First, we performed manual analysis and variant calling of the sequencing data for the genes known to cause HHT (ACVRL1, ENG, GDF2, SMAD4) or vascular malformation syndromes with similar phenotypes (EPHB4, RASA1), as well as PIK3CA, which has been shown to modify vascular malformation phenotypes [17]. This evidence concerns the gene EPHB4 and hereditary hemorrhagic telangiectasia.