Rare Disease Day: Meet 4-year-old Carter, One of Many Patients Treated at Cook Children's for a Rare Disease

When Carter Halliburton’s family learned the cause of his seizures, a genetic disorder called SYNGAP1, only about 400 people in the world shared the same diagnosis.

A hurdle that came next was finding a neurologist who had firsthand knowledge of the condition. SYNGAP1 is not just medically complex but so rare that the specialists consulted initially couldn’t offer Carter much help or his parents much insight.

Challenges for 4-year-old Carter include many of the typical SYNGAP1 spectrum traits such as seizures, autism, impaired speech, intellectual disabilities and behavior problems. He receives care at Cook Children’s, a hub for research and clinical trials for rare types of epilepsy.

M. Scott Perry, M.D. head of Neurosciences and director of the Genetic Epilepsy Program at Cook Children’s, compares the study of rare diseases to finding a key that opens new pathways to treatment.

“Every rare disease has unique characteristics,” Dr. Perry said, “but they sometimes share related genetic malfunctions.”

On Rare Disease Day, Feb. 28, 2022, we want to share highlights of some groundbreaking work at Cook Children’s improving the quality of life for these patients.

Additionally, we’re featuring Carter to personify some of the unique struggles that rare diseases present. As Carter's dad Peter Halliburton puts it, life with SYNGAP1 has been “a rollercoaster ride.”

Despite SYNGAP1, Carter knows humor and happiness. He loves Mickey Mouse, his sensory swing, exploring the park and playing with his 2-year-old sister. Peter described new optimism for future medical breakthroughs. 

“As difficult as it is to have a child with this condition and so rare, we also feel really lucky that we have this diagnosis in the time period where you've got parents, researchers, doctors, biotechs and pharmaceuticals working collaboratively to bring these therapies to market in a timeframe that matters,” Peter said.

Connecting With an Online Community

From their home in McKinney, the Halliburtons soon found common ground online with SYNGAP1 families around the globe who post questions, answers, similar experiences, updates, support and passion for finding better treatments. They stay connected in a Facebook group, a Slack channel, Twitter and they're even taking on TikTok.

“It was really up to us to go and scour the internet and try to find a community out there that could give us more information,” Peter said.

Since Carter joined their ranks in 2019, the number of identified SYNGAP1 cases worldwide has since grown to about 1,000 thanks in part to the wider availability of genetic testing.

“Unlocking one disease may unlock others,” Dr. Perry said. “If we can develop a treatment that adjusts that genetic abnormality in one case, that same technology and idea could be applied to another rare disease to potentially correct that problem.”

Rare Disease Day is a time to honor patients and their advocates who raise awareness, money and industry interest on behalf of the lesser-known disorders.

What qualifies as a rare disease? Any disease that impacts fewer than 200,000 people, according to the definition used in the United States. The National Organization for Rare Disorders database lists roughly 1,200 entries. The National Institutes of Health says that collectively an estimated 25-30 million Americans are affected.

Dr. Perry gives credit to the persistent and resourceful parents who make phone calls, send emails, build coalitions, raise funds and attract attention to the rare diseases that impact their children.

“Rare disease parent advocates are very pushy folks in a very good way,” Dr. Perry said. “They’re dedicated to finding a solution and they know how to mobilize themselves very well, which is why I really enjoy working with them. They have a clear vision of what they want done, and they do great work.” 

Peter volunteers for the nonprofit SynGAP Research Fund in development and raising money for research, with more than $2 million in grants awarded by the organization. Their website features photos, videos and stories of children around the world. Blogs filled with tips and encouragement make this rare disease feel not quite so lonely. 

Making Strides in Treatment

Patients across Texas and from as far away as Washington and Massachusetts seek out epilepsy care at Cook Children’s. Dr. Perry explains that word gets out when rare-disease families go on social media to publicize their positive health care experiences.

“They want to cohort where they know there is expertise,” he said. “Another one will come. And another one will come. And then before you know it, you’ve got a big group.”

As medical director of the Genetic Epilepsy Clinic at Cook Children’s, Dr. Perry appreciates the sleuthing required to discover the root cause of a patient’s drug-resistant seizures. He studies the entire medical history for clues to identify patterns:

• seizure triggers
• age of onset
• associated medical conditions
• response to prior treatments
• imaging
• EEG results

“I see these kids with very difficult to control seizures, and I may spend hours looking over hundreds and hundreds of pages of records from throughout their life because you have to look at the story from the very beginning to where they are now,” he said. “Sometimes it’s not obvious in the beginning.” 

Tests can reveal the presence of a genetic variant, such as in SYNGAP1. Knowing the specific disorder allows a more targeted and effective treatment plan to be developed.

“As I tell families when we get a reason, whether I’ve got a treatment specific to it or not, at least now you know what to Google. You know what to keep looking for to see if something’s changed because you know exactly what your problem is,” Dr. Perry said.

Clinical trials and innovations underway at Cook Children’s involve several rare forms of epilepsy with some overlap in similarities.

Christos Papadelis, Ph.D., director of research at the Jane and John Justin Neurosciences Center, is primary investigator for a SYNGAP1 biomarker. Dr. Perry sits on a clinical advisory board for the SynGAP Research Fund. Cook Children’s has also taken a lead on these other rare epilepsies:  

• Dravet syndrome -- Cook Children’s treats more than 100 patients, considered a large population for this disorder. Cook Children’s also is a major contributor to clinical trials for drug development and new gene-based disease-modifying therapies. Cook Children’s will partner with the Dravet Syndrome Foundation for an upcoming conference in Fort Worth for Dravet families and providers this summer. 2022 DSF Conference - Dravet Syndrome Foundation (dravetfoundation.org)
• SCN8a encephalopathy -- Cook Children’s recently enrolled the first patient worldwide in a trial for therapy. Dr. Perry heads an international panel developing standards of diagnosis and treatment.
• CDKL5 disorder -- Cook Children’s participates in ongoing clinical trials for treatment.
• KCNT1 epilepsy -- Dr. Perry serves on the group’s board after KCNT1 parents reached out for help raising interest in the condition.
• Tuberous Sclerosis -- Dr. Perry serves on the group’s board.

Tactics to treat rare diseases continue to evolve as the knowledge about them improves. The Genetic Epilepsy Clinic at Cook Children’s added sleep medicine to its services last year. Dr. Perry also hopes to add psychology and psychiatry specialists who can address the behavioral issues that affect some people with epilepsy.

The Adult Genetic Epilepsy Clinic at Cook Children’s enables young patients to smoothly transition from pediatric care when they reach adulthood.   

Dr. Perry said the pharmaceutical industry is working to design medications specific to some of the rare disorders, holding the promise for a significant reduction in seizures. Another big benefit from early treatment is the potential to prevent intellectual disabilities or developmental delays from happening in the first place.

Dr. Perry pointed out that the science to fight rare diseases has taken huge strides in the last 10 years. He compares the rare disease diagnosis to running a marathon with the finish line in sight. “We know where we’re headed.”

Living with a Rare Disease

Lindsay and Peter Halliburton suspected something amiss before Carter’s first birthday. They noticed fluttering eye motion and the unexplained loss of muscle tone that caused him to collapse flat to the floor while crawling.

After various tests, the answer came when a genetics panel hit on a variant in the SYNGAP1 gene, which produces the protein SynGAP, responsible for regulating communication between neurons. This rare genetic mutation limits production of the critical protein in SYNGAP1 patients.

Carter was diagnosed at the age of 21 months with a condition he couldn’t outgrow or be cured of.  

“Googling it and seeing the prognosis was pretty devastating,” Peter said. “That little bit of hope that we have that things are going to normalize was out the window at that point.”

Seizures began to fire off in Carter’s brain circuitry as many as 100 times each day. Some were brief, eye flutter spasms; others were the loss of muscle tone in atonic drop seizures.  

“It's like a switch gets turned off in his brain. He falls to the floor. He'll hit his head if there's anything in his path on the way down,” Peter said.

Anti-seizure medications helped but caused side effects. So they kept tweaking the meds. Now, Carter experiences 12-15 seizures per day. 

Other aspects of SYNGAP1 create difficulties at home too. Carter can speak only a few words. He struggles with his gait and sleep. Silly and cuddly at times, he also reacts in outbursts of impulsivity and aggression.     

Attempts to find treatment sent the Hallilburtons as far as St. Louis, Houston and Austin in search of neurologists familiar with the rare disease. Peter eventually connected with Dr. Perry over Twitter, which led the family to Cook Children’s.

“He said, ‘You know, I've got a couple of other genes that are similar to SYNGAP that we're already working on. It would make sense for me to see more SYNGAP patients. And I would be interested in this,’” Peter recalled. “That's like a dream to have somebody at Dr. Perry's level reaching out to us.”

Since his son's diagnosis, Peter, self-taught in genetics, presented a caregiver’s perspective to a U.S. Congress panel over technologies advancing genetic therapies. He speaks enthusiastically about the SynGAP Research Fund’s efforts to identify more patients through testing and study of anonymized patient medical records.

The disorder is greatly underdiagnosed among people with autism and epilepsy, the coalition believes. Advocates are counting on a precision diagnosis that leads to precision treatment someday.

“If we had all sat back and just let things happen on their own -- instead of getting involved in funding, research and driving things like we have -- I think it would've been another few decades before we get to treatments for our kids,” said Peter, who sees clinical trials on the near horizon. “We're trying to accelerate that timeline."

“Our kids are the real pioneers,” he continued. “We're going to be potentially putting novel therapeutics in our kids, and there's some level of risk to that. But there's also massive upside potential for what their quality of life looks like if we can find a successful treatment.”

What advice does he offer for coping with a child’s rare disease? Take time to grieve.

“It's like a loss almost, when you first receive that diagnosis," he said. "I would say take time for yourself and then find your community. Go to social media and try to find other parents dealing with the same thing.”