We analyze the role of genes involved in vascular smooth muscle cell contractility (<i>ACTA2</i>, <i>MYH11</i>), TGF-β signaling, and DNA repair mechanisms that drive MMS, alongside the genetic basis of syndromic forms associated with neurofibromatosis type 1, trisomy 21, and RASopathies. Here, ACTA2 is linked to neurofibromatosis type 1.