SMDS patients overwhelmingly have pathogenic variants affecting ACTA2 R179, but a recent case was reported of a patient with SMDS and a miR-145-5p pathogenic variant.45 miR-145 represses expression of pluripotency markers like OCT4 and SOX2 to control smooth muscle cell fate.46, 47 This report therefore aligns with our hypothesis that incomplete differentiation of SMCs and retention of progenitor phenotypes underlies SMDS pathogenesis. This evidence concerns the gene SOX2 and spondylometaphyseal dysplasia, Sedaghatian type.