question: What is known as Von Hippel–Lindau disease or syndrome?
answer: von Hippel-Lindau (VHL) disease is a rare, autosomal dominantly inherited multisystem disorder characterized by development of a variety of benign and malignant tumors, which are usually accompanied with cysts. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The most common causes of death in VHL disease patients are renal cell carcinoma and neurologic complications from cerebellar hemangioblastomas. von Hippel-Lindau (VHL) syndrome is associated with mutations of the VHL tumor suppressor gene (3p25-26). Its estimated incidence ranges from 1 in 36,000 to 1 in 53,000 with a penetrance of up to 95% by age 60. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation. Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes.In addition, many HIFalpha-independent functions of pVHL have recently been identified. These include microtubule-based processes, extracellular matrix assembly and suppression of kidney cyst formation.