searching for a diagnosis

Olivia’s Final Medical Story

July 11, 2016 7 Comments

Yesterday we shared the passing of our beloved daughter. Today, we want to share a little bit more behind her story.

On Tuesday, Olivia went for a muscle biopsy. Results from our recent advanced genetic screening found a “variant of unknown significance” in her TTN gene, which is responsible for the Titin protein in our bodies. Mutations on this gene could have easily explained her condition, since the Titin protein plays such an important role in how our muscles function. However, since the science of DNA is still developing and this specific mutation was never before seen, a biopsy was supposed to provide the physical evidence needed to confirm that mutation was the cause of her condition.

Instead, what we found was Olivia suffered from a rare form of Spinal Muscular Atrophy (SMA). SMA is actually a fairly common genetic diagnosis, but Olivia had what is called the “non-5q” variety. Non-5q refers to the fact that it’s caused by mutations outside of the common SMA-causing genes (chromosome 5, section q). This variety is very rare, hence the inability to diagnose it clinically or with our previous advanced testing. However, once they got a look at her muscle tissue, the diagnosis came in quickly.

The Wikipedia page for SMA is useful, but it doesn’t describe the non-5q branch at all. Her core team gave us this paper in Neurology which provided a helpful summary (going to work on getting a complete copy for here). In short, its prognosis is fatal and the life expectancy of infant onset is even poorer than SMA type 1.

We never confirmed if the TTN gene mutation also impacted Olivia. Her tissue sample was too atrophied by SMA to be conclusive. Also, systematically speaking, nerve firing causes muscle movement, so whether her muscles were healthy or unhealthy (from a TTN mutation) without SMA, didn’t matter much for the prognosis, because SMA affects the nerves leading from the spine to muscles. Our Titin explorations were looking at issues with the proteins forming the muscles directly, but in this case, they weren’t getting the full signals from the brain due to SMA.

Despite all this, we still have one test pending. While we know she had SMA and we know it’s non-5q, we don’t yet know what gene caused it and how/if it was inherited. To help us figure this out and also help our family planning all three of us had blood drawn on Friday for a whole exome sequence. Results will take a few months to be processed. We hope this data will also help future cases of her disease be diagnosed faster too.

In the end, while devastated with her prognosis, we were relieved to have a concrete diagnosis. Her case riddled so many medical professionals and labs that we worried we might be forever stuck with unanswered questions. As Dr. P said to us, her final gift to us was to let us know what she needed. She did that and she’s still a pink zebra.

Stories from Mom

Pink Zebras

July 1, 2016 13 Comments

There’s a saying in medicine, that goes something like “When you hear hoofbeats, think of horses not zebras.” If you’re unfamiliar with the aphorism, as both Luke and I were before Olivia was born, Google it later. For now, just stick with me.

See, in the world of medicine and diagnoses, there are horses. And then there are zebras. There are the more common, obvious diagnoses. (Those are the horses.) And then there are the zebras: the unexpected, the uncommon, the rare. The saying itself is actually directed towards medical professionals, and it has to do with the process (and risks) of reaching a diagnosis, but that’s not the point right now.

The point is that there are some conditions that are common, and some that are rare.

In Olivia’s case, it’s like we’re searching for a zebra on the streets of Western New York. For two months, she stumped the hospital’s top geneticist and top pediatric neuromuscular specialist. Time and time again they would visit her room, assess her, pick up on physical anomalies and point out new “clues”, but left telling us that she didn’t seem to fit the mold of any one particular disorder. And these people are no slouches! These are the specialists whose colleagues describe as “the encyclopedia of genetics”. Another team member described one by saying, “he’s the kind of guru who can diagnosis a child with a very rare disorder while still standing in the doorway, before he even walks into their room. Literally.”

To stump the best of the best is quiet impressive, little girl.

The gene sequencing seems to have confirmed it. Olivia’s symptoms are all relatively common when compared to some families of neuromuscular disorders. Muscle weakness, respiratory complications, the facial features… But the specific gene mutation identified in the test has never before been described. Never.

Olivia Grace, meeting you is more special, more unique, more truly one-of-a-kind than encountering a zebra on the streets of Rochester.

All of this is particularly intriguing to me. Intriguing, and ironic, and magical all at the same time. Because of this piece of art above. I began looking for inspiration for Olivia’s nursery in December. I originally wanted something classic with a splash of sass. I didn’t want the room to be filled with anything overtly girly, or baby like. I wanted the room to fit in with the rest of our house, and for those of you who have never seen our house: there is not one ounce of pink. Well, the direction of her nursery took a drastic turn. It is absolutely overtly girly, and filled with things that scream “nursery”. It is so clearly a baby’s room, and there is far too much pink, and most items will be outgrown, but oh well. I went there and I kind of love it so it is what it is. Baby girls will do that to you, I guess.

Back to the intriguing, the ironic, the magical part.

The photograph above was the start of my vision for Olivia’s nursery. It’s called Hot Pink Zebras by Gray Malin and it was the first item that I pinned on my secret Pinterest board for inspiration. I had planned on buying it and hanging it nicely centered over Olivia’s crib, and it was meant to be the starting point of her nursery… the focal point of her entire room.

Pink zebras strutting across a field.

I fell in love with this photograph, because I didn’t want to fill my daughter’s room with princesses and pink hearts and butterflies. I didn’t want to cast any stereotypes or expectations on her. Instead, I wanted to tell her she could go anywhere, do anything, be anything she wants to be in this world. That she should feel no boundaries, no limits in the world. That her life, her world could be as big and interesting and unique as she could dream up. I wanted to tell her that anything was possible, even being a pink zebra.

Well, I didn’t buy the photograph. Turns out that poster sized photographs by Gray Malin are expensive. But I didn’t let go of the idea of pink zebras. A pink zebra is still a focal point in her nursery.

And now here we are, searching for answers – that in the world of horses and zebras, are most definitely of the zebra type. When days are hard and my head is filled with sadness and my heart is overcome with grief, I like to think about the idea of pink zebras. I love thinking about Olivia as a one-of-a-kind gal. And I tell myself it’s almost as if I knew just how special Olivia was going to be, even before she was born.

Daily Rounds

61 Days Old: Genetic Test Results

June 23, 2016 12 Comments

First a little update, then a big one.

To start, the little lady packed on the pounds over night, and is now officially a 7 pounder. Her overnight weight was 3,230g (7.12lbs) which is just about 2 lbs up from her birth weight. She’s still way, way low on the growth chart, but any growth is good growth for us.

For the big update: earlier this week MNG Labs completed the Next-Generation sequencing that we ordered in May. We met with Olivia’s core team, along with the pediatric neuromuscular specialists on Tuesday to discuss the results.

Unfortunately, despite sequencing nearly 200 genes that are most commonly associated with known neuromuscular disorders, the panel came back “indeterminate”. In other words: the test did not provide us with an official diagnosis, and we are still unable to associate a name… a specific disorder… something well known and understood… to Olivia’s condition.

The panel did however identify mutations on two of the analyzed genes.

One mutation is being disregarded as benign, as it’s on a gene that isn’t responsible for anything that fits within Olivia’s clinical picture.
The other mutation is of much more interest to us and her team, because this specific gene is understood to be closely related to an important part of muscle function (Olivia’s primary issue).

This mutation is incredibly rare, in fact never seen before, so it is considered a “variant of unknown significance”. But… based on: the gene’s role in muscle function, the type of mutation (“likely pathogenic”), and Olivia’s clinical picture… it’s seemingly significant.

In order to more confidently confirm that Olivia’s myopothy is in fact a result of this gene mutation, she’ll undergo a muscle biopsy. A muscle biopsy is a relatively small procedure in the realm of pediatric surgeries, but it is still a surgery. Under a microscope, muscles affected by various myopathies have fairly distinct appearances, and depending on whether something atypical is observed in her muscle sample, Olivia’s team may be able to officially connect the dots between this mutation and how it’s impacting her muscles.

If they are able to connect the dots, Dr. C (the pediatric neuromuscular specialist we’ve been working with here at University of Rochester) will have the data points she needs to begin consulting with other specialists in the field with more of an expertise on this particular gene. One doctor in particular works out of NIH, and has dedicated his career to studying this one, specific gene!

Over the next couple of weeks as Olivia’s biopsy takes place and we learn more about what these test results mean for her, we’ll keep you all up to date. In the meantime, here’s today’s installment of: a snoozy, sprawled out baby.