Familial forms of CCM occur at three known genetic loci. The gene for CCM1 encodes KRIT1 (krev interaction trapped 1), and has been found to bind to ICAP1alpha (integrin cytoplasmic domain associated protein alpha), a beta1 integrin associated protein. A particular mutation in CCM1 (the Q455X mutation), accounts for a cluster of cases in the Southwestern United States. This cluster, particularly in northern New Mexico, is an example of the founder effect; it has been traced back to early Spanish settlers. The gene for CCM2 encodes a protein named malcavernin that contains a phosphotyrosine (PTB) binding domain. The exact biological function of CCM2 is not clear. Recently, it has been shown that CCM1 and CCM2 proteins as well as ICAP1alpha form a macromolecular complex in the cell. In addition, it appears that CCM2 protein may function as a scaffolding protein for MAP kinases that are essential in p38 activation responding to osmotic stress including MEKK3 and MKK3. It also binds to Rac and actin. Therefore, CCM2 protein is also called OSM (osmosensing scaffold for MEKK3). The CCM3 gene is the most recently identified CCM gene . CCM3 is known as PDCD10 (programmed cell death 10), which was initially identified as a gene that is up-regulated during the induction of apoptosis (cell death) in TF-1, a human myeloid cell line. The precise role of the PDCD10 protein in the CCM pathway is not clear. It is recently shown that PDCD10 forms a complex with CCM1 protein (KRIT1) and CCM2 protein (OSM). PDCD10 interacts directly with OSM independent of KRIT1-OSM interaction. Research is ongoing to determine the function and properties of all three CCM gene products as well as the reaction pathways in which they are involved. Evidence suggests that a fourth gene, CCM4, may also cause CCM. Mutations in these genes account for 70 to 80 percent of all cases of cerebral<unk>  malformations. The remaining 20 to 30 percent of cases may be due to other, still unidentified, genes. Recently it has been shown that the deletion of CDC42 in endothelial cells elicits cerebral vascular malformations, suggesting that it may be a fourth gene involved in CCM pathology.
Central nervous system cavernous hemangioma
Brain metastasis
Optic nerve glioma
Vein of Galen aneurysmal malformations
Central nervous system cyst
Leptomeningeal cancer
Primary central nervous system lymphoma
Optic nerve sheath meningioma