Walsh & Hoyt: Clinical Features

The primary manifestations of VHLD are retinal angiomas, hemangioblastomas, and renal cell carcinoma. In contrast to the early manifestations of neurofibromatosis and tuberous sclerosis, recognition in VHLD is commonly in the third decade . In one study of 38 kindreds with VHLD, penetrance reached 0.96 in the sixth decade and 0.99 in the seventh decade. Besides the slow rate of expression, the manifestations of the genetic defect in VHLD are varied. In a study of 152 affected patients, the first sign of the disease was retinal angiomas in 43%, hemangioblastomas in 39%, and renal cell carcinoma in 10%. Mean age of onset was the earliest for retinal angiomas at 25.4 years; hemangioblastomas were slightly later at 29.0 years, and renal cell carcinomas were the latest at 44.0 years; the probability of developing a retinal angioma, renal cell carcinoma, or hemangioblastoma by 60 years of age was 0.7, 0.69, and 0.84, respectively. Beyond the age of 60 years, expression in a heterozygote becomes remote. The pancreas, epididymis, and adrenal medulla are affected at a lower rate. In one analysis of 92 affected subjects, retinal angiomas and hemangioblastomas affected most families, but renal lesions or pancreatic cysts and pheochromatocytoma occurred in some families without ocular and neurologic tumors.