Von Hippel Lindau Syndrome (VHL) is familial predisposition to develop multiple clear cell neoplasms in various organs including the retina, central nervous system (CNS) hemangioblastomas (most frequently cerebellar and spinal), renal cell carcinomas, pheochromocytomas, pancreatic endocrine tumors, and cysts.
Familial Cerebello-Retinal Angiomatosis.
There are four different phenotypes depending on the type of mutation of the VHL gene:
Type 1: Retinal angiomas hemangioblastomas of the CNS, renal cell carcinoma, pancreatic cysts, tumors neuroendocrine, low risk of pheochromocytoma.
Type 2A: High risk of pheochromocytoma, retinal angiomas, hemangioblastomas of the SNC, low risk of renal cell carcinoma.
Type 2B: High risk of pheochromocytoma, retinal angiomas, CNS hemangioblastomas, high risk of renal cell carcinoma.
Type 2C: High risk of pheochromocytoma.
Annual incidence 1:36,000 and prevalence 1:53,000.
Autosomal dominant. Mutations of the VHL gene (tumor suppressor gene) on 3p25.3. The gene is a putative tumor suppressor gene and also implicated in the development of sporadic tumors including clear cell renal carcinoma and CNS hemangioblastoma.
Interfamilial differences in predisposition to pheochromocytoma in VHL reflect allelic heterogeneity such that there is a strong association between missense mutations and risk of pheochromocytoma.
The presence of visceral cysts of the kidney, pancreas, and epididymis occurs not only as features of VHL but also in the general population. However, the association of those cysts with retinal, CNS hemangioblastoma may represent a more significant association for the disease. The use of markers as presymptomatic diagnosis of VHL in patients with epididymal cysts has been demonstrated to be not suitable as a diagnostic criterion. Similarly, the genetic studies suggested that VHL with or without pheochromocytomas is caused by defects within the same gene may be misleading. It has been suggested that the likelihood of VHL being present in an individual showing a single ocular angioma is conditional upon the age of presentation, results of deoxyribonucleic acid (DNA) analysis, family history of VHL, and results of systemic screening.
The cardinal features of von Hippel Lindau Syndrome are angiomata of the retina and hemangioblastoma of the cerebellum and/or spinal cord. Hemangioma of the spinal cord has also been reported. Pheochromocytoma occurs in some patients and will help in the classification. The combination of hypertension with angioma may lead to subarachnoid hemorrhage and the consequences associated with this clinical presentation. Hypernephroma-like renal tumors occur in some patients. Polycythemia may be due to either the hemangioblastoma of the cerebellum or the hypernephroma. Hemangiomas of the adrenals, lungs, and liver, and multiple cysts of the pancreas and kidneys have been observed in some instances.