Von Hippel-Lindau disease

Alternate names

VHL syndrome; VHL; Von Hippel-Lindau disease; Von Hippel-Lindau syndrome

Definition

Von Hippel-Lindau (VHL) disease is an inherited disorder characterized by the abnormal growth of both benign and cancerous tumors and cysts in many parts of the body.

Cause

• Von Hippel-Lindau (VHL) disease is caused by a mutation in the VHL gene.
• This gene is a tumor suppressor gene, which helps to control cell growth.
• Mutations in the VHL gene lead to a lack of regulation of cell growth and survival, allowing cells to grow and divide uncontrollably.
• This contributes to the formation of the tumors associated with VHL disease.

Inheritance

• 

  Autosomal dominant pattern, a 50/50 chance.
• Mutations in the gene that causes VHL disease (the VHL gene) are inherited in an autosomal dominant manner. This means that having a mutation in only one copy of the VHL gene in each cell is enough to increase a person's risk of developing VHL disease.
• In most autosomal dominant conditions, having one mutated copy of the responsible gene is sufficient to cause the condition.
• However, in VHL disease, a mutation in the other copy of the gene must occur during a person's lifetime to trigger the development of VHL disease.
• For example, a person may inherit a mutated copy of the gene from a parent, but acquiring a second mutation in the other gene copy in a specific organ may trigger tumor development in that organ. Almost everyone who is born with one VHL mutation will eventually acquire a mutation in the second copy of the gene and develop VHL disease.
• In most cases, an affected person inherits the first mutated gene from an affected parent.
• However, in about 20% of cases, the mutation occurs for the first time in a person with no family history of the condition.
• This is called a de novo mutation.
• When a person with a mutation that can lead to VHL disease has children, each of their children has a 50% (1 in 2) chance to inherit that mutation.

Onset

Tumors usually first appear in young adulthood.

Signs and symptoms

• Symptoms of von Hippel-Lindau (VHL) disease vary among patients and depend on the size and location of tumors.
• Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia).
• Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina).
• These tumors, which are also called retinal angiomas, may cause vision loss.
• Pheochromocytomas affect the adrenal glands, which are small hormone-producing glands located on top of each kidney.
• These tumors often cause no symptoms, but in some cases they can produce an excess of hormones that cause dangerously high blood pressure.
• About 10 percent of people with VHL disease develop endolymphatic sac tumors, which are non-cancerous tumors in the inner ear.
• These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance.
• Individuals with VHL disease are also at a higher risk than normal for certain types of cancer, especially kidney cancer.
• Renal cell carcinoma occurs in about 70% of individuals with VHL disease by age 60 and is the leading cause of death.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Adrenal pheochromocytoma
• Cerebellar hemangioblastoma
• Elevated urinary catecholamines
• Hypertension
• Renal cell carcinoma(Cancer starting in small tubes in kidneys)
• Retinal capillary hemangioma

5%-29% of people have these symptoms

• Abdominal pain(Pain in stomach)
• Abnormal left ventricular function
• Anxiety(Excessive, persistent worry and fear)
• Back pain
• Cardiomyopathy(Disease of the heart muscle)
• Distal lower limb muscle weakness
• Elevated circulating catecholamine level
• Endolymphatic sac tumor
• Headache(Headaches)
• Hyperhidrosis(Excessive sweating)
• Hypertensive retinopathy
• Limb pain
• Macular edema
• Multiple renal cysts(Multiple kidney cysts)
• Pallor
• Palpitations(Missed heart beat)
• Pancreatic cysts
• Pancreatic islet cell adenoma
• Papillary cystadenoma of the epididymis
• Papilledema
• Stroke
• Upper limb muscle weakness(Decreased arm strength)
• Vertigo(Dizzy spell)
• Visual loss(Loss of vision)

1%-4% of people have these symptoms

• Epididymal cyst
• Increased intracranial pressure(Rise in pressure inside skull)
• Myocardial infarction(Heart attack)
• Myocarditis(Inflammation of heart muscle)
• Paraganglioma
• Polycythemia(Increased red blood cells)
• Retinal detachment(Detached retina)

Diagnosis

The diagnosis of von Hippel-Lindau disease can be made based on specific clinical criteria (signs and symptoms), or when molecular genetic testing reveals a change (mutation) in the VHL gene. Tests that may be used to establish a clinical diagnosis include:

• 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 (VHL) disease depends on the location and size of tumors.
• In general, the goal is to treat growths when they cause symptoms, but are still small so they don't cause permanent damage.
• Treatment usually involves surgical removal of tumors.
• Radiation therapy may be used in some cases.
• All people with VHL disease should be carefully followed by a physician or medical team familiar with the disorder.
• Intervention for most CNS lesions (remove brain and spinal lesions completely when large and/or symptomatic)
• Treat retinal (but not optic nerve) angiomas prospectively
• Early surgery (nephron-sparing or partial nephrectomy when possible) for renal cell carcinoma
• Renal transplantation following bilateral nephrectomy
• Remove pheochromocytomas (partial adrenalectomy when possible)
• Monitor pancreatic cysts and neuroendocrine tumors and consider removal of neuroendocrine tumors
• Consider surgical removal of endolymphatic sac tumors (particularly small tumors in order to preserve hearing and vestibular function)
• Cystadenomas of the epididymis or broad ligament need treatment when symptomatic or threatening fertility.[1].

NIH genetic and rare disease info

• NIH info on Von Hippel-Lindau disease

Von Hippel-Lindau disease is a rare disease.

Von Hippel-Lindau disease Resources
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