A Review of Von Hippel-Lindau Syndrome

Abstract

Von Hippel-Lindau syndrome (VHL) is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

A Painful Finger: An Unusual Presentation of Von Hippel-Lindau-Associated Advanced Renal Cell Carcinoma

“…VHL gene codes for the VHL protein, which is involved in ubiquitin-dependent proteolysis pathways, hypoxia-inducible factors degradation and subsequent expression of angiogenic and growth factors such as vascular endothelial growth factor [8]. This syndrome predisposes affected individuals to the development of benign and malignant tumours including cysts of the central nervous system, kidney and pancreas, haemangioblastomas, renal cell carcinoma, phaeochromocytoma, neuroendocrine tumours and cystadenomas of the broad ligament and epididymis [9]. The incidence is estimated to be at 1 in 36,000 live births, with a penetrance of over 90% by the age of 65.…”

Updates on the Role of Molecular Alterations and NOTCH Signaling in the Development of Neuroendocrine Neoplasms

“…The Von Hippel-Lindau (VHL) syndrome is associated with pheochromocytomas, paragangliomas and pancreatic neoplasia and it is caused by the loss of VHL tumour supressor gene, regulating the HIF and VEGF pathways [31][32][33]. The VHL protein shuttles between nucleus and cytoplasm binding to elongen C, elongen B, Cul2, and Rbx1 and degrading the alpha subunits of hypoxia-inducible factor (HIF) in an oxygen-dependent manner [32 ,34, 35].…”

Ultraweitwinkel-Fundusfotografie und -angiografie in der Differenzialdiagnose und zur Therapieplanung bei peripheren vaskulären Netzhauterkrankungen

“…Sporadische und hereditäre Angiome können klinisch nicht differenziert werden. VHL ist autosomaldominant vererbt; 80 % ererbt von einem betroffenen Elternteil, 20 % De-novo-Mutationen [29].…”