Thursday, July 2, 2015

The Good News at Last

It has been a long road for our family, wondering what might be the root cause of Aurelia's many troubles. Now, after copious amounts of tests, and scans, and images, we know. Aurelia has been diagnosed with a rare genetic disorder called, Osteopathia Striata with Cranial Sclerosis, or OSCS.

We came to this diagnosis after having our, and Aurelia's, genomes completely sequenced. This, as you can imagine, was a pricey series of tests, and required persistent pressure on our insurance company and other creative alternatives, such as trying to find studies associated with congenital heart defects and kidneys without a genetic diagnosis.

So how did we get to this diagnosis? Well, at first we thought Aurelia might have a genetic disorder called Rubinstein-Taybi Syndrome. She had many of the physical characteristics associated with this syndrome: broad thumbs and broad first toes, some cognitive delay, poor coordination, small height and bone growth, broad nose, widely spaced eyes, etc.. When we tested for this syndrome (which we did twice), we found no associated genetic mutations. We had really no other direction to go unless we could have her, and our, entire genomes sequenced and compared.

We wanted to look for mutations between the three of us and any other genetic markers that might have resulted in so many of Aurelia's challenges. We were perplexed, to be honest, because our doctor, Dr. Elaine Zackai, is not just the director of clinical genetics at CHOP, but one of the country's leading genetic experts on children. She is essentially one of the pioneers of research in these fields, and even she was stumped.

This past Tuesday we finally got our results. Aurelia has a mutation on one X chromosome in her AMER1 gene. Essentially, a base pair is a bit messed up, with a deletion and an A base inserted where it shouldn't be found. The technical term for the mutation is heterozygous for the de novo c.1043_1044delGCinsA mutation in the AMER1 gene.

This genetic mutation is not something Jillian nor I carry, but something that was unique to either the sperm or egg that conceived her. My guess is that I ate too much paste as a kid. Seriously though, the result for Aurelia is a diagnosis of Osteopathia Striata with Cranial Stenosis. What does this mean? Well, it means, for one, that Aurelia is amazingly lucky.

While this disorder is rare, her case is particularly mild because only one of her X chromosomes carries the mutation. This is a blessing, because if both X chromosomes carried the mutation she would have a much harder life ahead of her and the outcome would be, in some ways, possibly crippling. Boys or girls who carry two mutations suffer far more than Aurelia has with the resulting problems, in some cases including increased mortality, so we are tremendously thankful with the outcome.

We were astounded to discover that nearly every issue Aurelia suffers with is directly tied to this disorder. I will list for you the many symptoms Aurelia has inherited due to this disease:

  • Shorter stature
  • Macrocephaly (a larger head - for someone so small she's in the 70% in head size)
  • Micrognathia (undersized jaw/larger tongue)
  • Facial palsy (her mild right side paralysis was originally attributed to her stroke in-utero, but now we aren't so sure)
  • Small ears
  • Conductive hearing loss
  • Hypertelorism (abnormally large distance between the eyes)
  • Broad nasal bridge
  • Cleft palate
  • Pierre Robin Sequence (smaller mouth, tongue placed further back, and a cleft palate all together)
  • Crowded teeth
  • HLHS (later corrected via amazingly lucky surgery), VSDs, (holes in the heart), aortic stenosis, her wonky mitral valve
  • Apnea
  • Tracheomalacia (her airway collapsing)
  • Intestinal malrotation with a webbed duodenum (basically your intestines are all tangled and in her case also blocked off from her stomach)
  • Reflux
  • Multicystic kidney (one kidney filled with cysts and dies off)
  • Osteopathia striata (linear striations of long bones - actual lines in her bones). We saw this in her most recent x-rays for the first time. Amazing to see. Here's an example of what this looks like.
  • Selerotic cranial base (essentially, a thicker skull at the base of the head near the neck, also visible in her latest x-rays)
  • Duplicate phalange in her left hand (essentially she has two tips to her left index finger). See an example of what I mean here
  • Spatulate distal phalanges (thick or broad ends of her fingers)
  • Nasal speech
  • Speech delay (moderate)
Pretty much the only things that she suffers from that we don't see connected to this are her malformed uterus, her thyroid problems, her pituitary gland cyst, and her Cyclical Vomiting Syndrome. Does this mean that they aren't connected to anything? Not necessarily. This genetic disorder is so rare (there isn't even a wikipedia entry - yes, it's THAT rare) that not much is known about its impacts on the body.

To help you understand how rare this is, and how hard it is to diagnose, our doctor is one of the best researchers in the country on the disorder. She's published case studies and papers on the disease, but Aurelia's presentation is mild which made it harder to see and diagnose, especially with so many prominent physical connections to Rubinstein-Taybi visible. 

The question everyone always asks is, "so is there any other treatment or cure?" Sadly, no. There is no cure, and there is no treatment. I had been hoping for a silver bullet, of course, something that we were missing, something that could be changed or done to "cure" whatever has been hurting Aurelia, but with its genetic origins understood we know no panacea exists. What is wonderful about this diagnosis, and I can't stress this enough, is that we now know what to look for, what to be aware of, and what might happen to Aurelia in the future. 

Long term the prognosis for Aurelia is wonderful. She has avoided so many of the major issues surrounding OSCS, such as seizures, mental retardation, missing bones, scoliosis, serious skull malformation, higher morbidity/mortality rates, anal stenosis, atrial defects, laryngeal web, and it goes on and on and on. To see the many things children with two affected chromosomes, see

Truly, we are so lucky to have a mild form of this prognosis discovered by one of the best genetic teams in the country. This is great news for Aurelia should she ever decide to have children, as well. If she has a child with the disorder (assuming her partner does not carry the mutation), the results will also be mild. It is even possible for her to ensure that the conceived child will not have the mutated X chromosome if she chooses to have her eggs harvested. And, of course, who knows what the medicine of the future will bring! 

So, all in all, we got great news. We are doing everything we can for Aurelia given her conditions. We have successful treatment plans in place for everything but her CVS, which is a hit or miss syndrome as it is for so many kids. The latest news on that shows us her troubles are not at all allergy related and that her digestion is perfectly normal. I wonder, and we will be looking at this from a neurological perspective, if she *is* experiencing what equates to an intestinal seizure as a result of the OSCS, as opposed to a traditional seizure or migraine, which some affected children suffer. 

Our next steps include making sure all her specialists are aware of this new diagnosis, adjusting any care plans in place, and getting Aurelia re-evaluated for neurological and cognitive impact as she approaches kindergarten. A new evaluation will give us a good benchmark to work with as she ages and we watch for any other cognitive and neurological impacts of OSCS. 

Thank you, as always, to everyone for their support and prayers. We are lucky to have you.