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
- 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)
- 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)