A cavernoma is an abnormal cluster of small, thin-walled blood vessels, most often found within the brain or spinal cord. This malformation, sometimes called a cerebral cavernous malformation (CCM), is distinct from a tumor because it does not involve rapidly dividing cells, though it can grow and cause symptoms. Cavernomas are often described as resembling a raspberry or a popcorn-like mass because they consist of dilated, blood-filled channels. The thin walls of these abnormal vessels lack the structural support of normal capillaries, making them prone to leaking blood into the surrounding nervous tissue.
Distinguishing Inherited from Sporadic Origins
Cavernoma development falls into two categories: inherited (familial) and acquired (sporadic). The majority of cases, estimated at about 80%, are sporadic, occurring randomly in individuals with no family history. These sporadic lesions typically present as a single malformation in the central nervous system. Familial cases account for the remaining 15% to 20% of diagnoses and are characterized by a genetic link. Individuals with the inherited form generally develop multiple lesions throughout their brain and spinal cord over time.
The Role of Genetics in Familial Cases
Familial cavernomas result from a mutation in one of three primary genes (CCM1, CCM2, or CCM3), passed down through autosomal dominant inheritance, meaning only one altered copy is needed for susceptibility. These genes produce proteins that regulate the health and structure of blood vessel walls by forming a complex at the junctions between endothelial cells. When a gene is mutated, the resulting dysfunctional protein breaks down the integrity of the vessel lining. This weakening allows the formation of fragile, leaky cavernoma lesions. CCM3 mutations are often linked to a more aggressive form and a higher number of lesions.
Environmental and External Triggers
Sporadic cavernomas are not inherited but result from a somatic mutation acquired after conception, often involving the same CCM genes as the familial form. Sporadic lesion development follows a “two-hit” mechanism, where the initial genetic change is followed by a second trigger that causes the lesion to form. The most well-established external factor linked to cavernoma acquisition is cranial radiation exposure. Cavernomas can begin to form several years after a person has undergone radiation therapy to the head, often for a different brain tumor. These radiation-induced cases frequently result in multiple lesions, a feature usually associated with the inherited type.