This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy.
Mutations in the ACTA2 gene lead to a multisystemic smooth muscle dysfunction syndrome that causes vascular disease, congenital mydriasis, and variable presentation of urinary and gastrointestinal problems.
Further combined analysis of ACTA2 and other, possibly causative, genes in larger cohorts of MMD and other vascular diseases may identify possible common disease-causing mechanisms.
We also present the current evidence that both NF1 and ACTA2 mutations promote increased smooth muscle cell proliferation in vitro and in vivo, which leads us to propose that these diffuse and diverse vascular diseases are the outward signs of a more fundamental disease: a hyperplastic vasculomyopathy.
Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD.