SMAD4 and hereditary hemorrhagic telangiectasia: In addition, a mutation of the SMAD4 gene on chromosome 18 (tumor suppressor gene that mediates TGF-beta) is associated with a combination syndrome involving both juvenile polyposis and hereditary hemorrhagic telangiectasia, seen in approximately 1–2% of tested patients (Faughnan et al. 2011; Brinjikji et al. 2017a; Trerotola and Pyeritz 2010).