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]. The gene discussed is SMAD4; the disease is hereditary hemorrhagic telangiectasia.