SMAD4 and hereditary hemorrhagic telangiectasia: Most individuals meeting the clinical diagnostic criteria for HHT harbor pathogenic variants in four TGFb pathway genes: Endoglin (ENG), Activin Receptor-Like 1 (ACVRL1 or ALK1), SMAD family member 4 (SMAD4), and Growth Differentiation Factor 2 (GDF2 or BMP9)] [130].