Genetic Testing Explained: The Value of Genetic Tests for People with Epilepsy
In this episode of Epilepsy Explained, Dr. Elizabeth Gerard, MD, answers your questions about Genetic Testing for epilepsy. Dr. Gerard is an Associate Professor of Neurology at the Northwestern Feinberg School of Medicine and founding member of the Genetic Epilepsy in Adults Network (GEAN). In Genetic Testing Explained, Dr. Gerard answers the following questions.
This episode is generously supported by an independent educational grant from GRIN Therapeutics. CURE Epilepsy is solely responsible for the selection of the presenter and the content creation.
0:00 Intro
0:24 Why should people living with epilepsy get genetic testing done?
2:10 Which patients with epilepsy should undergo genetic testing?
3:17 What are the different types of genetic tests and which ones should
people with epilepsy have done?
6:22 How accessible is genetic testing and who do I go to for genetic tests?
7:11 Is genetic testing expensive, and does insurance cover genetic testing?
8:00 How are samples connected for genetic tests?
8:35 How long does it take to receive genetic test results and who will help me understand them?
9:37 What happens if a genetic cause for my epilepsy is / isn’t found?
Find more information at: Genetic Epilepsy in Adults Network
You can also access guidelines on genetic testing here:
• American Academy of Pediatrics (AAP): Genetic Testing for Epilepsy
https://www.aap.org/en/patient-care/epilepsy/diagnosing-pediatric-epilepsy/genetic-testing-for-epilepsy/
• American Epilepsy Society (AES): Genetic Testing in Epilepsy: Practical Considerations for Clinical Use
https://aesnet.org/clinical-care/running-your-practice/genetic-testing-epilepsy-practical-considerations-for-clinical-use
Look for new episodes of Epilepsy Explained every other month on CURE Epilepsy’s YouTube Channel and here on our website.
Episode Transcript
Why should people living with epilepsy get genetic testing done?
Dr. Elizabeth Gerard:
Genetic testing is playing an increasingly important role in offering a diagnosis to patients living with epilepsy that previously didn’t have one. It’s now actually recommended for all individuals living with unexplained epilepsy. And the reasons to consider genetic testing are many. One of the impacts that I have seen be most meaningful to patients and families is that a genetic diagnosis gives you a very specific diagnosis, whereas epilepsy is more of a syndrome caused by many different diagnoses. And giving that specific diagnosis offers often closure to the family and answers to questions like, “Why did this happen? Why did this happen to me or to my loved one?” There are other important reasons. In some cases, finding a genetic diagnosis has an immediate impact on treatment right now. So we think about things differently. We’re using the wrong drug, maybe we need to try a different medication.
Maybe this is a good idea to consider surgery, maybe it’s not. So these are some of the important considerations that genetic tests can offer immediately. And then another really rewarding thing about getting a genetic diagnosis is that I found families and individuals who get a genetic diagnosis now have a very specific syndrome, whereas epilepsy is just a broad syndrome. If we can find the name of your specific syndrome, we can connect you with people who have the same condition you do and you can learn from each other. And many genetic conditions now have family foundations and organizations that are really increasing community and connection for individuals with a diagnosis and also really pushing the field forward in terms of research.
Which patients with epilepsy should undergo genetic testing?
Dr. Elizabeth Gerard:
So genetic testing is now recommended for anyone with unexplained epilepsy. Having an epilepsy that started early in life infancy or childhood will increase the likelihood that a genetic test will give you a genetic diagnosis. Also, having neurodevelopmental differences like autism spectrum disorder or developmental delays or learning differences may also increase the chance that a genetic test will be positive. However, it’s important to note that patients of any age, even with later onsets, can still get positive genetic diagnoses from genetic testing. And also people without other learning disabilities or developmental disabilities may also have a genetic diagnosis. People who have a strong family history of other family members who have epilepsy may have a higher likelihood of having a genetic epilepsy. However, it’s really important to note that the majority of patients who are diagnosed with genetic epilepsy do not have a family member who has epilepsy.
What are the different types of genetic tests and which ones should people with epilepsy have done?
Dr. Elizabeth Gerard:
So for most patients with epilepsy who undergo genetic testing, the first recommended test nowadays will be an exome or genome. We call whole exome sequencing or whole genome sequencing. Whole exome sequencing is probably the most common in many clinics. Whole exome sequencing sequences reads through 2% of our DNA, the DNA that exists in the exons. The exons tell us the instructions for making the proteins in our body. And a common analogy is that this can be sort of like a recipe for making proteins. So these are the sort of best studied parts of our genome and most of the genetic conditions that we know well so far can be identified in genetic mutations that are found in the exome. We are increasingly using whole genome sequencing that became available to patients in the last few years commercially. And genome sequencing tells us about the information in between the exons.
So if you continue the analogy and you think about the exons that are in a recipe book or a cookbook. The genome tells you about reading through the entire cookbook and catches the parts that tell you about how to use the recipes and an instruction manual on how to use the recipes, if you will. And so the genome reads through 100% of our genetic code. So genome sequencing also tends to the new technologies that are being used for genome sequencing can give us information and pick up certain types of genetic changes that exome might miss. And so more and more we’re moving towards using genome sequencing. But whole exome or whole genome sequencing are often the first test that we do. And as you can imagine, they generate a lot of data. They have to be interpreted with expertise. And often it’s recommended that the parents of the individual undergoing testing also contribute to this test to help the interpretation in terms of vetting the variants that we find in our genetic code.
While exome and genome are generally the recommended testing now, many people will start with an epilepsy panel when starting genetic testing and this is a very reasonable approach. An epilepsy panel reads through about 200 to 500 genes depending on the panel and the company. And these are curated recipes or genes, the exomes of those genes that have been very strongly associated with epilepsy. And these epilepsy panels will be the most likely to include the genes that are likely to have a treatment impact immediately. So if you’re looking for a rapid and sometimes more affordable or covered test, a panel is a high yield test that could be done first. There are a few other genetic tests that we sometimes recommend for patients with epilepsy or unexplained epilepsy. Those can include a karyotype, a microarray, or mitochondrial testing, and those would be selected based on the workup that’s been done so far and the individual symptoms.
How accessible is genetic testing and who do I go to for genetic tests?
Dr. Elizabeth Gerard:
So fortunately, genetic testing is becoming more accessible, but we do need to continue to strive to get this more accessible and affordable for everyone and increase our investment in genetic counseling services so that everybody can have easy access to genetic testing. If you are interested in genetic testing, I would say that the first place to start is discussing it with your treating neurologist or epileptologist. They may be able to start and order some tests that would be the first-line test for genetic testing for your condition. However, they may also recommend that you see a genetic counselor or refer you to an epilepsy center with expertise in genetic testing.
Is genetic testing expensive, and does insurance cover genetic testing?
Dr. Elizabeth Gerard:
So genetic testing is becoming more affordable and insurance companies are recognizing the guidelines that it is recommended for most people with unexplained epilepsy. Having said that, insurance coverage can vary widely from state to state and by type of insurance. So it’s really important to have a good understanding about what the cost could be for your genetic testing and genetic counselors can provide that estimated cost usually and other affordable options. When genetic testing is not covered by insurance, it can range from a few hundred dollars to a few thousand dollars. Many genetic testing companies will give you an upfront estimate and many of them offer financial assistance for people who can’t afford it.
How are samples connected for genetic tests?
Dr. Elizabeth Gerard:
It’s fairly easy to submit your genetic testing sample. Samples can be run on blood tests and that might be recommended in some scenarios, but very often we can do genetic testing on a cheek swab where you run a Q-tip on the inside of your cheek or even from spit testing. And so these are kits that can be sent in the mail and you can return them. Really the more intensive part about doing a genetic test is getting appropriate counseling before you do the test.
How long does it take to receive genetic test results and who will help me understand them?
Dr. Elizabeth Gerard:
So this can vary. The genetic test results can come back as early as a few weeks to, it may take up to three months when you’re looking at larger data that needs to be analyzed. In certain settings like in infancy and in hospitals, sometimes they can offer what’s called a rapid genome. But most of the time in the outpatient setting, we’re looking at between a month to two months to get your results back, sometimes up to three. What’s really important though is that you receive those results from an informed professional, either a genetic counselor or a doctor who understands genetic testing, because the results can be quite complicated to understand. And so putting those in perspective is really important. So in our clinic, we ask to meet with everybody even if their genetic testing results are negative because we think it’s really important for that to be put in context.
What happens if a genetic cause for my epilepsy is / isn’t found?
Dr. Elizabeth Gerard:
So, if we do find a cause for your epilepsy that’s genetic, that should be shared with your treating doctors and incorporated into your medical chart. This may have an impact on your treatment or how we conceptualize your care. It may sometimes lead to further specific genetic tests that are recommended because of, I’m sorry, specific clinical tests that are recommended because of your genetic diagnosis. And even if it doesn’t have an impact on your treatment right now, knowing your genetic diagnosis can help you and your doctor review the literature periodically to see what is being learned and what treatments are being developed for your specific genetic syndrome. The other thing is if possible, your genetic specialist will connect you with opportunities to get involved with family foundations or Facebook groups where you can actually learn from other people who have the same condition that you do.
If your genetic testing comes back negative, then it’s really important to first meet with a genetic professional to see if there’s any other testing that should be done right now. It’s important to understand that if your genetic test is negative, it doesn’t mean that your epilepsy doesn’t have a genetic basis. It just means that the testing we have right now or the test we did right now couldn’t pick it up. And so we’re really recommending revisiting genetic testing now anywhere between one to two years after the original test is done. One thing that’s important to know about exome and genome is that once the sequencing has been done, the data is there. And so a re-analysis of data is simpler and can be looked at again to see if we found new information based on research that’s been done in the last year or two.
