Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations.

Abstract

Pathogenesis of cerebral venous malformation (CVM) is unknown. Because of coexistence of CVM and cerebral cavernous malformations (CCM), some studies have suggested that these 2 entities share a common origin and pathogenetic mechanism. We have identified and ascertained over 200 families with CCM. Among these, 1 unique family was found to have members affected by both disorders. We have performed mutational analysis in all 3 CCM genes, KRIT1, Malcavernin, and PDCD10, to identify the causative gene in the family. Mutational analysis revealed a frameshift mutation affecting exon 19 of the CCM1 gene (KRIT1) in members with CCM, whereas no such mutation was observed in the member with CVM. These findings support the hypothesis that CVM and CCM are 2 distinct entities with different pathogenetic mechanisms. This data further supports the hypothesis that CVM has a distinct biology and clinical behavior when compared to CCM. CVM is a benign developmental anomaly and should be managed separately from CCM.