Moreover, studies using KRIT1 or CCM2 deficient cell or animal models have shown highly similar phenotypes (28), but loss of CCM3 causes more severe and acute CCM development both in animal models and human patients (29, 30), suggesting that the pathophysiology and progression of CCM lesion development is a complex process that is influenced by the specific gene affected. This evidence concerns the gene CCM2 and cerebral cavernous malformation.