Von Hippel-Lindau disease (VHL) is a rare, genetic multi-system disorder of congenital capillary angiomatous hematomas. These benign nests of blood vessels called hemangioblastomas may develop in the brain, the retina and other areas of the nervous system, such as the cerebellum and spinal cord. Eugen von Hippel described the angiomas in the eye in 1904. Arvid Lindau described the angiomas of the cerebellum and spine in 1927. Other types of tumors develop in the adrenal glands, the kidneys or the pancreas. Symptoms of VHL vary among patients and depend on the size and location of the tumors.
Symptoms of Von Hippel-Lindau Disease
Von Hippel-Lindau disease usually presents in the second to third decade of life. Angiomas are the most common presenting signs and symptoms of VHL. Angiomatosis, hemangioblastomas, pheochromocytoma, renal cell carcinoma, pancreatic cysts and café au lait spots (pigmented birthmarks) are all associated with VHL. Angiomatosis occurs in 37.2% of patients presenting with VHL and usually occurs in the retina, however other organs can be affected. Retinal capillary hemangiomas (von Hippel disease) are seen in 50% of patients. Only about 20% of people with VHL get pheochromocytomas.
Central nervous system (CNS) hemangioblastomas occur in 60-80% of patients (infratentorial in 60 %, intraspinal in 30-40% and supratentorial in 1% of cases). Multiple tumors are frequent (hemangioblastomatosis). These may cause life-threatening complications in spite of their benign nature, slow-growing course and remain a major cause of morbidity and mortality. Frequent symptoms include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, blindness and high blood pressure. Cysts (fluid-filled sacs) and/or tumors (benign or cancerous) may develop around the hemangioblastomas and cause the symptoms. Individuals with VHL are also at a higher risk than normal for certain types of cancer, especially kidney cancer. VHL disease is the first cause of hereditary kidney cancer.
Causes of Von Hippel-Lindau Disease
VHL results from a mutation in the tumor-suppressor gene on chromosome 3p25.3. If one parent has a dominant gene, each child has a 50-50 chance of inheriting that gene (autosomal dominant).
Exams and Tests for Von Hippel-Lindau Disease
- Vanillylmandelic acid levels in urine
- Genetic study analysis
Neuroimaging advances have allowed early interventions and effective outcomes.
- CT scan of brain with contrast
- MRI of brain (posterior fossa emphasis)
- Abdominal CT scan (to look for pheochromocytoma)
- Ophthalmic ultrasound
- Ocular color Doppler sonography
- Optical coherence tomography (OCT)
The ophthalmologist has a critical role to play in the management of von Hippel-Lindau disease.
Treatment of Von Hippel-Lindau Disease
Von Hippel-Lindau disease is usually a progressive disease. Surgical treatment may consist of argon laser photocoagulation, cryotherapy, fluid drainage, scleral buckling, penetrating diathermy, vitreous surgery, or endodiathermy. VHL varies according to the location and size of the tumor and its associated cyst. In general, the objective of treatment is to treat the growths when they are causing symptoms, but while they are still small so that they do not cause permanent problems by putting pressure on the brain or spine, blocking the flow of cerebrospinal fluid in the nervous system, or impairing vision. Certain tumors can be treated with Stereotactic Radiation and Radio Frequency Ablation.
Prognosis of Von Hippel-Lindau Disease
Untreated, VHL may result in blindness and/or permanent brain damage. With early detection and treatment, the prognosis is significantly improved. Death is usually caused by complications of brain tumors or kidney cancer. Mean age at death is about 50 years, and renal cell carcinomas and central nervous system hemangioblastomas are the major causes of death.
For further information about Von Hippel-Lindau, please refer to the following organizations or click on the following links:
National Organization for Rare Disorders (NORD)
P.O. Box 1968
(55 Kenosia Avenue)
Danbury, CT 06813-1968
Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
International RadioSurgery Association
3002 N. Second Street
Harrisburg, PA 17110