Within days of her birth, Amelia Terven began experiencing ever-increasing numbers of seizures. They left her so exhausted that she would fall asleep when they ended, only to be awakened a short time later by another seizure.
By the time her desperate parents made contact with Lurie Children’s nationally-renowned Epilepsy Center, Amelia had already been treated unsuccessfully by two pediatric neurologists. They spoke with Lurie Children’s pediatric neurologist and epilepsy specialist John J. Millichap, MD.
“Dr. Millichap asked us a lot of questions about Amelia’s seizures,” says her mother, Michelle. “Then he said, ‘Can you get here tomorrow?’ and we said, ‘Yes!’”
Dr. Millichap suspected Amelia had a rare form of early life epilepsy caused by a non-inherited mutation of the KCNQ2 gene – a gene that is a major focus of his research work. The gene is involved in the proper functioning of a potassium channel in the brain, and mutations in it are associated with seizures.
During the family’s drive from their home in Springfield, 5-week-old Amelia had 25 seizures. Within hours of being admitted, Dr. Millichap started her on a medication that research had proven to be effective for her type of epilepsy. By that evening, Amelia’s seizures had stopped.
Now age 2, she has remained seizure-free, and receives early intervention services for developmental delays.
“She loves to cuddle and give us hugs,” says Amelia’s father, Rick. “That would not have been possible if she was still having 25 seizures a day.”
Lurie Children’s Division of Epilepsy treats nearly 2,200 children each year, making it one of the busiest centers in the Midwest.
Epilepsy is one of the first programs in Lurie Children’s Precision Medicine Initiative. Precision medicine combines everything currently known about a specific disease with everything currently known about an individual child, including their genetic code. This revolutionary approach allows caregivers to tailor the treatment to the child, eliminating much of the guesswork. This is key in epilepsy, where uncontrolled seizures can result in impaired brain development, the inability to walk and talk and cause early death.
According to Dr. Millichap, the KCNQ2 gene has more than 100 mutations that can cause seizures. Through genetic testing, Amelia was found to have a previously unknown mutation.
“KCNQ2 is a known target for anti-seizure drugs,” says Dr. Millichap. “Understanding this gene and understanding Amelia will help us to develop drugs not only for children with early life epilepsy, but also for people with adult epilepsy, traumatic brain injury and strokes.”
Amelia is one of several Lurie Children’s patients with early onset epilepsy enrolled in a collaborative clinical trial with Dr. Millichap, Epilepsy Center Medical Director Linda Laux, MD, and colleagues at Northwestern University Feinberg School of Medicine’s Institute for Translational Neuroscience, led by Dr. Alfred L. George, Jr., MD. The George lab uses an automated ion channel drug screening platform, one of only a few available in the U.S., to determine the functional consequences of mutations in sodium or potassium ion channel genes associated with epilepsy, including KCNQ2. This technology speeds up the drug identification process significantly — from months to weeks.
For each ion channel mutation identified from a patient, a functional and pharmacological profile is created using automated electrophysiological recordings. First, the investigators determine the effect of the gene mutation on the channel’s behavior, usually too much activity or too little. Then, they screen many different FDA-approved antiepileptic and related drugs for each mutation to determine which ones bring the channel’s activity back to or as close to normal as possible. They also can identify drugs that make the channel’s functioning worse. The results will enable epilepsy specialists to select the most effective drug based on the patient’s precise genetic mutation.
The Precision Medicine Epilepsy program is co-led by Anne Berg, PhD, a research professor at the Stanley Manne Children’s Research Institute at Lurie Children’s, and Leon Epstein, MD, Head of the Division of Pediatric Neurology.
Dr. Berg was the lead author of a 2018 study published in JAMA Pediatrics that recommended using routine genetic sequencing testing as the first-line clinical method for diagnosing young children with seizures.
In the study, which focused on children under the age of 3, specific genetic factors were found to be the cause of epilepsy in 40 percent of patients evaluated for first presentation with seizures. Berg says that chromosome microarray tests – which are the current standard for diagnosing seizures — are effective less than 10 percent of the time in diagnosing this same population.
“Imagine checking for errors in a child’s DNA as proofreading a book,” says Dr. Berg. “Chromosome microarray tests can detect whether entire chapters are missing, but genetic sequencing technology can detect tiny spelling errors in that DNA. And one tiny mistake can have a devastating impact on a child. This genetic information may also help identify which drugs might help and also which drugs to avoid. Our recommendation could be a game-changer in epilepsy diagnosis, and make precision medicine part of standard clinical practice.”
Amelia’s progress continues to be closely monitored by Dr. Millichap. Her parents say they are heartened that their daughter is cared for by a team that is so research-focused.
“If Amelia’s genetic information can help others like her, it would be wonderful,” says Michelle.
Lurie Children’s Precision Medicine Epilepsy program is supported by Tina and Joe Wolf, the Cunneen Family, the Jack Pribaz Foundation and the Pediatric Epilepsy Research Foundation.