Heritable Thoracic Aortic Diseases in Pediatric Practice: From Molecular Mechanisms to Genotype-Informed Management,...

Background: Heritable thoracic aortic disease (HTAD) encompass a heterogeneous spectrum of conditions characterized by increased susceptibility to developing thoracic aortic aneurysm and life-threatening complications, including aortic dissection and rupture. Despite distinct underlying mechanisms involving extracellular matrix integrity, vascular smooth muscle cell function, and dysregulation of signaling pathways, these disorders converge on a shared vulnerability of the aortic wall. Although acute events typically occur in adulthood, the disease process often begins early in life, making HTAD highly relevant in pediatric practice, where early recognition and longitudinal management are essential. Aims: This narrative review provides a biology- and genetics-oriented, translational complement to current consensus recommendations, framing pediatric HTAD as a developmentally shaped disorder of the aortic wall in which genotype increasingly informs diagnosis, surveillance, and treatment. Methods: Relevant studies were identified through a comprehensive PubMed search, with particular focus on pathogenic mechanisms, current clinical guidelines, follow-up strategies and emerging genetic perspectives. Results: Genetic testing is emerging as a key tool for the management of HTAD, although its clinical utility remains limited by provisional genotype-phenotype correlations and inconclusive results. Current risk stratification is still mainly based on aortic diameter surveillance, while pharmacological strategies are predominantly extrapolated from Marfan syndrome trials, highlighting important gaps in evidence. Conclusions: Genetic advances are expanding management opportunities in HTAD, but their clinical translation remains challenging. Disease-specific risk models integrating genetic and clinical data may improve individualized risk stratification, treatment strategies and clinical outcomes.