The Importance of Seeing Rare Disease Patients Holistically: Eric & Kristi Levine, Parents of a Child with CACNA1A

Michael  Carrese 

Hi, I’m Michael Carrese, welcoming you to Raise the Line with Osmosis from Elsevier, an ongoing exploration about how to improve health and healthcare. 

We continue our Year of the Zebra series today by introducing you to a rare genetic mutation called CACNA1A which can cause muscle weakness, migraines, paralysis and even life-threatening seizures. Many variants can also cause neurodegeneration. 

Joining us to help us understand the disorder and its implications are Kristi and Eric Levine of New Jersey, the parents of two children, the younger of which was born with CACNA1A and is currently the only known person with his particular variant.  

Kristi and Eric both work full time and have becoming experts at juggling work, caregiving, parenting, advocating, and volunteering with the CACNA1A Foundation. 

Thanks very much for joining us today to share your family’s story and raise awareness of this disorder. 

Eric Levine 

Thank for having us. 

Kristi Levine

Thank you.

Michael 

So I'd like to start with learning more about you and your lives before your journey with your son's health issue started. So Eric, perhaps you can kick us off with that.

Eric 

Kristi and I met at the end of 2010, both lovers of live music and of the band Phish. So we met through mutual friends at one of their concerts, started dating, got married in 2013, had our daughter Stella at the end of 2015. And then to the summer of 2022 is when Trey was born. 

Kristi

I'm a teacher. I teach Montessori, 3 to 6 year olds and I have a masters in early childhood development. So, I spent most of my time with kids and observing them a lot and understanding how they develop and helping families through the process of education and supporting their kids as they grow. So, when Trey came, it was pretty apparent to me that something was going on with him just from being around children for so long and understanding how they grow.

Michael 

And what are some particular things that you picked up on?

Kristi

So I know infants’ eyes sort of wander when they are first born, but as he grew bigger, he was about four months old, and his eyes were still wandering and they were doing some movements that weren't necessarily normal. So, we went to our pediatrician and I pointed it out to her and she agreed that we should go to an ophthalmologist and get it checked out. 

It was about our second visit with our ophthalmologist that she took a look at Trey and was like, it might be a vision issue, but I think it's more than that. So we think that you should go down to CHOP, which is the Children's Hospital of Philadelphia, and they have world renowned doctors. They will give you the best care. So we took a trip down to Philly and met with a neuro ophthalmologist there because she felt like it was it more than just his eyes and that was when we sort of started the whole diagnostic process of figuring out what was going on with him. 

We did an MRI and we did an EEG. We thought he was having seizures because of the way that his eyes move -- they sort of like rolled back into his head and it looks like he's having a seizure – so we did an EEG to make sure, but his eyes did that several times during the EEG and it wasn't considered a seizure activity. So we kind of went on from there and it was at that point that they said with the eye movement issues and the fact that he was missing so many developmental milestones, they felt like it would be a good candidacy for genetic testing. 

That's when we met with the geneticist and did all the blood samples and Eric and I were both tested. Trey got diagnosed with cerebral palsy before we did the genetic testing because of the way that CACNA1A affects his movements -- it looks pretty similar to a child who would have cerebral palsy -- but once we got the genetic results back, we found out our answer.

Michael 

We've talked to lot of folks on this show who have a rare disorder themselves or their child does, and as you guys I'm sure know, it can take years and years for physicians to pinpoint it. At least you didn't have five to seven years like other folks, but still that's a...

Eric 

It's tricky though, we've heard that from parents and doctors, ‘I’m glad you guys caught it so young’ but for us, we were just that whole time just waiting for a diagnosis, thinking we had it with the cerebral palsy, so it seemed like forever for us.

Michael 

Well, and I was going to say, but it really doesn't matter because you still have all that anxiety and the unknowns and thinking, you know, it could be a million other things, you know, and not having any idea. So that's a rough road. So, I said in the introduction that he's the only one they know with this particular variant. Help people understand just how rare CACNA1A is, generally speaking.

Kristi

So, CACNA1A is actually the abbreviation for the gene. So it's the calcium channel and that affects the calcium channels within the brain, primarily, and in the cerebellum. So it affects things like his motor skills, his balance, his coordination, his posture, and his speech. 

They actually think that if more people were tested genetically for CACNA1A, that actually it wouldn't be as rare as it is. What makes it interesting is that there's so many different variants of the gene. So Trey's particular variant, they haven't found anybody else who has that same variant. And that's pretty common for most kids and most people who are diagnosed with CACNA 1A related disorders. 

But there are a couple of variants that they found are replicated in people. those are the ones that they're mainly spending their time studying and things like that...you know, the disorders that it causes are on the more severe side. It's things like epilepsy, something called a hemiplegic migraine -- which is basically like a stroke...it's paralysis on one side of the body, and that can lead to a loss of skills which they would work to gain back – and episodic ataxia. 

Luckily for us, Trey hasn't really exhibited any of those more severe symptoms. We're always on the lookout for it and we're always sort of in the back of our minds thinking, ‘is today gonna be the day that he has a seizure’ or whatever. You know, we have like these action plans with our medical team just in case it happens because they found with people with CACNA1A, it could happen at any age. It's not like it just happens in infancy. There's children who will have their first seizure when they're three, four.

But for Trey, his main symptoms are the eye movements. So he has something called paroxysmal tonic upgaze, which is that sort of rolling back of his eyes. He has hypotonia, so his muscle tone is very low. He has ataxia, so his balance is off and he has just global developmental delays. He's nonverbal, he's not ambulatory, so he's not walking. Cognitively, he's right where he should be at his age. He's almost three years old and cognitively he understands. But he gets very frustrated that he can't communicate what he wants and needs and that he can't move around like everyone else.

So those are the main things that we're working on. He is also missing his CN-6 which is the nerve on the left side of his brain that connects his eye to his brain. His eye on the left side is always turned in towards his nose, which affects his vision so he's in vision therapy for that. So, that's the main things that we're dealing with.

Michael (10 49.218)

Yeah, that's a lot on your plate.

Eric 

Just to go back when you asked how rare it is, about a month or two ago, for the first time we met a family who had someone with it, just to give you an idea. We’re one of the three known families that have someone with CACNA1A in their family in the state of New Jersey, so it's just it's very rare.

Michael 

Wow. Yeah, yeah. So what is it like as parents of a child like that? Eric, can you give us sort of a day in the life sketch, if you will?

Eric 

It depends on the time of day or the day of the week. Having our nine-year-old daughter helps a lot. She's a great help. She's also nine, so she has her needs as well. I think the most challenging thing Kristi just mentioned is he gets frustrated when he can't communicate what he wants. He's able to sign a few words and say, “Dad” or “no” or “yeah” but when he can't communicate, it's just constant screeching and screaming. Like, that's how he communicates. 

So it's definitely difficult to try to maintain positivity and energy while dealing with that, but I would say Kristi’s kind of become an expert on it. I'm an aspiring expert, I'm getting there. It's definitely tough.

In the past few months, we've gotten more involved with the CACNA1A Foundation, and that's just made a world of a difference, just to know that we're not alone. There's a lot of people like this. I'm getting more involved with the Foundation, trying to help them fundraise with different events later in the year, but that's been a huge help to us just knowing there's others out there. 

And it's worth mentioning with all the issues that he is one of the happiest kids, ever. He's always smiling when he's not screaming. He's smiling, laughing. He loves Blues Clues...like he can be the happiest kid on earth. But he just has to work so much harder for the most simple things.

Kristi

Yeah, he's incredibly social. So if you can imagine taking this like extraverted social kid, but not being able to communicate with others in the way that he wants to. His favorite thing in the world is giving hugs and being with other people. Like he's happy when we're out and about and he's at school with his friends and we're doing things, and then it's like when we're at home and just trying to like do the normal life things -- like get everything done for the week and cook -- that's when he loses it. He's like, I can't.

Michael 

Right, right. What are some of the management protocols, I guess, or strategies that you guys employ to help with all this?

Eric 

One thing -- this is kind of unspoken between us -- we're humans, so we both know what has to be done, but there's times where one of us gets overwhelmed, the other one comes in. We both have said ‘you take care of this, I'll take care of that’ but when it comes down to it, in the day to day, we're both just doing everything. We both just know what needs to get done. It's not like she has her things, I have mine. We're just all in hands on deck, just trying to make it work especially during the week, you know trying to get ready for work and school it's just, you know... 

Kristi

Yeah it's like survival mode basically. I mean we're both working and then Stella is sort of in a different plane of life. She's a tween now, so she's got her own things going on that we need to support. And, and they couldn't be more different as children. She's very active, she dances and she is very mobile, and he is not able to do those things. But she entertains him. 

And we have really set up our house to foster his needs as much as possible. So, he can access his toys independently. He's got his favorite things that entertain him. He loves his Tony box. He loves stories and songs and books. And so we've sort of set it up so that he can kind of play on his own and Stella will help him with that when we're just trying to like, you know, cook dinner or clean up or whatever it is that we need to do. We just make do the best that we can with what we have.

Michael 

What is happening on the research front and is there even a center out beyond CHOP where you guys have been able to get some assistance on all this?

Kristi

Yeah, so the CACNA 1A Foundation has been incredible. With the University of Texas at Houston, they just opened the first CACNA1A clinic recently, within the last month or so. So that was really exciting. I know that there's been some people in the community who have been able to travel there and have said that the team is incredible and super supportive and everybody's been amazing. We have not yet been able to travel to Texas yet but maybe one day in the future we'll be able to take Trey down there.

So, I think that's like the most important thing is like when we got our diagnosis, as wonderful as our geneticist was, she basically printed information off of the CACNA1A website and was reading it to me. Doctors with these rare diseases...they don't know about them. So, I'm trying to soak in all of this information about my child's diagnosis and they’re basically like, ‘here's a website that you can go to to find out more information.’ And we're so lucky that that was there, because in a lot of cases, there's nothing, like there's no website, there's no community, and a lot of parents are starting from the ground up and actually creating it.

Eric

Aside from CHOP, for us personally, that's it. Without CHOP, I don't know where we would be. And every doctor, whether it's in Hackensack or wherever we've gone, everyone has the best intentions, but it's the nature of it. Not a lot is known about it.

Kristi

When we got our diagnosis, basically what I did is I just went on to Facebook and I found the CACNA1A community and I was just looking for any doctor who knew about CACNA1A and luckily they had had a conference and I looked for a doctor who spoke at the conference who was within, you know, driving distance of New Jersey. And that's where I found Dr. Helbig and that's where I found CHOP. Basically that's where we constructed our medical team. Once you have a medical team established, you don't want to leave that. So now we're like, we have to stay near Philly. So.

Eric 

I just also want to shout out the CACNA1A Foundation. It's worth mentioning that Lisa Manaster and Sanath Kumar Ramesh both started the foundation during COVID from their couch. They are 24-7 working on it and without that dedication to get this started, just like with CHOP... I don't know where we'd be without them.

Michael 

Yeah, I'm glad there is some community, because we have run into folks on the show where they did exactly you described, Kristi. There was nobody else, and no resources and no information, and they had to go from scratch. It's amazing what people can do. 

So, before we started recording, I was noting that there was a big science story recently about gene editing breakthroughs that have potential implications for rare diseases across the board. Tell me what your understanding is about that and how it might or might not influence what's going on with Trey, but also tell me if there is any sense that there's work being done or is there anything on the horizon that might end up being applicable to CACNA1A?

Kristi 

From what we understand from researchers and scientists from the CACANA1A Foundation, gene editing for the liver is a lot simpler than editing something that affects the brain. And so as hopeful and as exciting as it is, it's a long way coming for patients. So, we're just gonna keep being hopeful and hope that research and different treatments become available over his lifetime. 

Right now the treatments that are available are few and far between. It's just basically managing the symptoms. So if you have epilepsy, there's treatments for epilepsy. If you have hemiplegic migraine, there's action plans in place for the emergency teams that would be dealing with that. There's therapies and things to help with the muscle weaknesses and the coordination and things like that. So, Trey's in all the therapies. He's in physical therapy, OT, speech, vision, DI, all of it. And, you know, we do the best we can and manage it and schedule it in as best that we can. But as exciting as things like the CRISPR gene editing are, it just feels really far away for kids like ours.

Michael  

Yeah, I hear that. Eric, you'd mentioned before that there's fundraisers and other stuff going on with the foundation. Do you want to give us a little bit more information on that or how folks can get involved if they want to help?

Eric 

Yeah, absolutely. There's some stuff that's tightly sealed and I can't talk about it yet. Kristi and I have known about the foundation since Trey's diagnosis, but we didn't feel like we were involved really at all other than just getting their emails. So I reached out to find out how we could help not just Trey, but the foundation in general. The main takeaway from our conversation was they need help fundraising.

When Kristi just mentioned that the promising research is still far away for us, it goes to show that that fundraising really matters. I mea, there's a direct result of fundraising. So what I'm trying to do now is organize. Right now I'm working on a concert for the end of the year. I want that to be the foundation and then continue with events next year dedicated to not just raising money but raising awareness because like Kristi said earlier, it's not as rare as people think it is. It's just that there's not enough testing and not enough knowledge out there. My mission is to just tell this story as much as possible and try to spread the word to the different audiences whether it's music fans or just people who wouldn't normally come across anything like CACNA1A.

Michael (25 36.054)

Right. Yeah, it's important work and you never know, as you make these efforts and the ripples go out, how they're going to connect and what can build off of that.

As you folks may know, we have a lot of med students, nursing students and others in the audience and also folks who are early in their healthcare career. I wonder what message you might have for clinicians about dealing with families that have a child with a rare disease? You talked a little bit about the encounters you've had and that have been positive, but you know, are there other things that you would want people to understand going into this world and giving them some guidance about how to approach it?

Kristi

I think being a parent of a child who's medically complex or disabled is really hard and I think we just want medical professionals to respect and to understand what we're dealing with on a day-to-day basis and to see our kids holistically. So, not just trying to fix the problem medically, but to understand that for us, the biggest thing that we want for our kids is just their quality of life. We just want them to live the best life that they can and feel supported in that. And yes, we would love if there was a quick fix for it, but we know that that's not the reality. And there's part of me -- I can't speak for Eric -- but there's part of me that grapples with wanting to quote-unquote fix our child because it's who he is. It's part of who he is. And if we take that away, is he gonna be the same person? So we just want to be respected. Sometimes I feel like we know more about it than the doctors that we're talking to...

Michael 

Which is probably true.

Kristi

Yeah, and you know, we just want to make sure that he's having the best life that we that we can give him and to not feel the guilt. There's a lot of guilt involved in being a parent of a child who's who has a disability because you never feel like you're doing enough and we're doing all that we can and we're giving so much of our time and energy to this, and it's just hard. 

So, we just want to make sure that if we have a difference in opinion, that that's being respected and it's not that we think that we know more than a medical professional -- obviously we don't -- but that our opinion is important and our child's quality of life is the most important thing. 

Eric

For me I just really encourage being real and honest. I'd much rather have professionals say ‘I have no idea what's going on’ than try to fake that they do know. But also, just to reiterate what Kristi said, respect holistically what's going on and not just the data and what's coming out, reports and whatnot. Yeah, just being real and understanding that we're parents.

Michael (29 37.646)

Yeah, and listening. 

Kristi

Yes.

Eric

Yeah.

Michael

We hear that a lot from other folks in your shoes. Well, as we wrap up here, is there anything else you wanted to talk about, or get across to our audience that I didn't ask you about?

Eric 
Yeah, we just want to shout from the mountaintops to make everyone aware of CACNA1A. I know from just living life that when you hear about a new multiple-syllable diagnosis and you have no idea what it is, it can kind of be easy to ignore or brush away but if you just do five or ten minutes of reading and understand what it is, you’ll know that there can be a lot more help than there is, that there should be a lot more help than there is. We just need more people to become aware of it to make that so. 

Kristi

Yeah. You never think it's going to happen to you until it does. It was a huge surprise to us When we were doing the genetic testing, we thought it has to be from one of us, you know?

And it was considered a de novo mutation which means that he's literally the first person in our family to carry it. So you just never think it's gonna happen to you until it does.

Eric
And there's no like, group huddle. Like Kristi said earlier on, we knew right away something was going on and it was deeply concerning every day, from when we first noticed the diagnosis until now. There was never a time where someone said, “Hey, your son has this, this is what it's like.” It's just day after day finding out something else he's not able to do, another milestone he's not able to reach, another diagnosis, and you just have to roll with it. You just have to move forward.

Michael 

Right, it's reality times 100, you know, as far as parenting is concerned. But it sounds like you guys are on top of all of it, and I want to thank you very much for spending time to share the story and help raise awareness, and of course, we just wish you all the luck in the world.

Eric 

Thank you so much. We appreciate you having us. 

Michael

To learn more, you can visit the CACNA1A Foundation at www.cacana1a.org.

I’m Michael Carrese.  Thanks for checking out today’s show and remember to do your part to raise the line and strengthen the healthcare system. We’re all in this together.