SMAD4 and juvenile polyposis syndrome: Germline loss-of-function alterations involving one of two tumor suppressor genes playing a pivotal role in the transforming growth factor-β and bone morphogenetic protein (TGF-β/BMP) signal transduction pathway, namely bone morphogenetic protein receptor type 1A (BMPR1A) and SMAD family member 4 (SMAD4), are known to be a molecular pathogenic mechanism in JPS [5].