Von Hippel-Lindau disease

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 1, 2016
StartDiseasesVon Hippel-Lindau disease

Von Hippel-Lindau disease (VHL) or von Hippel-Lindau syndrome is a rare disorder caused by a genetic mutation that has the potential for causing multiple cysts or benign tumors anywhere in the body. The abnormal growths also carry a likelihood of transforming into malignant tumors or cancer.

Contents

Definition & Facts

Approximately one out of every 36,000 people are born with the disorder. VHL equally affects females and males of all ages and is not more prevalent among one ethnic background or country of origin over another.

The cysts or tumors may develop in one isolated area or simultaneously in up to 10 different regions of the body. Commonly affected regions include the adrenal glands, brain, ears, eyes, kidney, liver, spine, and urogenital tract.

The cysts, tumors or other growths caused by the genetic anomaly commonly involve abnormal blood vessels. In their benign form, the growths remain restricted to one organ location. However, if malignancies develop, the cells may metastasize or travel through the blood or lymphatic system and create new tumors in other areas of the body.

Symptoms & Complaints

Symptoms are related to where the location of the tumors are present and vary depending on how the anomaly affects a particular organ. In some instances, the syndrome may exist for years before detection.

If multiple family members inherit von Hippel-Lindau, one person may not experience symptoms while another may suffer serious illness. The age of onset when problems first appear also varies from one person to the next.

Hemangioblastomas (a type of hemangioma) or angiomas are among the common types of malformations caused by VHL. The benign growths often develop in the brain, spinal cord, or on the retina at the back of the eye. They look similar to knotted blood vessels and though harmless, they often put pressure on surrounding tissues, which causes symptoms.

When formed in the brain, a patient may experience headaches, nausea, and vomiting, difficulties with balance when standing or walking or a generalized weakness in the arms and legs.

In the eyes, angiomas commonly leak blood or fluid, which causes increased pressure within the eye and subsequent light sensitivity, visual disturbances, and eye pain. If the growths develop in the ear, they may cause continual ringing in the affected ear tinnitus), hearing loss, and balance problems due interference with the function of the vestibular system.

Some patients afflicted with the syndrome develop adrenal gland tumors known as pheochromocytomas. Symptoms related to the location of these growths involve an increase in adrenaline levels. Patients commonly suffer from high blood pressure, an elevated heart rate (tachycardia), have difficulty breathing, and sweat profusely. Individuals might also complain of headaches, have involuntary shaking or tremors.

If VHL anomalies develop on a kidney, there is a 40 percent chance that the growth becomes malignant. The chances of cancer development increase as a patient gets older. Pancreatic cysts may also evolve into cancer.

Causes

The syndrome occurs when changes or mutations occur in one or both copies of what is known as the VHL gene. Everyone inherits one gene from each parent. If one parent passes a mutated gene, the child has a 50 percent chance of having von Hippel-Landau syndrome.

Some people never develop symptoms but still have the ability to pass a mutated gene to their offspring. About 20 percent of the people afflicted with VHL do not inherit the gene. For unknown reasons, the gene develops the mutation, and they become the first in their family to carry the mutation or develop the disorder.

Diagnosis & Tests

The types of tests ordered for patients having no family history of von Hippel-Lindau syndrome depend on the complaints or symptoms that an individual experiences. Physicians arrive at a positive diagnosis if the patient has more than two hemangioblastomas in the brain, retina or spine. They might also have tumor growths or multiple cysts in the kidney or pancreatic region.

In patients having a family history of the disorder, physicians evaluate for retinal angiomas, brain or spinal hemangioblastomas, adrenal pheochromocytomas, renal-cell carcinoma or multiple kidney or pancreatic cysts.

Treatment & Therapy

As the disease process varies between each affected individual, physicians offer treatment options based on the evaluations of the individual patient. Symptoms, medical imaging studies, blood test results and the person's overall physical condition are all considered before determining the best course of action.

Hemangioblastomas in the brain or spinal column are typically surgically removed. If any portion of the tumor remains, the cysts generally recur. Under some circumstances, smaller lesions that are not causing active symptoms are treated using stereotactic radiosurgery (a type of radiation) as a preventative measure.

When it comes to treating ear tumors or endolymphatic sac tumors, surgical removal is recommended to prevent further complications if they appear on a magnetic resonance imaging (MRI) scan or the patient experiences hemorrhaging. Surgery is also advised for patients suffering hearing loss, having visible ear lesions or problems with physical balance.

Treating pancreatic neuroendocrine tumors. A detailed analysis is used to determine the difference between pancreatic cysts and tumors. Cysts on the pancreas or adrenal glands are not often treated. Tumor treatment options depend on the location, size, growth rate and DNA type of the cells.

Pheochromocytomas, which are tumors on the adrenal glands are removed after the patient undergoes medication therapy to inactivate the gland. Vital signs are also carefully monitored during this time. Surgical removal of the mass is usually recommended regardless of whether the tumor is growing or causing symptoms.

Von Hippel-Lindau tumors on the kidney are often found in the early stages of development and closely monitored. Surgical removal is only recommended when the growth rate and size of the mass indicate that there is a potential for metastasis, which is approximately three centimeters. Non-surgical options include cryotherapy or radiofrequency ablation.

Retinal hemangioblastomas, which are small lesions, are often treated without adverse effects using laser surgery. Physicians may opt to use cryotherapy for larger lesions. If the growth develops on the optic disc, the chances of preserving the patient's vision decreases.

Prevention & Prophylaxis

For families with a history of von Hippel-Lindau, adults and children can be genetically tested for the genetic mutation using a simple blood test. If the test is positive, the affected individual must undergo routine screenings, which include: