The natural history of a family with aortic dissection associated with a novel ACTA2 variant

Disease-causing heterozygous variants in the ACTA2 gene cause an autosomal dominant heritable thoracic aortic disease (HTAD) with thoracic aortic aneurysm and dissection as main phenotype, and occasional extravascular abnormalities such as livedo reticularis. ACTA2-HTAD accounts for an important part of non-syndromic HTAD, with detection rates varying between 1.5-21% according to different studies. A consensus statement for the screening and management of patients with pathogenic ACTA2 variants has been recently published by the European reference network for rare vascular diseases (VASCERN). However, management of ACTA2 patients is often challenged by extremely variable inter- and intra-familial clinical courses of the disease. Here we report a family harboring a disease-causing ACTA2 variant. The proband and two siblings presented with acute type A aortic dissection and rupture involving nondilated aortic segments before the age of 30. Their mother died at 49 years-old from type B aortic dissection and rupture. Genetic testing revealed the heterozygous novel p.(Pro335Arg) variant in the ACTA2 gene in the proband and in the affected siblings. The clinical history of this family highlights the difficulty of adopting effective prevention strategies in ACTA2 patients.

Automated summary

Heterozygous variants in the ACTA2 gene can cause HTAD, with thoracic aortic aneurysm and dissection as main phenotypes, and detection rates varying between 1.5-21%. A consensus statement for screening and management of patients with pathogenic ACTA2 variants has been published by the European reference network for rare vascular diseases (VASCERN). However, the extremely variable clinical courses of ACTA2 patients within and between families pose challenges for effective prevention strategies.