My grandmother has been diagnosed with behavioral variant FTD (bvFTD) and I don’t know if this runs in my family. I would like genetic testing for myself to determine if I am at risk for bvFTD. How can I get genetic testing and what should I do if I have the gene?
Concerned about Genes
It is perfectly understandable that you would be worried about your risk of developing FTD after your grandmother’s diagnosis. Although 15 to 25% of individuals with FTD may have one of the genetic mutations associated with FTD, the vast majority of individuals with FTD do not. Questions about genetics are important and often complicated due to the potential impact on all family members. Let me start off with a short genetics 101 crash course and then talk about what the genetic testing would mean for you.
DNA in your cells are organized into pieces called chromosomes. Humans have 23 pairs of chromosomes. For each pair of chromosomes, one chromosome is inherited from your father and one chromosome is inherited from your mother. If you imagine your DNA as a cookbook, then your chromosomes are a specific chapter in the cookbook and the genes are the recipes written in that chapter. In other words, each gene is a set of instructions that tells your body how to make a specific product called a protein. A change in a gene that has a negative impact on those instructions is called a mutation. Please refer to Term Box below for more detailed definitions.
What this all means for you:
There are three genes known to be responsible for the majority of the genetic cases of FTD: the MAPT (tau), GRN (progranulin), and C9orf72 genes. To find out if your grandmother’s FTD was caused by one of the genetic mutations listed above, the first step would be to have a discussion with her doctor about ordering a genetic test for her if this has not already been completed.
Our providers at Penn are also able to complete genetic testing. At the Penn FTD Center, this comes in the form of a blood test. During the course of our assessment, our staff will collect a family history to determine the likelihood that a patient’s neurodegenerative disease may be due to a genetic condition that is passed on from generation to generation. If there is no established family history of anything suspicious for FTD, corticobasal degeneration (CBD), or an affiliated disease such as amyotrophic lateral sclerosis (ALS), there is a low likelihood that your grandmother’s disease may be hereditary in nature.
Her physician may also refer your grandmother to a genetic counselor to help assess the risk of a genetic cause and to guide the family through the options for genetic testing. The psychological impact of learning about any genetic cause of a disease can be considerable, so the goal of genetic counseling is to help you understand the potential results and the significance of how it may affect you. Genetic counselors can explain how genetic conditions are inherited, help you determine your risk, and provide you with options, guidance, and referrals for resources.
If your grandmother makes the decision to move forward with a genetic test, the physician or genetic counselor will need to order the test itself.
If your grandmother’s genetic test results come back as positive, this means a genetic mutation was detected in the blood test. The risk that her siblings and children may have the same mutation is 50/50. In other words, there is a 50% chance of inheriting the same gene mutation, and a 50% chance of not inheriting the mutation. The next step would be to get her children (aka your parent) tested. In these situations, there is a structured pre-testing interview and counseling procedure to help prepare individuals for learning their results.
If someone in the family is at-risk but does not currently have symptoms and does decide to find out their status for this genetic mutation, we call this presymptomatic genetic testing. Presymptomatic genetic testing is an intensely personal decision, and it is important to fully consider the potential risks and benefits. An individual considering presymptomatic genetic testing should receive genetic counseling as well as a consultation with a mental health professional before moving forward with genetic testing. This is to help manage the psychological impact of learning this type of genetic information, which can be considerable for many individuals.
If your grandmother’s genetic test results all come back as negative, this means that there was no genetic mutation detected. There would be no specific mutation to test you and your family for, because no genetic cause of her FTD symptoms was found. Keep in mind that if there seems to be a family history of FTD or other neurodegenerative diseases, there could be a risk due to other factors that were not included in this specific genetic test. The majority of FTD occurs for reasons that are unknown and unlikely to be hereditary. There is ongoing scientific research to understand the causes of FTD, but a negative genetic test report will provide reassurance that a genetic mutation is not likely the cause.
Anna Yung, RN
For more information about the Genetics of FTD, please read the booklet Understanding the Genetics of FTD which was written by the Penn Frontotemporal Degeneration staff and published by the Association for Frontotemporal Degeneration. There are also some excellent video resources on our Center’s website at http://ftd.med.upenn.edu/secondary/media-library. You can find videos of sessions from the most recent FTD Caregiver Conference regarding bvFTD and Primary Progressive Aphasia (Murray Grossman), Non-pharmacological Interventions (Brianna Morgan), and on the Genetics of FTD Spectrum Disorders (Beth Wood).