Pontocerebellar hypoplasia type 6

In the days (and weeks, and months) leading up to our genetics follow-up, I was nervous. Nervous they would find something . . . nervous they wouldn’t find something. And I had plenty of time to let my mind wander to the worst possibilities, since our follow-up was scheduled for mid-February and our blood was drawn in November. Even so, being that I’m not a geneticist, my wandering mind never wound up in the right place.

“We think we found something.” Dr. Bassetti, the pediatric geneticist at Cornell handed us each a thin packet. Upon first glance, there were a lot of things in it that held no meaning for me. A lot of medical jargon and numbers I didn’t understand. What Dr. B ended up telling us would take a long time to sink in completely. Upon writing this, I think it has finally sunk.

If you’re like me and remember very little from biology class, let me first give you a brief (and very elementary) refresher on genetics. When babies are made, they get one copy of every gene from their mom and one from their dad, so (barring any deletions) everyone has two copies of each gene. Remember the big square divided into four smaller squares, with the capital “A” and lowercase “a,” and capital “B” and lowercase “b,” to show dominant and recessive genes? That’s how you can tell a child’s odds of having certain characteristics, based on their parents’ features. This is how we knew that J had a roughly 50/50 chance of having blue or brown eyes (lucky girl has the most gorgeous, bluest-of-blue eyes).

We did not know, however, that T and I each have one copy of the same gene that is messed up, giving J a 25% chance of inheriting both of the messed up genes for a pair, which she did. The RARS2 gene. This causes a condition known as Pontocerebellar hypoplasia type 6.

There are somewhere between 6 and 10 types of Pontocerebellar hypoplasia (I’ve read it both ways) but there is very little information out there about any of them. The most recent study on PCH6 that I have read stated that there have only been 27 documented cases, in 14 families. I suppose J would make 28.

So, what are the characteristics of PCH6? Children with PCH6 are commonly afflicted with early-onset seizure disorders (like Infantile Spasms), severe developmental delays, and a slew of other problems, including ongoing seizure disorders--which reinforces our concern that J is at risk for developing other kinds of epilepsy.

“Pontocerebellar hypoplasia” describes the atrophy or malformation of cerebellum, cerebral cortex, or brain stem, which can lead to microcephaly (small head--now a buzzword due to the recent Zika outbreak). The life expectancy of a child with this condition is yet unknown because so few cases have been reported and most of them have been reported recently, meaning the children are still young. One article I read suggested that there have been no reports of people with PCH living beyond their 20s, but that is more likely to be because the kind of genetic testing required to diagnose this disease is fairly new (and becoming more accessible), and most children who undergo such rigorous testing for a diagnosis are severely affected. High-functioning children like J may not be diagnosed.

Developmentally speaking, PCH6 does not seem to be a “progressive” disease, meaning at this point J will likely not lose milestones. However, microcephaly--caused when the brain stops growing, or atrophies--can set in any time in early childhood. Although J’s head size has always been within the normal range, and actually on the larger size, it’s something we’ll have to monitor closely for the next few years. Unfortunately, even if we catch it, there isn’t anything we’ll be able to do about it.

Of course, any child with a condition affecting neurodevelopment is at risk for learning disabilities, autism, behavioral problems, and (already seen in J) developmental delays.

J is thus far missing the key features that are typically seen in a PCH6 diagnosis. Her genetic test actually reported an “uncertain” result rather than a “positive” result for this reason. Back in the summer when she had her MRI, there were no abnormalities seen, which is atypical for a PCH6 diagnosis. The next step will be to have a neuro-radiologist review J’s MRI scans from last summer, and then do another MRI 6 months from now.

What will this mean for J long term? Well, we don’t know. J is doing so much better at one year of age than any other child yet known to have this condition (that I’ve read about), and since so little is known about the way it progresses, just as before, it’ll be years before we really know what J’s outcome will be.

I have had a lot of trouble digesting this information. At the geneticist’s office, this condition didn’t sound so bad, but I didn’t realize then that, even though J is doing okay right now, things could still go south. On the other hand, Dr. Bassetti did warn us that the literature available on this disease is not very family-friendly and primarily describes the worst cases, which I have found to be true.

I am relieved at having an answer, if just to know that this wasn’t caused by something I did wrong. We couldn’t have prevented this or even known that it was a possibility. But I’m terrified that J’s progress is going to halt, that she’s going to develop acquired microcephaly, or intractable seizures. She’s doing so well and I was starting to feel really hopeful about her future, but now I feel it may be irresponsible to be too hopeful. As a parent, that feels awful.

I’m disappointed that we still don’t know what to expect. We still have to wait and see how things go. I want to be proactive about treatment, but you can’t treat what you don’t yet understand, and in reality there is no treatment or cure for PCH6, only supportive options.

The other cruel part of this is that any subsequent children of ours will have a 25% chance of inheriting PCH6. This is particularly devastating to me because I was so looking forward to having another child. Now I have to consider if the risk is really worth the potential pain, not only for me and our family, but, more importantly, the hypothetical baby. There are other options. . . . Should we spring for IVF, which can be very expensive and unsuccessful, but would guarantee a child without this condition? Or should we adopt, which is also very expensive and does not guarantee a child without a significant disease or disorder? What was once just a matter of determining when the time was right, is now a huge, overwhelming, potentially financially draining, potentially heartbreaking, decision. Genetic testing can be performed via CVS at 10 weeks gestation, so we would know well ahead of the birth if our child had PCH6, but we would have no way of predicting what that would mean for that child, since it affects every child differently (I read one article that discussed two PCH6-positive neonates that died within days and weeks of birth, and another about a child who was 15 at the time of writing), and then we would be faced with the decision of terminating or continuing, something we almost had to consider during my pregnancy with J when we learned the Down Syndrome risk for that pregnancy was 1/11 (usually 1/300 or better for a mother my age). It was an incredibly difficult thing to think about. Even at 13 weeks, we were very attached to our little fetus.

The silver lining of all of this is that J can now contribute to research on a disease that is not well understood. We have the opportunity to help other families dealing with this condition, help improve access to screenings, or find treatment, and, if J continues to do well, help to give people hope.

The other thing to keep in mind is that, while there is so little known about this disease, few diagnosed cases, and J’s future is uncertain, not only does that mean that things could take a turn for the worse, but they could also continue to improve. There is nothing really to say at this time that J won’t continue on this positive track. I’m grateful that she is in the care of some very bright and attentive doctors. If it weren’t for Dr. Bassetti, we may never have known that J had this. Another doctor may never have gone to the trouble of ordering whole exome testing.

Another positive is that nothing was found in the secondary results for any of the three of us, which means that we have no genetic predisposition for developing other common diseases.

At this time my anxiety around J’s health has rekindled. I’ve fallen into my old habits of checking on her several times after she’s gone to bed in the evening and waking up at night to make sure she’s breathing. Just after our appointment J got the flu and had a fever for several days which compounded my anxiety (fevers can increase the risk of seizures). That, thankfully, has abated and she’s feeling much better.

Although I am feeling less hopeful for a good outcome right now, I am open to the notion that this hopelessness may pass, and I am determined not to let this affect how I treat J. She isn’t a different person because of this, and for all intents and purposes, we don’t know any more about her future now than we ever have. We will trudge on with her therapies and work diligently with her to improve her motor skills and social skills. J is happy as could be. She smiles all the time, and laughs, and seeks us out for attention, and shows excitement when we come home. Our day-to-day life is good and pretty much like any other family’s, and that’s what we need to focus on to get us through this!

This post features information Pontocerebellar hypoplasia type 6 and reflects my personal understanding of what I have discussed with our doctors and read in medical journals. If your child has been diagnosed with PCH6, please discuss prognosis and symptoms with your doctors. I also encourage you to conduct your own research. Your doctors should be able to provide you with up-to-date, professionally written articles.