Taken together, HHT1 and HHT2 account for more than 80% of all HHT cases, whereas a small number of patients show mutations in SMAD4 (MADH4) or in BMP9 gene (GDF2), which are responsible for less common HHT variants such as a combined syndrome with juvenile polyposis (JP-HHT) and HHT5, respectively (28, 29). This evidence concerns the gene GDF2 and juvenile polyposis syndrome.