Late onset ACTA2 variants

ACTA2 mutations, affecting positions different from Arg179, are generally associated with predominantly vascular disease, often with a later or more variable presentation. 


These variants most commonly affect the aorta and major blood vessels and are part of the spectrum of heritable thoracic aortic disease.

Clinical manifestations of ACTA2 variants:

In contrast to MSMDS, these variants typically do not involve widespread multisystem smooth muscle dysfunction and are less likely to present with congenital features such as fixed dilated pupils. The most common presentations are:



  • Thoracic aortic aneurysm and dissection (FTAAD)
  • Disease involving the aortic root and ascending aorta
  • Early-onset vascular disease
  • In some cases, occlusive vascular disease


ACTA2: A diverse spectrum of disease

Although these variants often present later in life, disease severity can vary significantly, even within the same family. Importantly, aortic complications such as dissection may occur at relatively small aortic diameters, which has implications for monitoring and clinical management.



Cerebrovascular involvement can also occur in some individuals, including Moyamoya-like arteriopathy. For example, certain variants such as Arg198Cys have been associated with combined aortic disease and cerebral vascular abnormalities, illustrating the variability within ACTA2-related conditions.



Notes: 

  1. 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. Developed by the task force on the management of peripheral arterial and aortic diseases of the European Society of Cardiology (ESC). Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), and the European Society of Vascular Medicine (ESVM) https://doi.org/10.1093/eurheartj/ehae179