MAP3K3 and cutaneous mastocytosis: The pathogenesis of CM has been recognized in animal models of cavernomatosis as a multi-hit process requiring loss-of-function events in CCM genes (vascular suppressor genes that constrain vessel growth), along with gain-of-function events in PIK3CA, which acts as a vessel ‘oncogene.’12 Although CCM loss-of-function genes are found in >90% of familial CM, this is not the case in sporadic CM where PIK3CA or MAP3K3 mutations alone are sufficient to trigger CM formation.30,46 Here, we confirm that somatic mutations in CCM genes are not required to trigger CM in children.