Background: Cerebral cavernous malformations exist in sporadic and familial forms. They have considerable genetic and clinical heterogeneity. Better understanding of these disorders may improve management.
Material and methods: This review is based on personal experience and recent literature.
Results: Cerebral cavernous malformations are venous malformations that can be detected with gradient echo MRI of the brain. Approximately 0.5% of the general population have the sporadic form with a single or a few cerebral cavernous malformations which mostly are asymptomatic. Those with the familial form usually have several cavernous malformations caused by an autosomal dominant condition. So far, 3 loci have been identified: CCM1 on chromosome 7q, CCM2 on chromosome 7p, and CCM3 on chromosome 3q, occurring in, respectively, approximately 40%, 20% and 40% of the families. CCM1 is caused by a mutation in the KRIT1 gene and CCM2 is caused by a mutation in the MGC4607 gene, while the gene for CCM3 is not yet identified. Mean age at onset is 20-40, but onset can occur at all ages. The most frequent symptoms are seizures, cerebral haemorrhage, chronic headache and focal neurological deficits. Many carriers are, however, asymptomatic.
Interpretation: Sporadic cerebral cavernous malformation is often asymptomatic, while the familial form shows phenotypic and genetic heterogeneity. The symptoms are depending on the location of the malformations as well as whether haemorrhage does occur.