After a genetic defect took the life of her father at age 35 and her brothers at ages 23 and 18, Arizona teenager Zowie Claudio knew she was living with a time bomb in her chest. She inherited a weakness in the thoracic aorta, which carries blood from the heart to the rest of the body. The defect could cause her aorta to rupture without warning.
Armed with that knowledge, thanks to the pioneering research of geneticist Dianna M. Milewicz, MD, PhD, the young woman recently traveled to Houston for preventive surgery to repair the weakened artery.
For more than two decades, Milewicz, the President George Bush Chair in Cardiovascular Medicine at The University of Texas Health Science Center at Houston (UTHealth) and a member of UT Physicians, has been discovering genetic defects linked to the familial form of thoracic aortic disease.
Milewicz was contacted by a member of Zowie’s family in 2005 following the death of Zowie’s father David Claudio at the age of 35.
“My husband’s sister Abby Kohn reached out to Dr. Milewicz for help and we’re glad she did,” Zowie’s mother Angela Claudio said. “Back then, the genetic mutation linking my husband and children had not been discovered.”
Zowie is the sole sibling alive following the death of her older brother Jayce at age 23 in 2010 and her younger brother Seth at age 18 in 2018. Zowie’s father and brothers all had aortic dissections.
A weakness in the wall of the thoracic aorta can leading to a ballooning, called an aneurysm, which can dissect, or tear. Thoracic aortic disease, specifically thoracic aortic aneurysms leading to dissections, is the cause of death for an estimated 15,000 to 20,000 Americans each year.
The first time many people heard of the disease was in 2003 when Hollywood actor and “Three’s Company” star John Ritter died from it. Milewicz leads the John Ritter Research Program in Aortic and Vascular Diseases at UTHealth, which focuses on preventing premature deaths due to thoracic aortic disease by improving diagnosis, treatment, and public awareness of this disease. It was established through a collaboration between UTHealth and John Ritter’s widow, Amy Yasbeck, and other members of the Ritter family.
A genetic analysis of Zowie’s blood revealed she had a mutation in a gene named PRKG1 that impairs the muscle cells in the wall of the aorta.
“The mutation causes the protein to always be active. It is almost like the brakes on your car have gone out and there is no way to stop it,” Milewicz said.
Zowie, 16, and her mother traveled from Chandler, Arizona, for the surgery after careful monitoring revealed that her thoracic aortic aneurysm had reached a size that required surgery.
“We needed to do something,” Angela said. “We couldn’t just hope that everything would be all right.”
Her surgeon Anthony Estrera, MD, professor and ad interim chair of the Department of Cardiothoracic and Vascular Surgery at McGovern Medical School at UTHealth, performed a procedure known as a valve-sparing aortic root replacement at the Aortic Center of Excellence at Memorial Hermann Heart & Vascular Institute-Texas Medical Center.
“The benefit of this procedure is that we were able to preserve her native aortic valve so she won’t have to take anticoagulant drugs for the rest of her life,” Estrera said.
During the surgery, Estrera rerouted the flow of blood away from the aorta, detached it from the heart, replaced the weakened tissue in the aorta with a graft, and reattached it to the heart.
“We reduced her risk of death from sudden aorta rupture,” said Estrera, the Hazim J. Safi, MD, Distinguished Chair in Cardiothoracic and Vascular Surgery at UTHealth and a member of UT Physicians. “She can move on with her life.”
Less than a month after the procedure, Zowie was back at Campo Verde High School and able to rejoin her yoga classes.
Milewicz and her team of researchers have discovered nine of the genes that are now known to cause a predisposition for thoracic aortic aneurysms and dissections, and are using their expertise to inform gene-based clinical management and treatment of aortic diseases. Milewicz is also on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.
Angela said the family is happy to participate in the genetic research being conducted by Milewicz and believes it will help identify others at risk for this life-threatening condition. “This is very important research because often there are no symptoms,” she said.
“I would have lost all three of my children if it were not for Dr. Milewicz,” she said.