Gene testing…used to be doctors tested for a specific disease or syndrome. It made finding a diagnosis difficult at best, and unless a child had very specific phenotypes, finding the correct diagnosis could take years. Today, one type of gene testing is Whole Exome Sequencing, aka WES, which checks for misspellings in the genetic code of more than 20,000 protein-coding genes in the genome. The geneticist explained it as looking for spelling errors or deletions on the pages of a book, a very large book. In order to obtain the best results, samples are taken from both parents to determine if any mutations are inherited, or occurred spontaneously, de Novo.
As a result of this testing, Wendell has been diagnosed with Dyskeratosis Congenita (DC), due to a mutation of the TERT gene. The National Organization for Rare Disorders website has this definition.
Dyskeratosis Congenita is a rare genetic form of bone marrow failure, the inability of the marrow to produce sufficient blood cells. Dyskeratosis is Latin and means the irreversible degeneration of skin tissue, and congenita means inborn. First described in the medical literature in 1906, dyskeratosis congenita was originally thought to be a skin disease that also affects the nails and the mouth. Only later in the sixties was it realized that patients with these skin changes almost always develop bone marrow failure. Thus, for the last 40 years or so, the bone marrow failure syndrome dyskeratosis congenita was diagnosed when patients presented with the triad of abnormal skin, malformation (dystrophy) of the nails, and white, thickened patches on the mucous membranes of the mouth (oral leukoplakia). The skin changes may be present before the development of bone marrow failure. Bone marrow failure is usually diagnosed by the low number of circulating blood cells including red blood cells, white blood cells, and platelets. Additional findings in patients with dyskeratosis congenita may include short stature, eye and tooth abnormalities, thin and early graying of the hair, lung (pulmonary) disease, liver disease, gut abnormalities, bone thinning (osteoporosis), infertility, learning difficulties, and delays in reaching developmental milestones. An increased incidence of leukemia and cancer has also been documented.
You can read more by clicking the link above, or from the list at the end of this post.
What does this all mean? Nothing right now. Typically, the gene mutation Wendell has presents symptoms later in life. So in the meantime, Wendell is also monitored by a dermatologist for any changes to his skin. A dentist and ENT watch for changes to the mucous membranes in his mouth (oral leukoplakia). The hematologist/oncologist looks for blood abnormalities that based on his particular gene mutation, could lead to aplastic anemia (bone marrow failure). BMF occurs when the bone marrow does not produce enough new blood cells.
January 31 (2017), DJ and I took him to Geisinger for annual bone marrow biopsy, endoscopy, and sigmoidoscopy. Results from the bone marrow biopsy indicate his cell production is low, but consistent with what the doctor expected to see based on his gene mutation and blood results. She also said the production level is the same as last year, so although low, nothing is failing at this time. The biopsies from the endoscopy and sigmoidoscopy were also normal, which means we repeat biopsies next January, and blood tests in 6 months.
Because Wendell was born with a low platelet count, I always pay attention to the test results when he has blood drawn. For several years, I have watched Wendell’s platelet count drop; I have also noticed low red blood cell counts (RBC), and corresponding high mean corpuscular value (MCV). MCV relates the size of the red blood cells, so high MCV is larger than average sized blood cells, which then drives the number of red blood cells down. I would point out these declines to his pediatrician, the geneticist, and anyone who would listen. Those phenotypes would prompt testing for different blood related syndromes, but it wasn’t until the WES testing that I finally got my answers. I always tell other parents, if you suspect something is off, keep pushing your doctor, eventually new technology will provide answers. Or, find a new doctor.
Unfortunately, the only cure for DC is a complete Bone Marrow Transplant. One doesn’t get a transplant until Bone Marrow Failure occurs, which put simply, means bone marrow fails to produce adequate red blood cells, white blood cells and platelets. But since we are not at that point in our lives, I am not going to go into all that is involved in a Bone Marrow Transplant. (Phew!)
As I said in my post Whole Exome Sequencing, it is good to have a diagnosis, for the purpose of making future plans. Since Wendell is going to be 17 next month, I have an upcoming appointment with our attorney to set up Power of Attorney and whatever else is needed to insure I maintain the ability to make decisions about his ongoing care.
There is much to learn about DC, I have found a great support group in DC Outreach. They have monthly family chats with leading physicians and researchers so parents can ask questions specific to their cases. They also established a bi-annual family retreat at Camp Sunshine in Maine, which I hope we can attend in the future.
To learn more about Dyskeratosis Congenita, here are a few good links.