As discussed in my last post regarding the “Extensive Genetic Test Results”, this is the letter that was mailed to us regarding the phone conversation that I had with the genetic team. This goes into further explanation regarding what they found when they performed the WES genetic test.
May 12, 2017
Dear Ashley and Jack,
You are receiving this letter to provide more information about Jackie’s genetic test result. Jackie had a comprehensive genetic test, called whole exome sequencing (WES), which analyzed all of his genes. As you may remember, genes are like books that provide instructions for our body to work properly. We get one copy of every gene from each parent. This test was looking for misspellings and extra or missing letters in those genes. A copy of the test report can be found enclosed with this letter.
This testing did not identify a definite cause for Jackie’s medical concerns. The lab did report a genetic change of uncertain significance in one gene, MYRF, which they call a “candidate gene.” This was a genetic change that happened new in Jackie, meaning that he did not inherit this change from either of you. Currently, it is believed that this gene plays a role in how electrical impulses move through the nervous system. We do NOT believe that this change, even if problem-causing, would explain Jackie’s medical concerns.
a. A variant of uncertain significance is a genetic change that there is little to no information about because it is rare or has never been seen before. As more information is collected about human genetics, these changes are often reclassified to be disease-causing or benign.
b. A gene may be referred to as a “candidate gene” when there is little to no information known about it, and no human disease is currently associated with it. This is often the case with more recently discovered genes. The genetics lab will report changes in these types of genes when they are suspicious that it could lead to the medical issues in question, based on its function.
When WES does not identify a cause for someone’s medical concerns, it does not exclude the possibility that there is still an underlying genetic cause. We have over 20,000 genes, and we only currently understand the function of about 5,000 of them. Therefore, it is possible that more information will become available in the future that could aid the lab in identifying a problem-causing change in Jackie’s genetic information. As we discussed previously, the genetics lab offers a one-time reanalysis of an individuals genetic information at no additional cost. The lab’s policy is that this reanalysis can be requested no earlier than 1 year after the original test date. We typically recommend pursuing reanalysis 2-3 years after initial results, as this increases chances that there will be new, helpful information available. We can facilitate this reanalysis for you at your request.
Unfortunately, we cannot determine exact recurrence risk without a known genetic cause. As we previously discussed, most often when a child has significant medical concerns, and neither parent has a history of similar issues, the condition is either transmitted by autosomal recessive inheritance, or it was something that developed new in the child and was not inherited at all. Autosomal recessive means a genetic change for the same condition was inherited from mom and dad. If this is the case, there would be a 25%, or 1/4, chance that a future pregnancy would be affected. If the condition was something that happened new in Jackie, then there would be <1% chance that these specific medical concerns would happen again. Three to five percent of all babies are born with a birth defect or genetic condition. Preconception and prenatal genetic counseling are options to monitor future pregnancies for some of these risks.
The test report did include a result about one other gene that is not related to Jackie’s main medical concerns. Jackie was found to carry a change in one copy of the DHCR7 gene, which he inherited from Jack. Mutations in this gene are associated with a condition called Smith Lemli-Opitz Syndrome (SLO). In order to have SLO, an individual must carry two DHCR7 gene changes, one in each gene copy. This result tell us that Jackie and Jack are both carriers of this condition. Information about this gene was included in Jackie’s exome analysis because individuals with SLO can have some similar minor features as Jackie, such as cryptorchidism, or failure of the testes to descend. However, individuals with SLO typically have several additional physical features such as fused toes, extra fingers or toes, cleft palate, small head size, characteristic facial features, and problems with several organ systems including the cardiovascular, respitory, genitourinary, and gastrointestinal systems. People who are carriers of a genetic condition are not at risk for having symptoms of the condition, but could have a child with the condition if their partner is a carrier of the same condition. SLO carrier testing could be considered for Ashley to further clarify the risk of having a child with SLO.
If you would like to discuss this information in person, you may schedule an appointment. Please do not hesitate to contact us with any questions.
We feel blessed to have been able to care for Jackie. Please accept our deepest sympathy for your loss. Our thoughts and prayers are with you and your family.
After receiving these results the genetic team asked if I wished to have the test performed to verify if I too am a SLO carrier. I asked for pricing of the test and once that information was received I authorized the genetic team to have the SLO carrier testing to be preformed. I was told that we would have results in 4-6 weeks.
We love you Jackie!
#ourjackofhearts #chdawareness #SLOawareness