Genetic testing has long been seen by medical professionals (doctors, insurance providers, etc.) as necessary only for pediatric epilepsy patients. Despite physician reticence to prescribe genetic testing for adults with epilepsy and access challenges, it is becoming increasingly apparent that genetic testing in certain adult epilepsy patients can be beneficial.

In our last webinar, viewers learned that genetic testing can shorten a patient’s diagnostic odyssey, help tailor specific treatment options to their type of epilepsy, and aid in family risk and planning decisions. Many of these benefits also are relevant to adults with epilepsy including those who developed epilepsy as children but at a time when genetic testing wasn’t as widely available. After viewing this webinar, attendees should be able to:

1. Identify adult epilepsy patients who would benefit from clinical genetic testing.
2. Understand the types of clinical genetic tests available and how to interpret them.
3. Distinguish between clinical and research genetic testing and the value of being involved in research studies.

In addition to the information above, attendees will also hear from a person living with epilepsy who underwent genetic testing as an adult to learn more about their motivation, experience, and how it was beneficial to their overall health and well-being. This webinar is the second part of a two-part series in March that reflects CURE Epilepsy’s ongoing focus on epilepsy genetics and research on rare epilepsies. Attendees will receive a link to view part one in an email to follow this webinar.

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About the Speakers:

Gemma Carvill, PhD is an Assistant Professor in the Department of Neurology at Northwestern University in Chicago, IL. Her lab uses genomic technologies, machine learning and high-throughput functional assays to define the molecular basis of epilepsy, including coding and non-coding genetic variants. Her group also uses patient-derived stem cell models to study how rare variants in genes involved in epigenetic mechanisms cause epilepsy. Dr. Carvill co-directs the Adult Epilepsy Genetics Program at Northwestern Medicine with the goal of expanding neurogenetics research and facilitating genetic diagnoses for patients. She also works with colleagues in South Africa to develop strategies for increasing access to genetic testing, and building genetic epilepsy research in sub-Saharan Africa, to ensure that precision therapies benefit all individuals affected by epilepsy.

Elizabeth Gerard, MD is an Associate Professor in the Department of Neurology at Northwestern University in Chicago, IL.  She is an adult epileptologist with clinical and research interests in the care of women with epilepsy and genetic diagnosis in adult patients with epilepsy.  She also directs the Women with Epilepsy Program at Northwestern Medicine as well as the Adult Epilepsy Genetics Clinic.  Her research interests include gene discovery and variant interpretation in adult patients with epilepsy. She also studies pregnancy and contraception in women with epilepsy and is the site-PI of the MONEAD (maternal outcomes and neurodevelopmental effects of anti-epileptic drugs) study. Finally, she is interested in the use and understanding of continuous EEG monitoring in the critically ill and is the site-PI for the Critical Care EEG Consortium.

Q&A with Dr. Elizabeth Gerard and Dr. Gemma Carvill

Will genetic testing tell you if your type of epilepsy could be passed down if you have children or if it won’t be?

Oh, thank you. That’s a great question. And I want to say that the way I got into this space in the first place was that I was counseling patients about pregnancy, which is how I started my career. And I felt like I knew everything that they wanted to know about the seizure medications and about epilepsy, and that in most cases, pregnancies are very successful. And I realized pretty early on that I wasn’t answering all of my patients’ questions because so many patients have the questions about heritability. And that’s actually how I started working with Lisa Kinsley, our genetic counselor, and this clinic grew out of that. I will say, and this is something that we want to study, we’ve been learning that answering that question for individuals is not as clear cut as it might seem, and I’ll kind of go through some of the reasons why the short.

So the first thing to know, is that if you don’t have genetic testing, depending on your epilepsy type, the chances of passing on epilepsy is not terribly high. We know that for studies of big populations of patients. That of course changes if you have many individuals in your family with epilepsy or you have specific types of epilepsy that are more likely to be genetic. So in those situations, we do recommend genetic testing to help you better understand what the cause of your epilepsy is and what the heritability of it is.

One of the reasons it’s tricky, and I want to compare and contrast this with, say for example, prenatal genetic testing you might do with an OB, is that our understanding of what’s called the penetrance of these disorders is slightly different. So we may have, in some cases we diagnose a genetic epilepsy that’s associated with a single gene and you have to have only one copy of that genetic change to be at risk for epilepsy. And those are the type of genetic changes that we often diagnose if we are diagnosing a genetic condition, and those pass to each individual 50% of the time.

However, just inheriting the variant or the genetic change doesn’t necessarily mean the individual will develop epilepsy. So we get into this probability model where it’s like, “Yes, we made the genetic diagnosis, yes, you have a 50% chance of passing this on.” And again, this is rare, it doesn’t happen often, but the likelihood that your child who inherits it will develop epilepsy can be variable, can be 60% in some of the situations that we deal with.

And so yes, it helps. It helps to understand the inheritance pattern. It helps to understand your genetic diagnosis if you have one. Another example is you may find out that your epilepsy is due to a recessive condition, and if it’s due to a recessive condition where you inherited a genetic change from mom and dad, the chances of your passing it on are very low.

But we are learning that because there’s so much uncertainty in our results, including the variance of unknown significance, including the likelihood of genetic change causes a condition, that a lot of times it’s not black and white as it is in some other forms of sort of prenatal genetic testing. So that’s why that if you’re doing genetic testing with the thought process of, “What’s the risk to my child going to be?”, that you do this very carefully with a genetic counselor and someone who understands how to explain this. And this is where I think it’s really important that your perspective partner also come to the visit as well.

Is there a way to use the Northwestern team for genetic testing if we are in another state?

Take that one, too. So, we’re very excited and we’re hoping to expand this. We do a lot of our consultations virtually now. We also do some in-person. And it’s not just me, I’m really happy to say that Dr. Scott Adney has joined me and we have other people who are hopefully going to join our team as well. I’m licensed in a few states, but not all. And if you’re not in a state where I’m licensed, then you can travel to Chicago if you’re willing to come and see us.

I will also say that interest in this type of specialized clinic is growing and there are several others throughout the country. I just want to highlight some of my colleagues at University of Pennsylvania, University of Alabama and Stanford are some of the people I work with. So if you’re in one of those regions, I’m sure there are more developing, but these are people I know and work with who are doing something very similar to us.

Would genetic testing help determine which medications will help?

So in the psychiatry space and sometimes in the neurology space, there are tests which tell people how you’re going to metabolize drugs. I think it’s important to understand that that’s different than what we’re talking about here today.

Yes, sometimes if we make a specific diagnosis of a genetic condition, there already are specific treatments, including the ketogenic diet or specific medications that you should try or not try based on your genetic diagnosis. Dr. Carvill also talked about that we’re more and more gene therapies that are developing, but in many cases, making a diagnosis does not yet lead to an immediate treatment, just like Maggie spoke about. It’s more the hope for the future.

Would genetic testing help with diagnosis with somebody with generalized seizures? And what type of genetic testing should they start with?

Do you want to try that? Still me? Okay. Actually, I don’t know if we can share or if you want, but I had in the extra slides, the sort of algorithm that’s recommended by the Genetic Counseling Society to go through testing in general. As I said, that the genetic generalized epilepsy, so I want to first make a distinction. Many patients have generalized seizures, so generalized seizures can occur in a bunch of different disorders. Sometimes we refer to the term generalized seizures just because you have a convulsion. So I don’t want to presume that having generalized seizures means generalized epilepsy. Generalized seizures occur in all genetic conditions as well. So, generalized seizures certainly don’t preclude testing.

Having what we often call a genetic generalized epilepsy or idiopathic generalized epilepsy, some of the examples of that might be, for example, juvenile myoclonic epilepsy. It’s a combination of having epilepsy usually with convulsions and certain features on your EEG, usually without developmental delays. That particular group of patients has a lower chance of having a positive result on genetic testing right now with what we have available. Doesn’t mean you shouldn’t do it, I think that’s a nuanced discussion we have with our patients, but I would put that way under 5% of getting a positive result.

Which test to do first, I think depends. So the Society of Genetic Counselors recommend for all epilepsy genetic testing now, to ideally start with either an epilepsy gene panel or an exome or genome test. That may be hard cell for the idiopathic or genetic generalized epilepsies. I also would mention that a microarray, which looks for deletions and duplications, like Maggie was describing, if you’re really questing for an answer, I’ve actually found that test to be useful in the generalized epilepsies. Again, with the implications of the results being somewhat variable

This one is related to Ring 20, and it’s recognized that it’s very rare, and in this case it’s a somatic mosaicism. Is anybody researching this specific type of epilepsy?

So, I’ll make one point while Gemma thinks about that, but I’m ultimately going to toss it to her. One point about the ring chromosomes, as I mentioned that if your testing is negative, make sure that every stone has been unturned. Ring chromosomes are extremely rare disorders, can happen in multiple different chromosomes. And there are societies for several of the ring chromosomes disorders, but that is one of the diagnoses that would not be picked up with our big test, with our exome or genome. You actually have to do a very old test called a karyotype to diagnose ring chromosome.

And Lisa and I are unfortunately finding that less and less companies are offering that because it’s not been offered as much. So we’re actually trying to make that diagnosis on a patient right now. So it’s just an interesting point, that a karyotype is the only way to diagnose ring chromosome. As to specific, we are not doing work that I know of at Northwestern on ring chromosome disorders, but there is definitely research and groups working on it. And I was now waiting for Gemma to come up with who they are.

The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified healthcare professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified healthcare professionals who are familiar with the individual’s specific health situation.