Definition of Von Hippel-Lindau syndrome

Von Hippel-Lindau syndrome: A genetic disease characterized by:

• hemangioblastomas (benign blood vessel tumors) in the brain, spinal cord, and retina;
• kidney cysts and kidney cancer (renal cell carcinoma);
• pheochromocytoma (a benign tumor of adrenal-like tissue); and
• endolymphatic sac tumors (benign tumors of the labyrinth in the inner ear).

The brain hemangioblastomas in Von Hippel-Lindau (VHL) syndrome are usually in the cerebellum and can cause headache, vomiting, and gait disturbances or ataxia (wobbliness). The hemangioblastomas in the retina can cause vision loss and may be the initial sign of the syndrome. Renal cell carcinoma occurs in 40% of cases and is the leading cause of death. Pheochromocytomas can cause no symptoms or constant or episodic high blood pressure. The endolymphatic sac tumors can diminish hearing, a key symptom.

VHL is inherited in an autosomal dominant manner and is caused by a change affecting the VHL gene, a tumor-suppressor gene, on chromosome 3 (region 3p26-p25). This change is a point mutation in the VHL gene in three-quarters of cases and a partial or complete deletion of the gene in the remaining cases.

Molecular genetic testing for the VHL gene confirms the diagnosis. The change in VHL is inherited in about 80 percent of cases while in the other 20 percent it is a new occurrence. In all families, there is a 50 percent risk for each child of a person with VHL of inheriting the VHL disease-causing mutation. Prenatal testing is available. Early recognition of the VHL syndrome is of importance because it permits timely intervention and may be lifesaving.

The syndrome is named for the German ophthalmologist Eugen von Hippel who described the characteristic eye blood-vessel tumors in 1904 and the Swedish pathologist Arvid Lindau who recognized the association between the eye tumors and the blood-vessel tumors of the cerebellum and other parts of the central nervous system in 1926-7.

Common Misspellings: von hippel-lindau syndrone