Von Hippel-Lindau syndrome is a genetic condition that causes tumors and fluid-filled sacs (cysts) to grow in various regions of the body. Tumors can be noncancerous or cancerous, and they most commonly emerge during adolescence; however, the signs and symptoms of von Hippel-Lindau disease can appear at any age.
Von Hippel-Lindau syndrome is characterized by tumors termed hemangioblastomas. These growths are blood vessels that have just developed.They can create significant or life-threatening issues, despite the fact that they are usually noncancerous. Headaches, vomiting, weakness, and a lack of muscular coordination are all symptoms of hemangioblastomas that grow in the brain and spinal cord (ataxia).
The light-sensitive tissue that borders the back of the eye can potentially develop hemangioblastomas (the retina). These tumors, also known as retinal angiomas, can result in visual loss.
Cysts in the kidneys, pancreas, and genital tract are prevalent in people with von Hippel-Lindau syndrome.They're also more likely to develop clear cell renal cell carcinoma, a kind of kidney cancer, and pancreatic neuroendocrine tumors, a type of pancreatic cancer.
Pheochromocytoma, a form of tumor that most typically affects the adrenal glands, is linked to Von Hippel-Lindau disease (small hormone-producing glands located on top of each kidney).
Pheochromocytomas are noncancerous tumors.They may have no symptoms, but they have been linked to headaches, panic episodes, excessive perspiration, and dangerously high blood pressure that may not react to medicine in certain circumstances. Pheochromocytomas are especially harmful at times of stress or trauma, such as while undergoing surgery or being involved in an accident, or when pregnant.
Endolymphatic sac tumors, which are noncancerous tumors in the inner ear, affect around 10% of persons with von Hippel-Lindau disease. These tumors can cause hearing loss in one or both ears, as well as tinnitus (ringing in the ears) and balance issues. These tumors can induce abrupt severe deafness if not treated. In persons with von Hippel-Lindau syndrome, noncancerous tumors can form in the liver and lungs. There are no indications or symptoms associated with these malignancies.
Causes
Von Hippel-Lindau syndrome results from VHL gene mutations. The VHL gene is a tumor suppressor gene, which means it prevents cells from dividing and developing too quickly or uncontrollably. This gene's mutations either prohibit the VHL protein from being produced or cause it to be produced in an aberrant form. The survival and division of cells cannot be adequately controlled if the VHL protein is changed or absent. As a result, cells expand and divide uncontrolled, resulting in the tumors and cysts associated with von Hippel-Lindau syndrome.
Inheritance
VHL gene mutations are inherited in an autosomal dominant way, meaning that one copy of the changed gene in each cell is enough to raise the risk of tumors and cysts. Von Hippel-Lindau syndrome is caused by an abnormal copy of the gene inherited from an afflicted parent. The changed gene is the outcome of a novel mutation that happened during the creation of reproductive cells (eggs or sperm) or very early in development in roughly 20% of instances.
Unlike other autosomal dominant disorders, where one mutated copy of a gene in each cell is enough to induce the ailment, von Hippel-Lindau syndrome requires two copies of the VHL gene to promote tumor and cyst development. During a person's lifespan, a mutation in the second copy of the VHL gene arises in select cells within organs such as the brain, retina, and kidneys. Tumors and cysts can form when cells with two mutated copies of this gene fail to produce functional VHL protein. Almost everyone who inherits one VHL mutation will get a mutation in the second copy of the gene in some cells, resulting in von Hippel-Lindau syndrome symptoms.
Other Names for This Condition
- Angiomatosis retinae
- Cerebelloretinal angiomatosis, familial
- Hippel-Lindau disease
- VHL syndrome
- Von Hippel-Lindau disease
Von Hippel-Lindau (VHL) syndrome is characterized by hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma, pancreatic cysts, and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts. Cerebellar hemangioblastomas may be associated with headache, vomiting, gait disturbances, or ataxia. Spinal hemangioblastomas and related syrinx usually present with pain. Sensory and motor loss may develop with cord compression. Retinal hemangioblastomas may be the initial manifestation of VHL syndrome and can cause vision loss. Renal cell carcinoma occurs in about 70% of individuals with VHL and is the leading cause of mortality.
Although pheochromocytomas are often asymptomatic, they can induce chronic or episodic hypertension. Pancreatic lesions are generally asymptomatic and only cause endocrine or exocrine insufficiency in a small percentage of cases. Hearing loss of various intensity can be a presenting sign of endolymphatic sac tumors. Epididymis cystadenomas are rather frequent. They seldom create difficulties unless they are bilateral, in which case infertility is a possibility.
Diagnosis
Von Hippel-Lindau disease can be diagnosed using clinical criteria (signs and symptoms) or molecular genetic testing that identifies a change (mutation) in the VHL gene.
The following tests may be used to make a clinical diagnosis:
- MRI of the brain and spinal cord
- Fundoscopy
- Ultrasound examination or MRI of the abdomen
- Blood and urinary catecholamine metabolites.
Treatment
Treatment for Von Hippel-Lindau disease (VHL) is determined by the location and size of the tumors. The idea is to address growths that are causing symptoms but are still tiny enough not to cause irreparable harm. Tumors are frequently surgically removed as part of treatment. In some circumstances, radiation treatment may be employed. All patients who have VHL illness should be closely monitored by a doctor or medical team who is experienced with the condition.