Overview and Prevalence of Dravet Syndrome


Kelly Knupp, MD, provides an overview of Dravet syndrome and shares insight on discerning the diagnosis of disease from febrile seizures.

Joseph E. Sullivan, MD: Hello, and thank you for joining this NeurologyLive Cure Connections program titled Dravet Syndrome and Lennox-Gastaut Syndrome: Perspectives from the Patient Journey. Dravet syndrome is a rare and severe form of epilepsy that begins in infancy and continues throughout the lifetime. It is characterized by frequent often prolonged seizures that can be provoked by fever and may affect one side of the body. The majority of patients with Dravet Syndrome have pathogenic variants in the SCN1A gene.

Lennox-Gastaut Syndrome, often abbreviated as LGS, is another epilepsy syndrome that presents in childhood and persists throughout adolescence and adult years. Patients often experience multiple types of seizures, including stiffening of the body or temporary loss of muscle tone and consciousness, both of which often result in a fall. LGS can be caused by a variety of underlying conditions. In many cases, no cause can be identified.

My name is Dr. Joseph Sullivan, and I'll be your host today. I am a pediatric neurologist at the University of California, San Francisco Pediatric Epilepsy Center in San Francisco, California. I'm joined today by a colleague and friend Dr. Kelly Knupp, who's a pediatric neurologist at the University of Colorado School of Medicine in Aurora, Colorado. We are also joined by Mary Anne Meskis, also a friend and colleague, who is the founding member of the Dravet Syndrome Foundation, and her son has Dravet Syndrome. And lastly, we are joined by Dr. Tracy Dixon-Salazar, also a colleague and friend, who is executive director of the LGS Foundation; Dr. Dixon-Salazar is a neuroscientist and geneticists, and her daughter has LGS. Thank you all for joining me today; it's great to see you all. Let's get started with our program.

Our first section is going to be on Dravet Syndrome, and I really want to first start out with an overview, and how we start to suspect the diagnosis. Then, we will start to get into more of the details of why this is a syndrome, why it's more than just seizures, and how all these different aspects of the syndrome have an impact on quality of life. Kelly, maybe you can just start us off by giving an overview of Dravet Syndrome, how common it is, and the early symptoms and signs that we should be aware of.

Kelly Knupp, MD: Dravet Syndrome is a developmental epileptic encephalopathy that usually starts in the first year of life. It is most commonly characterized by seizures, of which there can be of multiple types, many of which are provoked by changes in temperature. We also see intellectual impairment that may actually be more apparent as children get older, which I think is really important when we're thinking about diagnosis, because we may not see that component early on. We can also see a progressive gait disorder, as well as behavioral disorders and a number of other comorbidities.

One of the characteristics of this syndrome is that it's often associated with a pathogenic variant in a gene called SCN1A. The vast majority of children do have one of those genetic diagnoses, but not all children. That's important to keep in mind, as well that there's a clinical syndrome, but we may not find a genetic mutation that goes along with it. It is also important to know that there are some children who have a pathogenic variant in SCN1A, who don't actually have Dravet syndrome. It's important to look for both of those things: the clinical syndrome as well as the gene mutation. Initially, we thought this wasn't very common, that it was present in about one in 40,000 children. Some recent data suggest that it's more common than that, perhaps about one in 15,000. It is something that we see in most practices, and I worry when people tell me that they haven't seen Dravet Syndrome in their practice, because I think they're probably missing it.

Joseph E. Sullivan, MD: Absolutely. We are of similar age and trained at similar times. When I was in training, I probably saw one child with Dravet Syndrome, which means we missed a lot of them. It’s almost embarrassing, but you can see how it happens. We are told as pediatricians that febrile seizures are common and many of these kids are told not to worry about it. Could you go into a little bit more detail? In 2002, with everything that we know, when should we not be thinking this is “just a febrile seizure”?

Kelly Knupp, MD: I follow a child in my practice, and I remember having a conversation with this child’s mom about how common febrile seizures were. I felt really comfortable that this was febrile seizures, and, in the end, it was not. Many of us have had that experience. In my mind, any child who's had a prolonged febrile seizure, particularly if it's one side shaking more than the other a hemiconvulsive seizure, we should think about doing genetic testing. For any child who's had 2 or more febrile seizures, if one of them has been prolonged, we need to think about doing genetic testing. I'm on the fence about the children who have had 2 simple febrile seizures and otherwise are doing well, because we know that about one-third of children who have a first febrile seizure will go on to have a second febrile seizure. But, if there's something like a prolonged seizure, or a focal nature to the seizure, we have to consider doing genetic testing.

Joseph E. Sullivan, MD: Age is a factor, too. We're told that febrile seizures occur at six months, if a patient has a simple febrile seizure at six months and then another simple febrile seizure at seven months, that's a worry to me.

Kelly Knupp, MD: That would start to make me a little anxious, too, I agree. Having them so close together would definitely worry me too.

Joseph E. Sullivan, MD: Classically, we used to think that Dravet syndrome only presented at less than one year of age. But now, with the ability to get genetic testing, we understand the evolution of a syndrome a little more, and it's clear that patients are presenting at a later age, although there still is kind of this sweet spot time, or age, when kids present.

Kelly Knupp, MD: Even for those older children, their parents usually are able to describe some sensitivity to change in temperature, which may not necessarily be a febrile illness, but can be other things, such as getting in and out of the bathtub. Whenever I hear somebody who describes their child having seizures when getting out of the bathtub, we should test for Dravet syndrome. Or for patients going in and out of the grocery store or Target, where that heat is blasting down on top of them, as soon as I hear that in history, I always need to look closer. Genetic testing for most of our patients in this age group is so readily available, even if insurance doesn't cover it. We have programs like Behind the Seizure, where it is relatively straightforward to get genetic testing in this cohort. Unfortunately, that doesn't help our older patients and adults, where this history may be difficult to tease out.

Transcript Edited for Clarity

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