Familial cerebral cavernous malformation

Familial cerebral cavernous malformation (CCM), also known as familial cavernous angioma or familial cavernomatosis, is a genetic vascular disorder characterized by the formation of clusters of abnormally dilated, thin-walled blood vessels (cavernomas or cavernous hemangiomas) primarily within the brain and spinal cord. These lesions lack the normal structural support of healthy blood vessels and are prone to leaking blood into surrounding neural tissue. The condition predominantly affects the central nervous system, though cavernous malformations can occasionally occur in the skin, retina, or liver. Clinical manifestations are highly variable, even within the same family. Many individuals remain asymptomatic throughout life, while others develop seizures (the most common presenting symptom), recurrent headaches, focal neurological deficits (such as weakness, numbness, vision changes, or balance problems), and hemorrhagic stroke due to bleeding from the malformations. Symptoms typically begin in the second to fifth decades of life but can present at any age. The number and size of lesions tend to increase over time in familial cases, which distinguishes them from sporadic forms where usually only a single lesion is present. Familial CCM is caused by pathogenic variants in one of three genes: CCM1 (KRIT1, on chromosome 7q), CCM2 (MGC4607/malcavernin, on chromosome 7p), and CCM3 (PDCD10, on chromosome 3q). Mutations in CCM1 account for the majority of familial cases, particularly in individuals of Hispanic-American descent who share a common founder mutation. Diagnosis is established through brain MRI, which reveals characteristic mulberry-like lesions, and can be confirmed by genetic testing. Treatment is primarily symptomatic, including antiepileptic medications for seizure control. Surgical resection of accessible, symptomatic lesions may be considered when the benefits outweigh the risks. There is currently no approved pharmacological therapy to prevent lesion formation or growth, though clinical trials investigating potential medical treatments are ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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