Joseph E. Sullivan, MD: We focus a lot on seizures because we're epilepsy specialists, but it's a syndrome. The reason why it's called a syndrome is because there are other clinical signs and symptoms that go well beyond seizures. Kelly, what are what are some of the things that you start to talk to families about or that you're looking for? You're taking that history, even in a patient who maybe comes to you after their second or third seizure, that are not seizure related, or at least not directly seizure related?

Kelly Knupp, MD: I think there are a number of things that evolve over time, just like the seizures evolve over time. I often try to talk to families about that big picture from the very beginning. And, when we see these children, and they're young, from a behavior standpoint they tend to be really active kids; they're hard to contain. I like seeing them in clinic, because they are fearless. They come on my lap, and they're not afraid of me, unlike all my other patients who are terrified of me, so I enjoy that. But I realized I am only seeing them for 30 minutes, I don't have to live with them 24/7. I think it is an important thing to talk about. Many of these children have constipation, which is important to talk about, many of the children have go through food fads, which initially is not an unusual thing for a 2-year-old, who's just getting diagnosed with an epilepsy syndrome. But it is important for parents to recognize that this may persist throughout their lifespan and change over time. From a pain standpoint, many of these children are relatively insensitive to pain, and I think that's a really important thing to point out to families early on. I have had a number of patients who have had significant injuries that have gone relatively unnoticed, because the children haven't complained about them: burns, fractures, things that if you aren't aware about the insensitivity to pain, you would know to look for these kinds of things. I think it is a really important thing to continue to remind parents about, so that they are checking to make sure that the AFOs aren't rubbing into their skin because the kids aren't going to complain about it, if that happens, and keeping them away from the stove, because when they touch the stove, it doesn't hurt as much as it does another child and I think that also impacts some of their sensitivity to other children.

This is probably just my theory, I am not sure I have seen this published, but I think it is hard for them to be empathetic about what hurts their siblings because it doesn't hurt them. It is hard for them to realize when I hit you and pinch you, it hurts and therefore I shouldn't do that because it doesn't hurt them when somebody hits them or pinches them. I think that's an important thing for parents to watch for. Many of these children do have intellectual impairment, I don't think that that is often present. They're at very young ages, many of the children are making developmental milestones just like we would expect them to. And, it's often not until early school age years that they really start to diverge from their peers. I think that's really important for providers to recognize as well. I think we have all seen patients and heard from families that they were told by somebody that you look too good to have Dravet, and the truth is at a young age, the seizures may be spaced out enough. Intellectual impairment isn't yet present. If that is what you're looking for in a 2-year-old, you are not going to see it and you are going to miss the diagnosis because we typically don't see that until later on. That behavior, as the children get older, slows down a little bit, and so we don't see the little busy bees that we see in the toddler years, and many of the kids actually get kind of sluggish and slow down and don't move as much. That is an important thing to prepare families for as well, that they may need help with mobility, particularly if they are doing big family outings at the zoo, that the children are probably not going to have as much stamina to do that when they're eight as they did when they were three, and to make sure that they have appropriate assistive devices for that. We have already mentioned that we see progressive gait abnormalities in these children, and that's also important for families to recognize. I feel like I'm missing some things here that I am not thinking about that I'm sure Mary Anne you could probably add some in because you have lived with this.

Mary Anne Meskis: There are just so many. As they get older, there are different needs. This disease is constantly evolving. It is trying to figure out the best way to navigate life at that particular point in time. There are no road maps, there are just a lot of unknowns.

Joseph E. Sullivan, MD: I think there was a video that the AES put together, they had the kids – because really, I think there is a barrier. Even today, 2022, with everything that we know about Dravet, if you go into Google and type Dravet, the top 20 hits are catastrophic. And so, this beautiful 12-month-old, how could they have a genetic variant that can lead to this catastrophic syndrome? I think not only can that be a barrier to diagnosis, but I think it also creates, for families now that come to me after their second or third seizure, they have already read all this stuff. How do we acknowledge that, all of those posts are real, there are people living this? I think it is our hope that we are in a different spot today than we were 5, 10, certainly 20 years ago.

Transcript Edited for Clarity