Von Hippel–Lindau disease (VHL) is a rare hereditary neurocutaneous disorder characterized by benign and malignant tumors in multiple organs.
VHL most commonly causes cerebellar hemangioblastomas and retinal angiomas. Tumors, including pheochromocytomas and cysts (renal, hepatic, pancreatic, or genital tract), can occur in other organs. About 10% of people with VHL develop an endolymphatic tumor in the inner ear, threatening hearing. Risk of developing renal cell carcinoma increases with age and by age 60 may be as high as 70%. Manifestations typically appear between ages 10 and 30 but can appear earlier.
The disorder occurs in 1 of 36,000 people and is inherited as an autosomal dominant trait with variable penetrance. The VHL gene is located on the short arm of chromosome 3 (3p25.3). In 20% of affected people, the abnormal gene appears to be a new mutation.
Symptoms and Signs
Symptoms depend on the size and location of the tumors. Symptoms may include headaches, dizziness, weakness, impaired vision, and high BP.
Retinal angiomas, detected by direct ophthalmoscopy, appear as a dilated artery leading from the disk to a peripheral tumor with an engorged vein. These angiomas are usually asymptomatic, but if they are centrally located and enlarge, they can result in substantial loss of vision. These tumors increase risk of retinal detachment, macular edema, and glaucoma.
Untreated, VHL can result in blindness, brain damage, or death. Death usually results from complications of cerebellar hemangioblastomas or renal cell carcinoma.
The disorder is diagnosed when typical tumors are detected and one of the following criteria is met:
If one cerebellar hemangioblastoma, retinal angioma, or pheochromocytoma is detected, clinicians should look for other tumors.
Genetic testing is done to check for an abnormal VHL gene in at-risk family members. If an abnormal gene is detected, family members are monitored for tumors for the rest of their life.
Treatment often involves surgical removal of the tumor before it becomes harmful. Some tumors can be treated with focused high-dose radiation. Typically, retinal angiomas are treated with laser coagulation or cryotherapy to preserve vision.
Patients should be monitored regularly for progression of the disorder. Appropriate monitoring and treatment can improve prognosis.
Last full review/revision September 2013 by Margaret C. McBride, MD
Content last modified October 2013