ISCHEMIC STROKE

• ACTA2 angiopathy is a vascular disease resulting from either occluded or enlarged arteries and can be caused by mutations in a single gene
• the vascular smooth muscle cell-specific isoform of α-actin (ACTA2) is a significant component of the contractile apparatus throughout the arterial system (Guo, 2009)
• heterozygous ACTA2 mutations can cause the inappropriate proliferation of SMCs ⇒ this may represent another pathogenetic pathway contributing to occlusive vascular disease
• most cases are diagnosed in childhood and present with:
  • familial thoracic aortic aneurysms and dissections (TAAD)
  • premature onset of coronary artery disease (CAD)
  • premature ischemic strokes (including moyamoya angiopathy)
• in addition to the recommended routine imaging of the aorta for aneurysms, ACTA2-mutation carriers should also be monitored for CAD and cerebrovascular occlusive disease

• SMCs and myofibroblasts from affected individuals proliferate more rapidly in culture than control cells ⇒  increased SMCs proliferation leads to steno-occlusive disease
• not all regions are affected; it is hypothesized that SMC proliferation depends on the presence of the mutation and an additional factor (vascular injury or increased biomechanical stress)

• aortic disease
  • thoracic aortic aneurysm and dissection in childhood and young adulthood
  • patent ductus arteriosus
• cerebrovascular disease
  • ischemic strokes/TIA
  • seizures
• pulmonary arterial hypertension
• peripheral arterial aneurysms
• GI abnormalities
  • intestinal malrotation
  • gastroesophageal reflux (GER)
  • constipation

• large vessel atherosclerosis
• vasculitis
• other genetic vascular diseases (e.g., Grange syndrome)
• connective tissue disorders
• sickle cell disease