Clinical Characteristics
Ocular Features
Cavernous capillary hemangiomas usually occur singly in the fundus, often at the disc. Fewer than 5% of individuals with CCM have retinal lesions. As opposed to the systemic hemangiomas, those in the eye tend to be stable. However, they may result in vitreous hemorrhages because they lack the usual structural support of normal vessels. Fluorescein angiography often reveals blood-fluid levels in the saccules that comprise the grape-like cluster of the tumor.
Systemic Features
Cavernous angiomas may involve any part of the CNS, brain stem, and spinal cord. These are benign aberrant growths of capillary endothelium which develop shortly after birth and cause a variety of signs and symptoms including seizures, intracranial hemorrhage, and focal neurologic deficits. New lesions can appear throughout life. The blood –containing clusters are lined with endothelium only and the walls lack muscle or fibrous tissue. Up to 25% are diagnosed in children. They may be angiographically silent but MRI is diagnostically useful. Cutaneous hemangiomas are uncommon but helpful diagnostically when present. The overlying skin may be hyperkeratotic.
Many patients (25-50%) remain asymptomatic throughout life.
Genetics
Inheritance
This is an autosomal dominant disorder caused by mutations in three genes. CCM1 (116860) results from mutations in the KRIT1 gene located at 7q11.2-q21, the disease called CCM2 (603284) is caused by mutations in the CCM2/malcavernin gene (7p13), and CCM3 (603285) by mutations in the PDCD10 gene at 3q26.1. The majority of familial cases have mutations in one of these genes.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission