This is a closely related congenital neurocutaneous disorder in which a specific skin lesion (epidermal nevus or linear sebaceous nevus) is associated with a variety of hemicranial and neurologic abnormalities. The skull and brain abnormalities are ipsilateral to the nevus. One-sided thickening of the bones of the skull is characteristic. Developmental delay, seizures, and hemiparesis are the usual neurologic manifestations and have their basis in a wide variety of cerebral lesions—unilateral cerebral atrophy, porencephalic cyst, leptomeningeal hemangioma, arteriovenous malformation, and atresia of cerebral arteries and veins. The somatic and neurologic abnormalities of this syndrome have been comprehensively reviewed by
Solomon and Esterley and by Baker and associates.
This vascular anomaly is transmitted as an autosomal dominant trait. To date, two mutant genes have been identified as causes of this disease: endoglin and novel kinase. The small arteriovenous malformations affect the skin, mucous membranes, gastrointestinal and genitourinary tracts, lungs, and occasionally the nervous system. The basic lesion is probably a defect in the vessel wall, and the main complication, bleeding, is thought to be a result of the mechanical fragility of the vessel. Located sparsely in the skin of any part of the body, these vascular lesions first appear during childhood, enlarge during adolescence, and may assume spidery forms, resembling the cutaneous telangiectases of cirrhosis in late adult life. The lesions range from the size of a pinhead to 3 mm or more, are bright red or violaceous, and blanch under pressure.
The significance of the lesions lies in their hemorrhagic tendency. During adult years they may give rise to severe and repeated epistaxis or gastric, intestinal, or urinary tract bleeding and result in an iron-deficiency anemia. Pulmonary fistulas constitute another important feature of the generalized vascular dysplasia; patients with such lesions are particularly subject to brain abscesses and less so to bland embolic strokes.
The angiomas of this disease may infrequently form in either the spinal cord or brain, where they can produce acute hemorrhage, or as in one of our patients, there may be an intermittently progressive focal thalamic syndrome resulting from enlargement of the vascular lesions or possibly from a succession of small hemorrhages. Repeated unexplained gastrointestinal, genitourinary, intracranial, or intraspinal hemorrhages warrant a search for small cutaneous lesions, which are easily overlooked. Satellite lesions tend to form after obliteration of an angioma.
There are five genetic types with hundreds of mutations known. A mutation in the gene coding for endoglin (ENG) accounts for most cases with a smaller proportion due to a mutation in the gene for activin (ACVRL1), both proteins involved in angiogenesis but the actual mechanism of formation of the main feature, vascular malformations, is not completely understood.
This is a genetic disease of multiple neoplasms, specifically by the presence of a hemangioblastoma, sometimes multiple (these are discussed with other cerebral tumors in Chap. 30). The tumor is situated in the cerebellum in most cases, but may also arise in the brainstem or spinal cord. In addition to the characteristic cerebellar tumor with its nodule within a cyst, half of these patients have retinal hemangioblastomas and somewhat fewer develop renal cell cancer; an even smaller number have a pheochromocytoma, pancreatic tumors or cysts, or cystadenomas. Polycythemia vera is an interesting feature in a few cases. We have encountered rare cases that presented as subarachnoid hemorrhage.