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Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS)

Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a rare vascular disorder caused by a mutation in the actin alpha 2 gene (ACTA2) which encodes for a protein called alpha smooth muscle actin isotype 2. The disorder is most often caused by a heterozygous de novo mutation at p.Arg179His. This mutation is theorized to lead to disrupted actin polymerization, which in turn impairs the ability of smooth muscle cells to contract. Additionally, there is increased secretion of abnormal extracellular matrix which ultimately causes rigidity of muscular arteries and dilation of elastic arteries as well as aneurysms. Lastly, increased smooth muscle cell proliferation leads to thickening of the wall of large and small arteries and potentially obstruction of larger arteries.

Patients with MSMDS experience a wide array of clinical signs and symptoms. Most commonly, patients present with a congenital heart defect called patent ductus arteriosus, an inability to constrict the pupil known as congenital mydriasis, and cerebrovascular disease. Other congenital cardiovascular anomalies, aneurysms, prune-belly sequence, and intestinal malrotation are also common. Risk of mortality secondary to aneurysm, stroke, or pulmonary complications is high during childhood. To date, there is no definitive treatment for MSMDS. Currently, the Gray-Edwards lab is working on developing a pig model of MSMDS using a technique called base editing.

To contact us about MSMDS, please email Dr. Abby McElroy at abigail.mcelroy@umassmed.edu