In this video, Jennifer and Derek discuss their son Ryan’s experience with seizures and the diagnostic odyssey that led them to the Epilepsy Neurogenetics Initiative at Children’s Hospital of Philadelphia (CHOP) for help.
Epilepsy is a common brain disease defined by the presence of seizures. For many children, the cause of epilepsy is genetic. Until recently, little has been known about the genes that cause the condition, so treatment has been imprecise and not targeted toward the underlying cause. Many families spend years searching for answers to alleviate their child’s suffering.
At Children’s Hospital of Philadelphia, we are dedicated to improving care for children with epilepsy. Thanks to recent rapid advances in our understanding of the role genetic variants play in epilepsy and the development of genetic testing technologies, we can now identify the genes causing a child’s epilepsy, which can put an end to a family’s search for answers.
Epilepsy Neurogenetics Initiative: Advancing Care Through Genetic Testing for Epilepsy
Jennifer, Ryan's mother: It was December 24th of 2011. Ryan was five months old and I was bringing him down the steps after his feeding, and I felt him go completely stiff in my arms.
At the time, I didn't think seizure. I just called 911 and we went to the hospital and so they decided to keep them and sure enough, the next day it happened again and they all saw it. And that's when he was officially diagnosed with the seizures.
The scariest part for me was not just watching Ryan have the seizure, but then also thinking "What could all of these seizures do to him?" I mean, he was having one after another, after another.
Ethan Goldberg, MD, PhD: Epilepsy is the disorder that's simply defined by the occurrence of seizures. And it's more common in childhood than in adulthood, and there are many causes. The brain is an electrical organ and all of our brain functions -- for example, our speech generation, our sensory perception, our voluntary movements -- are generated by electrical signals between brain cells.
Epilepsy can be caused by genetic variation in the building blocks of the brain that underlie that electrical signaling. And it turns out at least half of childhood epilepsy has a genetic basis. One of the major motivations behind the Epilepsy Neurogenetics Initiative, or ENGIN, is we're attempting to expand access to genetic testing to investigate that cause and deliver an explanation as to why a child might have epilepsy so that family can have an answer.
Nichole, Gregory's mother: His epilepsy was the hardest thing I've ever been through in my life, but knowing that we are the proximity we are to CHOP and we were able to get down here with this team and be a part of this ENGIN Program.
We knew to expect some delays, so he's going to walk a little later, crawl a little later, but it's not going to matter when he's five years old and running around with all his friends.
If anything, he's actually ahead in certain areas.
Shavonne Massey, MD: The impetus to start the ENGIN Program was to have this fusion of neurogeneticists along with epileptologists to sort of bring those two worlds together, to, to melt the expertise and sort of brainstorm the best ways that we can move forward, I think with clinical care and research.
Ingo Helbig, MD: She's actually quite strong.
What sets the ENGIN Team really apart is that we are one of the largest epilepsy genetics programs in the country. So we have the ability to see patients with known or presumed genetic epilepsies very quickly and really provide very detailed knowledge about the diagnosis and treatment.
Very, very nice.
Derek, Ryan's father: My understanding right now, there's less than 450 people worldwide with the same genetic mutation that Ryan has. So it's extremely rare. I mean, they vary from kids that are very, very disabled, to kids like Ryan that are functioning, able to live almost a normal life at this point. So it's very hard to, without the genetic testing, to even diagnose, because once we got the genetic testing, we were able to find out the medications that worked for him.
That's the great thing about CHOP -- they're doing all the research, they're getting you all the opportunities to find answers. And we're, you know, we're able to use them to help try those different opportunities to make that happen.
Ethan Goldberg, MD, PhD: Hello. Hi Leah. How are you guys doing?
Leah's mother: Good, how are you?
Ethan Goldberg, MD, PhD: There are a range of treatment options that we can offer at CHOP. One of those is an anti-seizure medication. So a small molecule that is tailored or targeted towards that particular genetic finding that might stop that child's seizures, that might improve their neurocognitive development.
I'm trying to remember the last time we saw Leah was back in February was it, I believe?
Leah's mother: Yeah.
Ethan Goldberg, MD, PhD: How have things been going since then?
Leah's mother: Still no seizures.
Ethan Goldberg, MD, PhD: In some cases, a genetic diagnosis will allow us to enroll a child in an investigational trial or a study of a novel or investigational compound.
Ingo Helbig, MD: It is very critical to treat epilepsy and seizures as soon as possible. If seizures are not treated, they may be damaging to the brain. They may impair a child's ability to learn and this is why it is critical to treat epilepsy as soon as we identify it. Genetics comes into play to help find the best treatment options and to make sure that patients are really on the medication that they tolerate best.
Erin, Lucy's mother: It's just been really helpful to have people that have seen kids like Lucy.
There's not very many of them in the world. And so having someone that does have experience and expertise with kids, like this is helpful when you feel like you're kind of alone and you don't really know. What end is up.\
Ingo Helbig, MD: The issues that she's having right now, they're tone issues. They're not strength issues.
Shavonne Massey, MD: I think the other nice part is that we have a multidisciplinary team, so we have social work, we have child life available in our clinic. Along with the physicians, we have the genetic counselors who are seeing the family along with PT/OT. So there's a large team. And sometimes when families are having difficulty coping or maybe don't have a great support system and so need more support from us.
I think the genetic counselors are the heart of the ENGIN Program. Their breadth of knowledge is unparalleled and vital to our interactions with the patients.
Ethan Goldberg, MD, PhD: The Children's Hospital of Philadelphia has a very large inpatient EEG unit where we do video monitoring, where we simultaneously record the electrical activity of the brain noninvasively.
And that parent can be comfortably staying with the child in the room. And they can say "That is what I am concerned about."
Shavonne Massey, MD: Genetic testing is absolutely an option for families of older children and even adults who have never received a formal cause for their epilepsy.
Lavish, Kashvi's father: People treat like in a very, you know, good way, the doctors, especially, the staff members, they treat very well and, they have a proper plan so it's a great experience.
Shavonne Massey, MD: There are many causes of epilepsy that we know about today that we did not know about when these children were born and initially diagnosed with epilepsy. And so having a new set of eyes, evaluate them with a new sort of armamentarium of genetic testing and different modalities has a higher chance of finding an answer for them.
Ingo Helbig, MD: So we are able to find an answer for a child's epilepsy in maybe 30%. However, this means that we're not able to kind of provide an answer to families in more than two thirds of the cases. What I typically tell families is that finding an answer, finding a genetic diagnosis, is a journey. This journey can be answered very soon with a positive finding, but in many cases, we have to look at genetic testing over and over again.
Ethan Goldberg, MD, PhD: For those patients who are teenagers and older ...
Ingo Helbig, MD: Over the last 20 years, we've seen a tremendous change in epilepsy genetics.
20 years ago, we had maybe one or two genes. Today we have more than 500 genes we can test for. Only a decade ago we had to turn patients away and say we can only do one test at a time. Now we can do all these tests in parallel and to get to a diagnosis much faster. My research lab is largely focused on understanding the genetic epilepsies that we're not able to answer straight away.
We do a very sophisticated computational analysis on genetic data and we try to really understand, is there anything hidden in the genetic data that may explain a child's epilepsy?
Most patients have seizures really in the first year of life.
Jennifer, Ryan's mother: Having the genetic testing done and getting those results has made a difference for him.
Science is finding that there are some medications for the large, large majority, if not all, it makes the seizures worse. So that alone is great information to have. And then it, on the other end, there's a medication that tends to be the most successful for most children. I think having that diagnosis has been extremely lifesaving for Ryan.
I don't know that he would be where he is today, without that testing. It gives children like Ryan a chance. I truly believe that without programs like ENGIN, Ryan would not be functioning the way he is. I think it came around at just the right time for him. So, it's saving lives.
Related Centers and Programs: Epilepsy Neurogenetics Initiative (ENGIN)