To help raise awareness of this rare genetic cause of neurodevelopmental disease, M. Scott Perry, M.D., medical director of neurology and director of the Genetic Epilepsy Clinic at Cook Children’s, shares basic information about the disorder and exciting advancements towards treatment for this rare disease.

What do SCN2A-related disorders look like? 

Children with genetic variants in SCN2A can develop early onset epilepsy with various levels of severity. SCN2A was first discovered as a cause of benign familial neonatal infantile seizures (BFNIS), a syndrome that often occurs in multiple family members. These children can develop seizures as newborns or infants, but can develop normally with good seizure control.

Later, SCN2A was discovered as a cause of infantile spasms and other early onset severe epilepsies of childhood, the so-called early infantile epileptic encephalopathies. The gene has also been linked to Ohtahara Syndrome, Dravet Syndrome, Migrating Partial Epilepsy of Infancy and West Syndrome amongst others. In addition, SCN2A variants are a major cause of intellectual disability, schizophrenia, and autism which may occur without associated epilepsy. A variety of other medical conditions may be present in people with SCN2A-related disorders, including sleep problems, cerebral palsy, and movement disorders to name a few.

What is the cause of SCN2A-related disorders? 

SCN2A is a gene which makes a sodium channel found primarily in the nerve cells that generate electricity. Two issues can occur with SCN2A. The first is a change in the gene which causes a gain of function – a change that allows too much sodium to enter the nerve cell and thus increases electricity – often presenting with epilepsy as a main symptom.

For others, SCN2A variants cause a loss of function – a change that decreases sodium entering the nerve cell and thus decreases electricity – more often presenting with autism and intellectual disabilities. Many mutations in SCN2A are de novo, meaning they occur spontaneously and were not inherited from the parents. This is often the case in more severe disease presentations. There are instances where SCN2A may be inherited from a parent and this is more commonly seen in benign presentations such as BFNIS.

How are SCN2A mutations diagnosed? 

Often, genetic testing can diagnose SCN2A mutations. The Behind The Seizure program provides free testing for children in the U.S. under the age of 8 years.

Magnetic resonance imaging (MRI) scans are often normal and electroencephalogram (EEG) findings may vary.

Is there a treatment for SCN2A-related disorders? 

While there is not yet a cure for SCN2A-related disorders, a significant amount of research is leading to exciting new therapies. Certain traditional sodium channel seizure drugs (for example, phenytoin, lamotrigine) have demonstrated more favorable responses for seizure control in select patients (often gain of function), while in others, sodium channel drugs may aggravate seizures.

New drugs are being developed that specifically target the abnormal channel produced by SCN2A. These treatments may provide more precise control of the channel without disrupting the function of other sodium channels like many traditional sodium channel seizure drugs. This may result in better seizure control with less side effects.

Potentially most exciting is the development of genetic approaches to therapy, treatments that don’t just treat symptoms, but aim to correct the genetic abnormality. Antisense oligonucleotides (ASO) are small pieces of genetic material that can be given to help increase or decrease production of SCN2A. This approach has been used in other genetic conditions (spinal muscular atrophy and Dravet syndrome) with success and represents a promising therapy for SCN2A disorders as well. This is just one of several genetic approaches to therapy on the horizon.

Where can you find more information about SCN2A disorders?

For more information about SCN2A and SCN2A Awareness Day, visit www.scn2a.org. The SCN2A Foundation serves as an excellent resource for information about SCN2A related disorders and helps connect a community of people living with these rare conditions. The site provides updates on SCN2A research as well.

“Virginia has intractable localization related epilepsy or drug-resistant epilepsy. If we break that down, that means she has epilepsy that has been uncontrolled by two or more medications,” said M. Scott Perry, M.D., medical director of Neurology and the Genetic Epilepsy Clinic at Cook Children’s. “’Localization related’ meaning it arises from one area of the brain, as opposed to the entire brain at one time.” 

In early December, Virginia had minimally invasive brain surgery. It’s been nearly three weeks and for the first time in 16 years, she’s seizure free.

“We did laser thermal ablation. This means we used electrodes to pinpoint the problem area and used a laser fiber to burn that area of the brain,” Dr. Perry explained. “She went home the next day. Now we enter the patient waiting game to see how it’s going to go.”

Though epilepsy is common to children, Virginia’s story is unique. She says she was in 4th grade when she realized how much impact seizures had on her life. She began looking down on herself and looking at herself differently. She felt as if she wasn’t the same as her peers in a bad way.“

When I was younger, I definitely hid a lot more, because I was afraid that people would look at me a lot differently. I only really told people if they were coming to sleepover. As I got older, I told more people, mainly my friends and I began accepting it more,” Virginia said. 

As years passed, things became normal to her. She played field hockey with her friends and was able to do most of the same things as her peers. It wasn’t until her sophomore year in high school when the “different” feelings came up again, because her friends were beginning to drive. 

“I really noticed it again when everyone was getting their permits. But when I was a junior, things were back to normal again because driving was routine and not everyone was excited about it anymore,” Virginia said. 

Virginia’s mom, Kate, has been her advocate every step of the way. She said when Virginia first started having seizures, she thought she was just making a funny face. Her dad was holding her the next day, and it happened again. When they took her to the doctor, Virginia had a seizure in front of them and the neurologist. It was then that they started on a path to find out the cause.

 “It’s very hard to watch a child suffer from a disease that is tragically underfunded and tragically understudied, and under researched and misunderstood,” Kate said. 

Over the years, Virginia has failed 12 drugs. Medical professionals say if an epilepsy patient fails two drugs, it’s unlikely that any others will work. She has seen several doctors in her home state of Virginia and across the country. Doctors have tried several things with her case and could never pinpoint where the seizures were coming from. 

Virginia’s mother refused to allow her disease to hinder her from living a full life and doing everything her siblings could do. Kate says Virginia has traveled with her family extensively. She’s gone paragliding in South Africa and swimming with manta rays in Hawaii. She ran cross country and is even on a competitive rock climbing team. All things they knew were a risk, but a risk they were willing to take.

“I would rather have a child with a broken arm than a broken spirit,” Kate said.

While searching Twitter in the fall of 2019, Kate came across Dr. Perry’s professional profile where he regularly posts about advancements in treatment for epilepsy. She decided to seek his opinion. After securing an appointment, mother and daughter flew to Texas. In her initial appointments, Dr. Perry ran tests to see Virginia’s seizures for himself. 

“From the beginning, it felt like a very collaborative relationship and a very transparent relationship, and that just stood out to me from other patient and caregiver experiences that we’ve had in the past,” Kate said. “I felt like everyone was familiar with her case history, everyone knew why we were there, everyone knew what we were hoping for. Again, not overpromising and not being overly optimistic, but really understanding our goals and what we had already tried." 

Virginia agrees that Cook Children’s was different from other appointments she’d been to. She was happy to finally have doctors that focused solely on her case.

“At Cook Children’s, they didn’t compare my case to anyone else, but looked at it as a singular case. I think that was the difference and they also had a more positive outlook. All of the doctors were good at explaining things in a way that I could understand them, but also not making me feel dumb,” Virginia said. 

After observations, running tests, and reviewing hundreds of pages of paperwork from Virginia’s doctors over the years, Dr. Perry was confident that he’d pinpointed where the seizures were coming from. He then recommended her for epilepsy surgery. Virginia was able to have her surgery and fly home two days later.

While visiting Cook Children’s, Kate and Virginia also met Cynthia Keator, M.D., medical director of the Epilepsy Monitoring Unit at Cook Children’s who made an impact on the Cooper family. Kate says the moment she met Dr. Keator, she felt immediately encouraged and appreciated how transparent she was about what she was seeing in Virginia.

Dr. Keator said she knew from the minute she saw the data on Virginia’s EEG that she could help her, and as a doctor that is always the best feeling.

“There is something about teenagers in general and just knowing that they’ve got the rest of their life ahead of them. You’re excited to get to their breakthrough and get them better, so they can start to have an independent life,” Dr. Keator said.

Since returning home, Virginia has gone back to school to complete her senior year and study for the ACT exam. While she was at Cook Children’s waiting for her surgery, she was excited to receive two college acceptance letters. She will soon apply for her top choice, McGill University, in Montreal where she hopes to attend next year. 

Virginia says it still hasn’t hit her that she’s had a surgery that could potentially change her life. She says the best part is the hope of having a normal college experience. 

“If it works, I don’t have to tell my professors about it, and my roommates, or my friends and have that complicate my whole experience too,” Virginia said.

Dr. Perry hopes the surgery was all Virginia needs to live a normal life and that her story is a testament to why epilepsy surgery should be considered more often. 

“People don’t pursue epilepsy surgery, despite it being the one thing we can do for epilepsy where we might be able to cure it and get you off of medication,” he said. “Epilepsy surgery is vastly underutilized.” 

Dr. Perry’s ultimate goal is for her to be seizure free, off of medication, and living happily ever after.

 Kate and Virginia both agree that having a support system while dealing with epilepsy is important. Having people who are there to listen with no judgement and willing to jump in when you need them most has been helpful to them both. 

“It’s really important to find one or two super close friends who you can talk through everything with and never feel insecure when talking to them,” Virginia said. “It really helps.”

As a mother who’s dealt with epilepsy for 16 years, Kate has three pieces of advice that she hopes will help other parents:

1. Build your support group. Seek out people who might be going through something similar and that you can lean on.

2. Take care of yourself. Do things for yourself and practice self-care.

3. Listen to your gut. Don’t be afraid to seek guidance from other physicians who specialize in your child’s disorder.

Virginia has one piece of advice for anyone dealing with epilepsy.

 “Never to doubt yourself. Just because sometimes your life is a little bit harder for you than for others doesn’t mean you can’t do the exact same things as they can or get as far as, or further in life.”

The first Texas dispensaries are now opening and selling their products to eligible patients across the state. But Texans who are interested in pursuing the so-called CBD oil treatment say there are several obstacles to getting the medicine.

There’s roughly 30 doctors across the state eligible to prescribe the medicine. Also, CBD oil is still federally illegal, so people have to pay out of pocket to secure it. And there are only three Texas dispensaries who can sell the medicine — two in Austin and one in Schulenburg.

In this video documentary, The Texas Tribune followed two families as they began their journey in pursuing medical cannabis treatment.

Full story here.

Compassionate Cultivation will be the first of the three licensed dispensaries to open in the state, but will be followed, in theory, by the other two companies that received licenses last year under the Texas Compassionate Use Act, which was passed in 2015.

Watch the story here. 

"I don’t know that she’s ever had a time where she’s been completely seizure-free," says her mother, Laci.Kadience has a genetic disorder called Tuberous Sclerosis, or "TS."

It affects about one in every 4,000 people, says Dr. M. Scott Perry of Cook Children's Medical Center. He says it affects almost every single organ system and often leads to debilitating seizures.

Read full story here.