Supported by Mayo Clinic’s holistic, precision medicine approach, which included advanced genetic insights, access to an emerging therapy, and tailored treatment monitoring, Giana Urse gained the confidence and clarity she needed to pursue her dream of becoming a dog trainer.
Giana Urse, who lives with a rare form of genetic epilepsy, has always shared a rare connection with dogs. They seemed to gravitate toward her, says her mother, Nancy Musarra. At age 14, Giana earned the responsibility of getting her own dog, a Morkshire terrier named Bryan. Two years later, searching for independence after learning epilepsy would prevent her from driving, Giana welcomed a second dog, Joey, to her pack.
Joey eventually became Giana’s seizure-alert companion. Their deep bond not only kept Giana safe, it also ignited in her a dream of becoming a dog trainer. It was a goal that might have seemed unrealistic for someone navigating unpredictable seizures and developmental delays caused by the complex condition. But Giana made her own path, even in the face of limited school resources.
“My mom believed in me,” Giana says. “She is my assistant and helped me do the dog trainer program. Now I'm a dog trainer and help kids like me."
Giana’s perseverance in pursuing her dreams reflects a fortitude forged during a decades-long search for a diagnosis and treatment for the genetic condition known as KCNA2 epilepsy, which has shaped her life and development since infancy.
At the age of 19, Giana’s journey led her from her home in a suburb of Cleveland, Ohio, to Mayo Clinic, where she accessed the gene-targeted therapy 4-aminopyridine (4-AP). That treatment, coupled with a regimen of anti-seizure medications, helped to stabilize Giana’s cognitive function, organize her thought processes, and improve her ability to learn.
“When we went to Mayo Clinic and met Dr. (Lily) Wong-Kisiel, I felt like she listened to my perspective, which was just based on researching random articles because there wasn’t a lot of information available,” Nancy says. “I felt like all of the information I put together, she was able to help me sort through what was factual and what was hopeful. And I needed that.”
Moreover, Giana’s Mayo Clinic team focused on Giana’s needs and the precision testing required for her to safely begin the treatment.
“We had EKGs, EEGs, and then blood tests that tested the levels of the other medications she’s on and how the 4-AP might affect those,” Nancy says.
A long road to answers
For Nancy, who founded a patient advocacy and support group called the KCNA2 Epilepsy Global Connection when Giana received her genetic diagnosis, finding the correct diagnosis and an effective treatment was not always a certainty.
"Because there were so many different symptoms, I wondered, how could anybody untangle this?” Nancy says. "But at the time, my grandmother said to me, ‘Nancy, they are going to tell you, you will find out,’ and I believed her. But I didn’t realize how long it was going to last, and that was difficult.”
Giana was just 6 months old when she experienced her first tonic-clonic seizure. After the initial episode, the events occurred frequently but did not seem to follow a pattern. Giana’s Cleveland-based pediatric neurologists prescribed medication upon medication, and Giana cycled through 14 FDA-approved treatments before hitting upon a combination that kept the seizures under control.
When Giana was 7 years old, at the advice of her local neurology team in Cleveland, her parents submitted a sample of Giana’s blood and their own for genetic testing. A full twelve years passed before Giana’s blood sample tested positive for a de novo variation in the KCNA2 gene, which was the cause of the epilepsy.
Patients who have KCNA2 pathogenic variants have a spectrum of severity, says Giana’s pediatric neurologist, Lily Wong-Kisiel, M.D.
"Because there were so many different symptoms, I wondered, how could anybody untangle this?”
Nancy Musarra
The most common pathogenic variant of the condition, and the type that affects Giana, is a gain-of-function variant in the potassium channel. In patients with this gain-of-function pathogenic variant, dysregulation of neuronal excitability results in cells becoming hyperexcitable. Simplified, that hyperexcitability causes seizures and epilepsy.
"So many of these patients who have gain-of-function pathogenic mutation will have early-onset seizures in infancy and childhood,” Dr. Wong-Kisiel says. “Many of these patients, if they do not have epilepsy, often have cognitive delay with age; they often have ataxia and balance issues. On the flip side, patients with loss-of-function mutations tend to be less severe, but many of them still have seizures and developmental delay.”
For children with the condition, the ongoing neurologic interruptions throughout critical stages of brain development are detrimental.
"This is highly impactful in an early life period when you're supposed to be learning,” Dr. Wong-Kisiel says. “If you're unable to properly develop and learn and have a brain that's having intermittent or frequent seizures, that's a problem.”
Finding hope at Mayo Clinic
While a combination of anti-seizure medications did help to minimize Giana’s seizure activity, she continued to experience mental fogginess, memory issues, and processing delays. So in 2016, when Giana’s parents learned about the role of 4-AP in improving cognitive function, they knew they had to try the treatment.
“I read an article that said there was a treatment option and I'm like, ‘Oh my God, thank you!’” Nancy says. She immediately began researching how Giana might access the medication, but another two years passed before Nancy learned that physicians at Mayo Clinic were researching the efficacy of 4-AP in KCNA2 patients. Nancy reached out to Dr. Wong-Kisiel, who’d been treating another patient successfully with the drug, and an appointment for Giana was made.
Having run into numerous dead ends in their search for better treatment, Nancy says visiting Mayo Clinic in the summer of 2018 was a relief.
During Giana’s initial visit, a care team headed by Dr. Wong-Kisiel coalesced around her and developed a plan for Giana to begin receiving the treatment. Part of her initial exam included preliminary evaluations to establish whether she would be able to tolerate the 4-AP treatment. Included in that testing was baseline therapeutics testing to measure concentrations of the anti-seizure medications lamotrigine (Mayo ID: LAMO) and levetiracetam (Mayo ID: LEVE) that Giana was taking at the time.
Therapeutics testing, or therapeutic drug monitoring (TDM), is an essential component of a precision approach to epilepsy testing and care. Using TDM in tandem with diagnostic tests and pharmacogenomic (PGx) tests, which identify gene variants that impact a patient’s response to a medicine, enables patient-specific care.
“Precision epilepsy testing uses a combination of genetic and other tests to understand a person's specific genetic makeup and lead to optimized and personalized treatments,” says Paul Jannetto, Ph.D., vice chair of practice for clinical pathology in the Department of Laboratory Medicine and Pathology and co-director of the Clinical Mass Spectrometry Laboratory, where he oversees TDM. “This approach moves beyond the one-size-fits-all to identify the root cause of epilepsy, allowing doctors to choose treatments that are most likely to be effective.”
Three months after Giana’s first visit to Mayo Clinic, she returned as an inpatient to start 4-AP. Because of the drug’s potential side effects, continuous electroencephalogram (EEG) monitoring and electrocardiogram (EKG) testing were required to ensure Giana’s safety while the medication was titrated up to the appropriate level.
“It was a very comprehensive type of care,” Nancy says. “She was tethered to her bed, which was hard, but they came in with cards and a stationary bike, and they let us do art. It was a very safe experience. If I ever had a question, it was always answered, and the staff at Mayo made us as comfortable as we could be. I couldn’t have asked for anything more.”
During her inpatient stay, Giana also received therapeutic drug monitoring for her other medications.
“Having serial measurements that we do with TDM is crucial to make sure that we're maintaining those levels, because normal changes throughout a patient's lifetime can affect the medication concentrations and the dose needs to be constantly adjusted so they can maintain those therapeutic concentrations and be seizure-free,” Dr. Jannetto says. “Many patients often need to start taking additional medications for seizures or other conditions, and drug monitoring can help identify potential drug-drug interactions. Those results can help inform the patient's provider on any dose adjustments needed to maintain the therapeutic target, or if an alternate therapy might be needed.”
"Precision epilepsy testing uses a combination of genetic and other tests to understand a person's specific genetic makeup and lead to optimized and personalized treatments, this approach moves beyond the one-size-fits-all to identify the root cause of epilepsy, allowing doctors to choose treatments that are most likely to be effective.”
Paul Jannetto, Ph.D.
Precision epilepsy therapeutics
For people with epilepsy, achieving consistent seizure control often requires ongoing adjustment of therapy. Integrating pharmacogenomic insights with medication level monitoring enables a more personalized approach, helping clinicians refine treatment and evaluate response over time. This is especially important for patients with drug-resistant epilepsy, where optimal concentration ranges may fall outside standard thresholds. By providing deeper insight into how each patient responds to therapy, Mayo Clinic Laboratories supports more informed decisions and helps advance care across the epilepsy treatment journey.
Growing confidence: A future beyond diagnosis
Since adding 4-AP to her medication regimen, Giana has experienced myriad positive effects. Her success with the medication and its evolution to a more widely accepted treatment for KCNA2 epilepsy enabled Giana to transition her care closer to home.
“It helps her think more clearly, and her thinking is more organized,” Nancy says. “Her medication is better, and she has more spontaneous thoughts and she is able to learn more easily because she generally thinks more clearly.”
The treatment has also helped with her movement, says Dr. Wong-Kisiel.
“Her mobility and fluidity of speech has improved, and I think, in a sense, that has given her more confidence,” Dr. Wong-Kisiel says.
Indeed, it is that confidence that allowed Giana to advocate for becoming a dog trainer. It also played a part in Giana co-authoring a book called “The New Normal: 7 Things to Know as You Care for & Love a Child with Special Needs,” which describes the challenges and triumphs of parenting a child with special needs.
In the book, Nancy shares advice gathered from personal experience and hundreds of interviews with parents of children with special needs. It is advice, Nancy says, that is critical to stay hopeful when medical science has not yet caught up with one’s condition.
“One of the difficult things for parents (of children with KCNA2 epilepsy) is they worry a lot about the future,” Nancy says. “And what I like to say to them is that your child has many strengths, and to focus on those strengths. Believe in your child. I believed in Giana. She wanted to be a dog trainer, and she is a dog trainer. Is she the same as every other dog trainer? Nope. So we’re unique, and we take it as a strength.”
Learn more about Mayo Clinic Laboratories’ precision epilepsy therapeutic testing.
