What is ACTA2?

Mutations in the ACTA2 gene are associated with loss of smooth muscle contractility. Smooth muscle cells form part of the wall of most vessels in the body, the lungs, the gastrointestinal system, the bladder and the eye among other organs.  Mutations in the ACTA2 gene lead to abnormal production of alpha smooth muscle actin isotype 2, a protein that forms part of the scaffolding of the contractile (shrinking) system of smooth muscle cells.

 

Multiple variations of ACTA2 mutations exist, and the ACTA2 gene has been implicated in multiple diseases to include Familial Thoracic Aortic Aneurysm and Dissection (TAAD), Abdominal Aortic Aneurysm and Dissection (AAAD), Ischemic Strokes, Premature Coronary Artery Disease, and most recently Multisystemic Smooth Muscle Dysfunction (ACTA2.R179H predominantly). Over 30 ACTA2 gene mutations have been identified as contributors to thoracic aortic aneurysm and dissection (see Table 1).

Resources

Monitoring and Guidelines for Patients with ACTA2 (Based on Genet Med. 2018 Jan 4. doi: 10.1038/gim.2017.245. [Epub ahead of print])

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

  • A baseline brain MRI and head and neck MRA should be performed at initial genetic diagnosis to evaluate the burden of white matter injury, ischemic– hypoperfusive events, and degree of stenosis, and to determine future risk of stroke and management to prevent neurologic complications.
  • Although disease progression and optimal screening intervals have not been established, periodic screening for cerebrovascular disease should be considered as part of the patient’ s surveillance.
  • Patients who have seizures should be managed with standard anticonvulsant therapy.
  • Treatment with aspirin may be considered in asymptomatic patients with evidence of cerebral vasculopathy for the prevention of a first stroke.
  • Patients who had prior aortic root repair with mechanical valve replacement or thromboembolic events should be monitored and sufficiently anticoagulated.
  • Patients, especially young children, should be closely monitored during illness resulting in low oxygen saturation and acute infections with fever increasing cerebral metabolic demand. Any sudden change in neurologic function should be urgently evaluated.
  • Complete eye examination by an ophthalmologist should be considered to assess vision and the need for glasses.
  • Funduscopic examination should be considered to assess arterial tortuosity and evolving complications.