PRKG1 pathogenic variants cause thoracic aortic dissection with minimal aortic dilation: Insights from the UTHealth Houston multidisciplinary aortic and vascular disease conference.

A single, recurrent, gain-of-function pathogenic variant in PRKG1 (p.Arg177Gln, also referred to as p.Arg192Gln) causes heritable thoracic aortic disease with a high lifetime risk for aortic dissections that frequently occur before there is enlargement of the proximal thoracic aorta. This report summarizes the clinical manifestations of the PRKG1 pathogenic variant in two unrelated families, including early-onset type A dissection, chronic thoracoabdominal dissection with visceral complications, and elective aortic repair of the proximal aorta with minimal enlargement. In both families, multiple individuals experienced acute dissections at young ages that led to five fatalities. These cases illustrate the early onset of manifestations of PRKG1-related disease, which are primarily dissections, and underscore the essential role of aggressive gene-based management to prevent dissection in these cases.