ACTA2 and spondylometaphyseal dysplasia, Sedaghatian type: ACTA2 variants impairing Arg179 are associated with a particularly severe but also distinctive multisystemic phenotype summarized as syndrome of multisystemic smooth muscle dysfunction (SMDS) that exhibits congenital mydriasis, intestinal hypoperistalsis, hypotonic bladder, pulmonary hypertension, aortic disease and Moyamoya-like cerebral arteriopathy [2–4].