Pathophysiology
Clinical meaning
The clinician managing TAA must understand the genetics of heritable thoracic aortic disease, evidence-based surgical thresholds, and long-term post-surgical surveillance. Heritable thoracic aortic disease (HTAD) accounts for approximately 20% of all TAAs and has specific clinical implications. Marfan syndrome (FBN1 mutation, prevalence 1:5000): fibrillin-1 deficiency causes increased TGF-beta signaling leading to aortic root dilation (80% of patients), lens subluxation, skeletal manifestations (tall stature, arachnodactyly, pectus deformity), and dural ectasia. Loeys-Dietz syndrome (TGFBR1/2, SMAD3, TGFB2/3 mutations): aggressive arterial disease with aneurysms throughout the arterial tree, arterial tortuosity, hypertelorism, bifid uvula, skin translucency; surgical threshold is lower (4.0-4.5 cm) due to higher rupture/dissection risk at smaller sizes. Vascular Ehlers-Danlos (vEDS, COL3A1 mutation): type III collagen deficiency causing extreme arterial fragility; spontaneous arterial rupture, bowel perforation, organ rupture; surgical intervention carries very high complication risk; avoid invasive vascular procedures when possible. Familial thoracic aortic aneurysm/dissection (FTAAD, ACTA2, MYH11 mutations): autosomal dominant without systemic features; ACTA2 mutations associated with early-onset stroke, coronary disease, livedo reticularis, and iris flocculi. The clinician coordinates genetic testing and counseling, applies genotype-specific surgical thresholds, and manages long-term surveillance.