot of her genes were different or mutated, but nothing that they had a name for, and they didn't know enough about those genes yet.

And so he did a test and we were really confident then that that was going to be the answer. And again, it came back with no findings. And then we did like the whole exome sequencing, and that had nothing. The infantile epilepsy panel resulted in, I think there was a slight change on the TSC 2 gene, so the gene that's responsible for tuberous sclerosis. I also have that gene mutation or change, and I don't have tuberous sclerosis. So, they said, “Nope, that's not it”. And so just, you know, again more questions than answers as we went along. And yeah, that was the first 3 years. A lot happening in the first 3 years and then, you know, things just kind of got quiet for a while.   

It is somewhat ruled out. It is ruled out because my father doesn't have that right. So that mutation can't really explain the symptoms that my father, his father, had. And because they are the same constellation of symptoms that don't belong together in any other disease state, I can't really think that the original mutation that was identified is causing my symptoms. But you know, it's just coincidence that my father and grandfather have the same issues. But certainly the mutation that was found was on a gene that is related to what causes [rare syndrome], which is a rare disease as well. And so, I certainly followed, you know, the research going on with [rare] Syndrome and the, you know, the clinical trials that are happening to see if there's any benefit for [rare syndrome]. I even reached out to a national specialist [for rare syndrome] to explain my situation, this mutation, and that my father didn't have it. And did he think that there, you know, maybe my father's results could be wrong. And he responded very, very kindly, but said, “You know I wouldn't even think that mutation that was found for myself would explain." Apparently it's a mutation that is not particularly uncommon, it’s seen somewhat regularly. And it's not usually symptom causing, even though it's on that same location as what causes [rare syndrome]. But then, especially because my father didn't test positive for that, it just doesn't make any sense. Which I knew, I just wanted someone to tell me that somehow there was an error, and this must make, you know, must be related [to rare syndrome]. And I think I'm finally at a place where I can accept that must be coincidence that, you know. I have a mutation at a spot that's related to a disease that actually has a decent amount of overlap with my symptoms. But that's not the answer somehow.   

So, I just felt like having that clinical diagnosis was very comforting and gave us kind of jumping point. Like we could just work with that, and we could follow a lot of their advice. And even like the therapies, everything, the medications for the seizures, I mean, certain medications were recommended by parents just saying like this one did not work for our kids at all, this one works, you know, tends to work really well on seizures of kids with [rare] syndrome and just kind of going through that whole thing was really helpful. 
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I mean, yeah, he definitely fits in here, but also some of the facial features he's developing as he's getting older I do see more [of the rare condition]. Like the eyebrows. He's got different eyebrows. They're definitely showing more as he's getting older. They're getting a little darker. Both of our kids have very light eyebrows. They get it from me. Can't see them on your face without darkening them. But his are getting darker with age. So now you can really see how bushy they are in the fronts here. I also notice, I don't even notice it on a day to day with him, but when I see pictures like over this weekend, when the caregivers were sending - we were sending pictures back and forth. And his nose looks different. He has a different look to his face and I almost, I feel bad like saying that as his mom, he's very handsome, he's adorable. But I do see a difference in his features that I guess I don't always notice, because I'm with him all the time. But seeing a picture when we were away this weekend, I think my husband noticed it, too, because he kind of went like his face was like “hmm like he looked kind of different” and a lot of, I don't see those same characteristics.

Again, I think because she's not diagnosed, I think nobody knows where to stick us. I mean, we have the vision portion so we've been hooked up with vision services, but she doesn't really fit in that box. And, you know, even some of the groups that we've kind of been - I don't mean - hesitate to say, because I don't know that "connected with" is the right word because it's been a lot less intentional than that. So, I mean, the only groups I think that we've really been sort of pointed towards have been ones that are vision specific and that's just such a different experience right now. I mean, in fact, the older she gets the more that I feel like vision, her blindness, is kind of a secondary. It's not sort of the primary, you know, what would you say, special need or challenge for her? I think it is there, but I think that neurological stuff is more and so it's made finding a place to fit sort of challenging because I don't know what to say. Even when I talk to people, I don't know, it has a lot of challenges that I don't even, it's hard to even sum up because there isn't some neat little. “Oh, she has this”. 

I have seen several specialists for, you know, different symptoms. But I think it's challenging. I am sure this is challenging for anyone with an undiagnosed disease but I feel like a lot of times, the medical professionals, they mean well but they don't really know what to do with you when you don't have a diagnosis. You don't fit the mold. Your issue, your symptoms sound familiar but they aren't necessarily caused by the traditional, you know, causes or issues that may cause those symptoms. And so, the traditional medicines or interventions aren't as effective. I guess I felt like they were trying to sort of fit a square peg in a round hole, sort of a thing. And I really haven't found particular interventions helpful other than just, you know, things like enlarging font sizes and things like that to just help with low vision. But unfortunately, no, I haven't found any intervention that I feel confident is slowing any of the neurologic decline.

And if you know anything about [rare] syndrome, right, failure to thrive, floppy at birth. And then a switch flips around 8, sometimes earlier and [Name's] 9.  And then they're in hyperphagia, and they always want to eat, and they're stealing food. Not there. He could care less. “When's my meal? Okay? Sounds good.” But he's always been super tall. He's always been really a social kid. He has some other features, and I don't know what they are. So our endo [in location] was like, you know, “I think he has something else going on.” So, we did, like, the genome sequencing, exome sequencing. I don't know which one it's called. Well, we did [rare] syndrome first, I believe. And so, we saw geneticists in [location] and he just had no idea. And then we also then saw a couple geneticists in [location], and you know, did the whole [rare syndrome] panel. No, but that's not it. But they're like, “We agree. There's something definitely else going on here. He just doesn't fit the [rare syndrome] mold.” Obviously, the genetics test says he has [rare syndrome], but, like, there's just other things that aren't right. Or you know, just not going there. And hey, who knows? Maybe it's a good thing. Maybe it's a bad thing, I'm like, “Well, let's figure this out.” 

And so, I said before, sometimes I feel like a fraud in the [rare disease] community because yeah he fits in here, but at the same time I feel like deep down I know that it's not [rare syndrome]. I felt like it was and then, as time goes on I feel like it isn't. But we're still gaining, and we're still giving with the community that it makes sense to stay there, for now. I mean and we've made friends, you know. We care about the community, we care about those kids, too. Our hearts are still very much there, but I don't think in the end that will be the answer. 

And that was about the time where we were starting to really transition from it might not be [rare disease] syndrome, and like, I let the mom from [location] know, like, “Hey, we're gonna explore this path. I need to step away.” And she's like, “That's that's totally fine. I understand you've tried everything to get that [rare disease] diagnosis. If there's something else out there, you need to explore it.” 
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It's a little sad, I'll say that. We found a community that we thought we were part of, and we thought for sure we were gonna get all our answers from, and the potential of not being a part of it hurts a little bit. 
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Until we find something else she will have [rare disease]. We’ll still advocate through our school district. That for [rare disease], we will still do our volleyball nights for [rare disease] until something else comes up.   
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The way her brain is wired and her understanding of the world is very black and white, and she understands that she has [rare disease]. She doesn't understand that we're also looking at other things. And I'm not gonna take away her community unless there's another one to join.   

I guess for me, I would love to be able to talk with others who had similar symptoms and to kind of commiserate about, you know, how they are managing certain symptoms. What they found to be helpful? Things like that. But because all support groups are really, you know, for specific disease states. Like, for example, my condition has some overlap with multiple sclerosis symptoms, but I don't have multiple sclerosis. And so, I feel like I can't. It's tempting to like, join a multiple sclerosis support group. But I don't have that, right? And so, it feels wrong to participate in something when you don't, you know, you don't have that diagnosis, even though there is some overlap and symptomatology. Or again, this [rare syndrome]. There's some significant overlap there, but I don't have [rare syndrome]. And so, I feel like I just it feels wrong to try to be part of a community that's really for a disease state that I don't have, even though there is probably some common ground in some of their experiences of dealing with those symptoms of their disease.