Von Hippel-Lindau syndrome (VHL) is an autosomal dominant multisystem disorder characterized by hemangioblastomas of the central nervous system (CNS), clear cell renal cell carcinoma (kidney cancer), pheochromocytomas (a type of non-cancerous tumor), islet cell tumors of the pancreas, endolymphatic sac tumors, cysts (renal, pancreatic, and epididymal), and a predisposition to bilateral and multicentric retinal angiomas. The disease has a prevalence rate of 1 in 36000 birth.
Retinal angiomas may be the initial manifestation of VHL syndrome and can cause vision loss, while CNS hemangioblastoma (Lindau tumor) is the most commonly recognized finding of VHL syndrome that occurs in 40% of patients. Renal cell carcinoma occurs also in about 40% of the patients and it is the main cause of mortality. Endolymphatic sac tumors occur in 10% of the cases and can cause hearing loss. The incidence of VHL syndrome is thought to be about one in 36,000 live births. Both genders are equally affected, and about 20% of the cases are familial.
The classification of VHL syndrome phenotypes depends on the risk of developing pheochromocytoma or renal cell carcinoma. VHL type 1 has a low risk for pheochromocytoma, whereas VHL type 2 has a high risk for pheochromocytoma. VHL type 2 is further subdivided into: type 2A (with low risk of renal cell carcinoma), type 2B (with high risk of renal carcinoma), and type 2C (has risk for pheochromocytoma only). A new VHL phenotype is identified to have a low risk for both renal cell carcinoma and pheochromocytoma.
Von Hippel-Lindau syndrome is associated with mutations in Von Hippel-Lindau tumor suppressor (VHL) gene. Cyclin D1 gene (CCND1) variants are also known to contribute to the phenotype by acting as a modifier.
