Aortic and vascular disorders [80 genes]

Aortopathies are diseases whose main manifestation (which is determinant for patient prognosis) is arterial disease, with the aorta being the most commonly affected artery. They can occur within the context of syndromic diseases (such as Marfan, Ehlers-Danlos, Loeys-Dietz, and Shprintzen-Goldberg syndromes, among others) and non-syndromic diseases (familial thoracic aortic aneurysm and/or dissection, or TAAD). Even within the first group, often the only evident clinical manifestation is an aortic or vascular event.

Most of these diseases follow an autosomal dominant pattern, with a significant percentage of sporadic cases due to a de novo variant. Penetrance and clinical expressivity, including age of onset of the disease, degree of dilatation, and location along the arterial tree depend on the specific genetic basis (affected gene and type and location of the detected variant).

The prevalence of Marfan syndrome is 1:3,300 to 1:20,000, while the prevalence of familial thoracic aortic aneurysm and/or dissection in adults ranges between 1:5,000 and 1:4,000,000.

Genetic testing in aortopathies enables:

• Diagnostic confirmation, which—especially in this group of diseases—often determines management, follow-up, and multidisciplinary study. Surgical thresholds for aortopathies depend on the specific genetic cause for each case.
• A more accurate study of the patient’s relatives in order to provide carriers with an early/preclinical diagnosis, while non-carriers can safely be discharged from cardiological follow-up. This has proven to be a cost-effective strategy for this disease.
• An approach to prognosis for each specific patient based on the type of gene affected and the type of genetic variant identified. Our scientific team has pioneered this type of genotype-phenotype correlation analysis.

In patients with aortopathies whose findings are suggestive of a familial or genetic clinical picture (onset before age 60, coexistence of intracranial aneurysms, phenotypic features suggestive of syndromic aortopathies, or family history of aortopathy and/or sudden death), genetic testing is recommended according to current guidelines (PMID: 36322642).

The probability of identifying a variant associated with familial thoracic aortic aneurysms and dissections depends on how distinct the clinical manifestations of the disease are, on the clinical picture, and on the suspected syndrome. It can reach values over 90%-95% in cases with Marfan syndrome, while it is lower for other etiologies such as familial thoracic aortic aneurysms and dissections.