Beyond the Aorta: Extra-Aortic Vascular Disease and Screening in Heritable and Systemic Arteriopathies

Heritable thoracic aortic disease (HTAD) comprises genetic disorders that predispose to thoracic aortic aneurysm and dissection. Several also affect arteries beyond the aorta. This narrative review examines the burden, distribution, mechanisms, and screening implications of extra-aortic vascular disease in vascular Ehlers–Danlos syndrome (vEDS), Loeys–Dietz syndrome (LDS), Marfan syndrome (MFS), and nonsyndromic HTAD, alongside the related systemic arteriopathies spontaneous coronary artery dissection (SCAD) and fibromuscular dysplasia (FMD). Disease- and genotype-specific patterns emerge, although estimates differ with referral patterns, imaging coverage, and outcome definitions. In the Montalcino Aortic Consortium (MAC), COL3A1 carriers had the highest proportion of extra-aortic clinical arterial events, with prominent abdominopelvic and cervical involvement. LDS showed widespread arterial disease and head and neck involvement. MFS had fewer clinical arterial events, but imaging studies identified branch aneurysms, particularly in patients with advanced aortic disease. SCAD and FMD frequently involved additional vascular territories. Findings from broader nonsyndromic thoracic aortic disease cohorts should be distinguished from genetically confirmed HTAD. Imaging-detected aneurysm prevalence and clinical event proportions are not interchangeable. Guidelines and consensus support disease-specific vascular assessment, but anatomical coverage, surveillance intervals, and evidence strength vary. Comprehensive baseline imaging is supported in LDS, FMD, and SCAD; European guidance also recommends peripheral surveillance in vEDS and MFS. Additional assessment in nonsyndromic HTAD and cervical artery dissection depends on genotype and clinical features. We outline a practical framework integrating the presenting vascular lesion, molecular diagnosis, prior events, family history, and imaging-related burden, and discuss when an extra-aortic presentation should prompt aortic evaluation. Prospective studies are needed to establish whether increased detection and changes in management improve patient-important outcomes.