Read more about this disease, some with Classification – Types – Signs and symptoms – Genetics – Pathophysiology – Diagnosis – Screening – Prevention – Treatment and management – Cures and much more, some including pictures and video when available.
Von Hippel-Lindau disease (VHL) is a rare, autosomal dominant genetic condition in which haemangioblastomas are found in the cerebellum, spinal cord and retina. These are associated with several pathologies including renal angioma, renal cell carcinoma and phaeochromocytoma. VHLD results from a mutation in the tumour-supressor gene on chromosome 3p25.3.[1]
Other names are: angiomatosis retinae, angiophakomatosis retinae et cerebelli, familial cerebello-retinal angiomatosis, cerebelloretinal hemangioblastomatosis, Hippel Disease, Hippel-Lindau syndrome, HLS, Lindau disease or retinocerebellar angiomatosis.
VHL may be diagnosed when one of its associated diseases starts to cause discomfort in the person suffering from the disease. Angiomatosis, haemangioblastomas, pheochromocytoma, renal cell carcinoma, pancreatic cysts and café au lait spots are all associated with VHL.[2] Angiomatosis occurs in 37.2% of patients presenting with VHLD and usually occurs in the retina, however other organs can be affected. As a result, loss of vision is very common.[1]
The disease is caused by mutations of the Von Hippel-Lindau tumor suppressor (VHL) gene on the short arm of third chromosome.
As long as one copy of the VHL gene is producing functional VHL protein in each cell, tumors do not form. If a mutation occurs in the second copy of the VHL gene during a person’s lifetime, the cell will have no working copies of the gene and will produce no functional VHL protein. A lack of this protein allows tumors characteristic of von Hippel-Lindau syndrome to develop.
Since both alleles need to be mutated in order for the disorder to develop, it would be likely to conclude that the mutation is recessive. However, studying the patterns of heredity, we see that VHL is, paradoxally, an autosomal dominant disorder. This is because people who have already inherited one mutated copy of the gene have an extremely high probability of developing the second mutation. An inherited mutation of the VHL gene is responsible for about 80 percent of cases. In about 20 percent of cases, however, the altered gene is the result of a new mutation that occurred during the formation of reproductive cells (eggs or sperm) or early in fetal development. This is quite rare because the probability of a mutation occuring in a cell where both alleles are previously normal is quite small. Also, the first mutation needs to be followed by a second one in order for the syndrome to develop.
There is a wide variation in the age of onset of the disease, the organ system affected and the severity of effect. This suggests that the second mutation can occur in different types of cells and at various times of a person’s life.
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