Author’s Note: The name of the interviewee has been changed for privacy reasons.
Losing a child is never easy. Losing a child two days after birth to an unknown gene variant that leaves doctors baffled? The stuff of nightmares. And yet, that’s exactly what John and his family had to deal with.
In May 2016, John, a family-focused professional working in a strategic and innovation function within the healthcare space, was celebrating the birth of twin boys with his wife of six years and their young daughter. But there was an issue with one of John’s newborn sons.
“We first noticed something was wrong the morning after we brought him home from the hospital,” John said in an exclusive interview with Ranomics. “He seemed lethargic and a little different.”
What John, his family, and the doctors didn’t know, was that his newborn son had two variants in genes SCN2A and MYH7. These genes are responsible for the cell’s ability to generate and transmit electrical signals. Common variants in this gene have been found to increase the risk of developing cardiac arrhythmia, a hereditary heart condition that causes an irregular heartbeat and sudden infant death due to an interruption in the heart’s electrical signals. Its adult counterpart, Brugada syndrome, is a genetic disease characterised by abnormal electrocardiogram (ECG) findings and is the major cause of Sudden Unexplained Death Syndrome (SUDS), aka Sudden Adult Death Syndrome (SADS). Brugada was only discovered in 1986 and occurs primarily in males 35–40, with approximately five of every 10,000 people affected worldwide.
“We brought my son into the emergency room.The doctors were trying to resuscitate him, and at this point nothing was known about his genetic variants. My son died two days after he was born.”
Following his death, the OCME (Office of Chief Medical Examiner) conducted an autopsy. The regular string of tests were administered, but doctors couldn’t definitively connect any causal link to his death. More tests were then taken, including metabolic, structural, and genetic testing. Not many OCMEs do genetic testing because the technology for gene sequencing is not available to most medical examiner labs. The full autopsy took months.
“The [cardiology genetics group] helped us understand the possible link between the SCN10A gene variant, Brugada, and the cause of death,” John explained. “But again, nothing was definitive. We still don’t know how variants in this gene affect the electrical function of the heart, and there is still not a lot of definitive evidence. There is also debate on whether variants in this gene could be linked to Brugada syndrome. Since we learned about the genetic variants seven to eight months ago, no additional supporting evidence or correlations have been discovered.”
Frustrated by the lack of resolution and riddled with questions the doctors couldn’t answer, John began searching for answers himself. With an identical twin son potentially at risk, he couldn’t afford not to.
“I steeped myself in the topic of genetic variants, mutations, causes, and correlations, but was struggling to get any definitive answers.”
In late 2016, John met Ranomics Co-founder and CEO Cathy Tie at a healthcare innovation conference. Ranomics is a Toronto-based biotech startup that conducts proprietary research aimed at resolving Variants of Unknown Significance (VUS). The company is building the world’s first comprehensive knowledge base of functionally characterized genetic variants to help determine their role in disease development and treatment.
“What Cathy presented hit me right in the heart. She wanted to help parents find answers to previously unanswered questions about the death of their child. While Ranomics didn’t have the answers just yet, their mission was completely aligned with mine.”
According to Tie, the biggest problem facing hereditary disease testing is that more than 60 percent of all genetic tests are inconclusive. “This is due to newly identified genetic variants in the patient that have no clinical or medical precedence, leading to mis-or-non-diagnosis and compromising patient care.”
Tie’s goal is for Ranomics to “to eliminate unclassified genetic variants in all genetic tests. We believe that observing the functions of genetic mutations in clinically relevant model organisms is the closest model to understanding the genetic mutations in the human body. Interpretation of sequenced human genomes will not only hold the key to our understanding of individual health and well-being, but it will also unlock the next wave of personalized medicine.”
“If Ranomics could definitively link gene variants with disease, it would provide us with some answers about what caused the death of our son,” John said. “It would also help us better understand what precautions we can take with our living family members who have the same variant.”
John’s surviving son has regular appointments to check on his health. He currently has a regular ECG, a healthy echocardiogram, and isn’t displaying any signs of complications. John’s wife is not exhibiting any known health issues related to this condition, but John plans “to follow up regarding any connection with Brugada syndrome, which includes a procainamide challenge to determine if she actually displays any signs of Brugada in her ECG.”
“We did not have the opportunity to do anything about our son’s death. Had we known, perhaps there could have been steps we could have taken to save him.”
