Scattered reports of angiomatous lesions of the retina causing blindness and sometimes associated with identical lesions in the cerebellum began in 1864 and were written by ophthalmologists. In 1894, Collins, an English ophthalmologist, described angiomas of the eye in two siblings (5). Von Hippel, a German ophthalmologist, first recognized the familial nature of retinal hemangioblastomas (6). However, Arvid Lindau, a Swedish ophthalmologist from Lund is credited with the critical observations that cerebellar and retinal hemangioblastomas are part of a larger "angiomatous lesion of the central nervous system" and that the condition was heritable (7). Familial cerebellar hemangioblastomas are still sometimes referred to as "Lindau's" tumors. Although he observed the classic visceral manifestations of renal and pancreatic involvement, Lindau chose to downplay these findings since he thought they were asymptomatic. Subsequent scattered clinical reports of small families confirmed the association of CNS hemangioblastomas (Hb) and renal and pancreatic cysts, pheochromocytomas, renal cell carcinomas, and epididymal cystadenomas. These results were summarized in a landmark paper in 1964 by Melmon and Rosen, who described a large VHL family and codified the term "von Hippel-Lindau" (8). Identification of affected members was greatly aided by the advent of CT and ultrasound in the 1970s and early 1980s and resulted in the description of several large families from around the world (9-13). Later, MRI became a key screening method for the cerebellum and spine. In the 1980s several families with non-VHL hereditable renal cancer and chromosomal translocations involving the short arm of the third chromosome were found (14-16). This led to genetic linkage studies focussed on chromosome 3 which ultimately localized the gene to the short arm of this chromosome (3p25-26) in the late 80s and early 90s. In 1993 the " VHL gene" was identified by researchers at the National Cancer Institute (3).
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