A Partial Diagnosis?
Last Wednesday was a big day for us. After 6 months of waiting, we finally received the results of Elliott's whole exome sequencing. (This is an elaborate genetic test that decodes an important portion of a person's genome.) What we learned is a mixed bag of hope and frustration, giving us some insight but not nearly as much as we'd like. Here is what we now know: SCN8A p.R850Q.
That bit of impenetrable code is the notation for a specific genetic mutation. (Disclaimer: I am a lay person, and I'm bound to get some of the biology wrong here.) The SCN8A gene is a long genetic "word" that gives instructions to the cells on how to build a particular type of protein, called a sodium channel. These proteins control how sodium passes into your brain cells. Elliott has a typo in this word: a G turned into an A in one spot.
As far as we know (because there is no published evidence), no one has researched the effect of this particular misspelling on this gene, but computer models suggest that this error would probably mangle the recipe for this protein. This in turn would cause his brain cells to get sodium at the wrong rate, either too fast or too slow -- we're not sure which. (When we talk about sodium here, we are talking about it at the cellular level, so more or less sodium in his diet would not fix this.)
In the scientific literature, there are currently only about 12 published cases of people with any change on their SCN8A gene, almost all of them published in the last couple years. (There are surely other known cases that are unpublished, and others where the person has not had the right genetic testing.) All of these published cases have different mutations within this gene -- there are many ways to misspell the same word -- and there are significant differences in the symptoms the people have experienced. That being said, several of them have some of the same symptoms as Elliott, including infantile epilepsy, developmental delays, and hypotonia (low muscle tone). This gives us some confidence that Elliott's SCN8A mutation is at least a major part of the problem, if not the only culprit.
That’s the very basic science behind what we now know. There is a chance that there are other changes on Elliott’s DNA that we haven’t found yet, and with that in mind, we anticipate additional genetic testing to decode his entire genome.
Can we call this SCN8A finding a diagnosis? When people think of a diagnosis, they usually think of something with a name, like Cystic Fibrosis or Down Syndrome. A name gives a sense of control -- a sense that what your child has is a known entity. "SCN8A p.R850Q" feels more like a serial number. It really just says what genetic change occurred and where, without any indication of what that change does or what to expect. When we tried googling this particular genetic change, we were dismayed to see this:
John Conecker, May 19, 2014
(Variations in notation gave the same result.) I’m not sure we’ve ever felt more isolated than when we saw that. To have Google come up empty on your child's condition was so scary. While we know that it is in fact likely that there are others out there with this same genetic change, it is surely extremely rare and in need of research.
The results of Elliott's genetic testing have left us feeling uncertain about what the future holds, but also excited about the possibility that we may be able to find more answers. We've made progress, but we are still in the dark as to the things that matter most to us: effective treatments and long-term prognosis for Elliott. We are hoping to find researchers who are already working on this genetic change, or -- if there are none -- to recruit some. Now, more than ever, funding research seems like our best hope.
We are very fortunate that Elliott's neurogeneticist, Dr. Vanderver, is a researcher as well as a clinician and that she has included Elliott in her research. It is only because of this that we will have access to the whole genome sequencing necessary to find or rule out other potential causes of his illness. Whole genome sequencing is currently only available to patients in a research setting, not a clinical one. We are happy that Elliott has access to this technology, but other patients with difficult to diagnose conditions deserve the same access. It is unethical for this technology to be out there and not be used to provide answers. One aspect of Dr. Vanderver's research is to prove the usefulness of whole genome sequencing in a clinical setting. This holds promise for improving the foundation for research on genetic diseases and possible future treatments.