This result is in accordance with the recent identification of a bi-allelic loss of ALK1 or ENG in at least 50% of tested cutaneous telangiectasia samples isolated from HHT patients [35], supporting the hypothesis that a second ‘knudsonian’ somatic hit in the other allele is necessary to drive HHT pathogenesis. This evidence concerns the gene ACVRL1 and Telangiectasia.