Tay-Sachs and BRCA Testing on the Same Day?
“Can you also test me for BRCA while I am here already?” asked my 21 year old patient. He was in my office about a month before he was planning on proposing to his girlfriend. He came because he knew his sister was an FD carrier and he wanted to get screened for this condition as well as others that are common in Ashkenazim, since if both he and his partner were found to be carriers of the same disease, they would have a high risk of having an affected child (25% with each pregnancy).
I had just finished counseling him about the diseases we would be testing him for and the reproductive options for carrier couples, when he glanced at the BRCAcommunity study brochure that was lying on my desk. The cover reads: BRCA testing is right for some…Is it right for you? That was when he asked his question that many others also have asked since. “Can you also test me for BRCA while I am here already?”
Testing for BRCA is not like testing for Tay-Sachs, but I understand why the question was asked. (Note: for the remainder of this blog, I will use Tay-Sachs as the example of preconception testing, but testing is recommended for a much larger panel of diseases). We talk about how certain genetic conditions are more common in Ashkenazim. We talk about Tay-Sachs disease and BRCA-related Hereditary Breast and Ovarian Cancer (HBOC) syndrome as examples of this all the time. And we advocate for genetic testing before contemplating a pregnancy, so why not kill two birds with one stone and do it all at once?
The answer is complex and related to the differences in the conditions themselves. The first difference has to do with the nature of the diseases; that is, Tay-Sachs and the other common diseases for which we test preconception are diseases that occur in infants or young children. Some of the diseases on our panel end in early death and others progress throughout one’s lifetime, but they are all chronic diseases that burden the affected individual for the long-run. HBOC is in a different league since it is adult-onset. We don’t see BRCA-related cancers in infants or young children.
Furthermore, if a child has inherited both non working copies of the genes that cause Tay-Sachs, that child will have Tay-Sachs. However, if someone has inherited a genetic mutation in BRCA that causes HBOC, that person is at increased risk to develop a related cancer, but it is not a guarantee.
The reason we recommend carrier screening for Tay-Sachs and diseases in that category is so that couples could be made aware of their risks to have a child with a debilitating disease before they conceive or early in a pregnancy, and may make reproductive and life decisions based on their risks. Does information about adult-onset diseases—that are not even guaranteed to happen—fall into the ‘want to know before contemplating a pregnancy’ bucket?
The second difference between Tay-Sachs and HBOC has to do with inheritance patterns. Tay-Sachs is transmitted in an autosomal recessive manner; that is, carriers are not at risk of developing the disease themselves, but their offspring are at risk if both parents are carriers. HBOC is an autosomal dominant syndrome, which means that if someone carries the mutation, he or she is at increased risk to develop the disease (not just the offspring). In addition, each of his or her kids have a 50% chance of inheriting the mutation and its associated cancer risks—regardless of the other parent’s carrier status. When going to learn about your potential children’s health in a preconception genetics appointment, would you also be ready to learn about your own health risks?
My two points about the differences between Tay-Sachs and HBOC are pretty strong, and because of them, I do not know of any reproductive genetics practices offering BRCA testing in the preconception realm. The one argument that supports preconception BRCA testing is that if a couple knew that one of its members carries a mutation, this couple might consider doing pre-implantation genetic diagnosis (PGD) to select against BRCA-mutation carrying embryos when planning their families.
So while PGD is an option for BRCA carriers, we generally do not offer preconception screening for BRCA to all those of Ashkenazi descent (an exception could be someone who has a known mutation in a close family member, or someone with a strong family history of cancer). The counseling for BRCA is very different than it is for Tay-Sachs, and genetics professionals do not believe that a session about preconception carrier testing is the appropriate environment to bring it up. I wonder if our patients would agree.