The CM-AVM syndrome is caused by germline or inherited LOF variants in two genes, RAS P21 protein activator 1 (RASA1) (178, 179) and ephrin receptor B4 (EPHB4) (180), accompanied by an additional somatic variant acting as a second hit (181). This evidence concerns the gene RASA1 and capillary malformation-arteriovenous malformation syndrome.