Joseph E. Sullivan, MD: Mary Anne, I'd like to actually pivot to you and have you reflect back on what you were told when your son had his first seizures. Does this create some flashbacks for you?

Mary Anne Meskis: Definitely flashbacks. I would agree with Kelly; I think certainly in the last decade, we've really seen a change in the typical journey for patients and parents to get to diagnosis. Back then, my son (who is now 22), was not diagnosed until age 4. Early on, we kept being told that it was febrile seizures. Unfortunately, we still have some patients that follow that same diagnostic journey; if they're not being seen by a health care professional that understands what they should be looking for and doesn't order genetic testing, unfortunately it can still take several years until symptoms progress and until they find the right specialists that can help them get to diagnosis.

Joseph E. Sullivan, MD: With genetic testing, just five or six years ago, it was a month-long process of being able to get it, yet we were still able to make the diagnosis of Dravet syndrome then. And Kelly, I'm just curious, at what point did you start to say, "OK, I frustratingly cannot get genetic testing, but I'm confident you have Dravet syndrome, and here's why.”?

Kelly Knupp, MD: I have lived in a place where we were very fortunate with early genetic testing for a long time. But for our older patients, seeing that 4-, 5-, and 6-year- old children who maybe didn't have genetic testing, the history of evolution from prolonged febrile seizures into multiple seizure types, the temperature sensitivity: I think we had huge confidence in that. The area where genetic testing has been really helpful has been with those very early seizures. It sometimes is challenging to tell the difference between a straightforward febrile seizure versus a febrile seizure associated with Dravet syndrome, particularly if it was not a hemiconvulsive seizure. But if I saw a patient whose first febrile seizure was a hemiconvulsive seizure on the right and their second febrile seizure was a hemiconvulsive seizure on the left, I would have felt really confident that it was Dravet syndrome, and that we should proceed as though that was the diagnosis.

I've seen a number of teenagers who weren't even seeing me in clinic, and they were being walked in the hallway by another provider, and that also is a very characteristic gait. I've made the diagnosis a handful of times in that setting, as well, where I've seen somebody walking in the hallway, and we've been able to tease out the history and make that diagnosis. I think there's some key characteristics that are very unique to Dravet Syndrome.

Joseph E. Sullivan, MD: We’re going to get into it a little bit more here. I also have a harrowing story of one of my patients. It was at a time when I had been following about 25 or 30 patients with Dravet syndrome. I had one family come in, there was a newspaper article on one of my patients who had Dravet syndrome. This patient was 17 and I inherited her in this practice when I started my job. In the chart, it just said, “refractory epilepsy, unknown cause.” She said, "Why couldn't you know my daughter had Dravet Syndrome"? I said, "She didn't have these alternating seizures with fever." And she said, "Yes, she did. The story goes on, even as I tell the story, the hair stands at the back of my neck, because I knew she was right. I didn't even need the genetics. I said, "You do have Dravet syndrome, and I am looking you in the eye, and I missed it." I think having that understanding of the different stages of the syndrome and how it evolves over time is certainly helpful for us, as we talk to families in terms of what we can maybe anticipate.

In terms of adults with Dravet syndrome, and it's certainly under diagnosed. I often think that there are hundreds, probably thousands of Dravet patients sitting in our very well meaning, reputable, bright, adult epilepsy clinics. They don't have the luxury of having that early childhood history. I'm wondering, Mary Anne, both in your role as a parent and also your involvement with the Dravet Syndrome Foundation, what stories are you hearing about this journey that different families have taken?

Mary Anne Meskis: With our adults, a lot of times it is parents that continue to push for answers. For families, often they get to a point of, I don't want to say complacency, but they become comfortable that they're managing seizures or offering the best quality of life they can, and they don't think necessarily a diagnosis is important. Sometimes I think physicians feel the same way that if the patients are in a much better spot than they have been previously, why are we still looking for an answer?

I would agree with you that we have a lot of patients that either are misdiagnosed, perhaps with LGS or another syndrome, or just have an idiopathic epilepsy diagnosis. The detriment to our community, of course, is that, for instance, since 2018 we've had 3 new treatments come to market for Dravet Syndrome. Here is an opportunity that we might be able to improve those patients’ quality of life. I have also heard from parents who kept pushing for testing, and after finally getting testing and a diagnosis, they might have had a child on a medication that was contraindicated for Dravet Syndrome for many years. I think there's a challenge, and I think that we still have to work to educate our adult providers about the importance of getting a diagnosis and making sure that they know this testing is available and is significantly less costly than it was in the past, because that was a barrier for a long time for our families.

Joseph E. Sullivan, MD: Absolutely. There's obviously some value in having a precise, accurate diagnosis, not only to treatments, like you said, but then just the sense of community, to be able to reach out to other parents who are living with the same day-to-day struggles. I've just seen so much value in that. It used to be patients would be sent to me, refractory epilepsy or someone would have some genetic testing and they were maybe thinking that was Dravet or Lennox-Gastaut, and they would come as a second opinion. But now, thankfully, due to the Behind the Seizure program, and at least the value of doing early genetic testing, now these patients are getting diagnosed earlier and coming to our centers with this diagnosis in hand, so that we can then walk through with them the next steps with regard to treatment.

Transcript Edited for Clarity