After the birth of identical twins John and Warren Stone, their parents Mary Elizabeth and Meade Stone were confronted with a medical crisis when both boys began experiencing frequent seizures. Initial tests, including an epilepsy panel, failed to identify the cause, leading doctors to suspect a genetic origin but leaving the family without a clear diagnosis. “When you’re struggling with the fact that things aren’t going as expected, it adds to the suffering when you can’t put a name to the problem or wrap your mind around it,” said Mary Elizabeth Stone.
Tragedy struck when Warren died at 19 days old due to a medical error. The Stones continued searching for answers for John, eventually connecting with Pankaj Agrawal, M.D., MMSc, chief of neonatology at the University of Miami Miller School of Medicine’s Department of Pediatrics and physician-in-chief at Holtz Children’s Hospital.
Dr. Agrawal leads research into rare pediatric diseases—conditions affecting fewer than 200,000 Americans—and is establishing the Center for Orphan Disease (CODe) at UHealth. While each rare disease is uncommon individually, about 25-30 million Americans are affected by such conditions overall.
“Parents desperate for answers turn to Dr. Agrawal’s laboratory as a last hope for a diagnosis,” according to information provided in the release. Dr. Agrawal stated: “We’re trying to understand the underlying mechanism of a disease. Without knowing the genetic cause, we can never find treatments.”
The team uses whole-genome sequencing as an initial step to search for mutations across all genes rather than just targeted panels. They supplement this approach with RNA sequencing, protein studies, and cellular or animal models if necessary.
The Stone twins were ultimately diagnosed with Ohtahara syndrome—a seizure disorder—linked to mutations in the SCN2A gene after research by Dr. Agrawal’s team. This gene had not previously been associated with this specific condition but is now included in epilepsy screening panels.
Dr. Agrawal explained that his group has identified more than 50 novel genes through their work: “We often identify a completely new condition caused by a gene that hasn’t been linked to a human disease previously.” His team collaborates internationally and continues investigations even when immediate answers are elusive.
For families worldwide who reach out from locations such as Israel and Uruguay, having any diagnosis provides relief—even if treatment options are limited or unavailable at present. “Once you see the benefits the families experience from this approach, it just feels so special that your work is making a real difference,” said Dr. Agrawal.
Recent advances include using customized gene-editing therapies like CRISPR on individual patients’ mutations—demonstrating potential pathways toward future treatments where none exist today.
Having received their sons’ diagnosis allowed the Stones peace of mind regarding future pregnancies and enabled better-informed care decisions for John during his life until he passed away at age 14 due to complications from his condition.
Mary Elizabeth Stone encouraged other parents facing similar uncertainty: “I’ve seen a lot happen in John’s lifetime. It wasn’t the right timing for him for a cure, but he and his brother have been a part of this scientific advancement that continues.” She added: “I’m proud to know their hardships weren’t in vain. These talented and compassionate doctors were able to figure out their diagnosis so that it can be used to help other affected individuals going forward.”
