Cerebral cavernous malformation

Cerebral cavernous malformations (CCMs) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls that are prone to leak. They also lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, when the capillaries fill with blood, they stretch out and may not return to their normal size when the blood vessels empty. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the central nervous system (the brain and spinal cord).

Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related medical problems. Other people with cerebral cavernous malformations may experience serious symptoms such as headaches, seizures, paralysis, hearing or vision deficiencies, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time, but they do not become cancerous.

Cerebral cavernous malformations affect about 0.5 percent of the population worldwide.

Mutations in the CCM2, KRIT1, and PDCD10 genes cause cerebral cavernous malformation.

The precise functions of these genes are not fully understood, but they most likely play a role in blood vessel formation (angiogenesis) during embryonic development. They may also play a role in maintaining existing blood vessels. Researchers have not determined how mutations in these genes can lead to the abnormal capillaries characteristic of cerebral cavernous malformations.

Mutations in these three genes account for 70 percent to 80 percent of all cases of familial cerebral cavernous malformations. The remaining 20 percent to 30 percent of cases may be due to unidentified genes or to other unknown causes.

Read more about the CCM2, KRIT1, and PDCD10 genes.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent.

Most cases of cerebral cavernous malformation result from a new mutation in the KRIT1, CCM2, or PDCD10 gene. These cases are known as sporadic, and they occur in people with no history of the disorder in their family.