Von Hippel–Lindau disease (VHL) is a rare hereditary neurocutaneous disorder characterized by tumors in multiple organs.

VHL most commonly causes cerebellar hemangioblastomas and retinal angiomas. Tumors, including pheochromocytomas and cysts (renal, hepatic, or pancreatic), can occur in other organs; 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 is inherited as an autosomal dominant trait with variable penetrance. The VHL gene is located on the short arm of chromosome 3.

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.

Diagnosis

The disorder is diagnosed when typical tumors are detected and one of the following criteria is met:

• More than one tumor in the brain or eye
• Single tumor in the brain or eye and one elsewhere in the body
• Family history of VHL and presence of a tumor

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

• Surgery or sometimes radiation therapy
• For retinal angiomas, laser coagulation or cryotherapy
• Regular monitoring

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 March 2009 by Margaret C. McBride, MD