De novo ACTA2 variants disrupting arginine 179 to any of six amino acids lead to Smooth Muscle Dysfunction Syndrome (SMDS), a childhood-onset condition characterized by the earliest onset of MMD-like cerebrovascular disease and thoracic aortic disease, along with patent ductus arteriosus, pulmonary hypertension, aberrant lung development, fixed dilated pupils, gut malrotation, hypoperistalsis, and hypotonic bladder8,11,12. This evidence concerns the gene ACTA2 and multiminicore myopathy.