Von Hippel-Lindau disease is a rare genetic disorder that is characterized by the manifestation of tumors and cysts in different parts of the body. VHL is a rare and incurable disease that occurs in 1 in every 36,000 people. This disease is an autosomal dominant genetic condition that results when there is an alteration (mutation or deletion) of the VHL gene that is found on chromosome 3. Although very uncommon, symptoms of VHL skin manifestations include capillary malformations (port-wine stain).
Von Hippel Lindau Disease – A Brief Overview
For almost all cases of VHL, the pattern of autosomal dominant inheritance occurs, meaning that the altered version of the vHL gene was passed down from one parent. VHL syndrome occurs when there is a deletion or mutation of the VHL tumor suppressor gene on chromosome 3. This impairs the gene’s ability to control the pVHL (VHL protein), or a defective pVHL is produced, reducing, or removing the protein’s ability to control or prevent the growth of tumors. Symptoms generally present in early childhood or adolescence.Read More
“In Von Hippel-Lindau disease, we also see a good proportion of what we call de novo mutation, so meaning you are the first one in the family, it just happened during development or prior to fertilization at some point, but you are just the first one,” Dr. Tobias Else told SurvivorNet.
In about 20% of cases, patients are first-in-family, or de novo cases, where the is no family history of vHL, and the genetic mutation is present for the first time. The most conclusive way of diagnosing Von Hippel-Lindau is by genetic testing (blood test or finger prick). Genetic tests allow for, in the case of de novo cases, to confirm VHL diagnosis by matching the gene alteration against a database.
The types of tumors that are generally related to VHL include:
- Endolymphatic sac tumors (benign tumors in the inner ear)
- Kidney cysts and clear renal cell carcinoma
- Hemangioblastomas (tumors in the central nervous system and the most common tumor seen in vHL)
- Pancreatic neuroendocrine tumors
- Pheochromocytomas (Benign tumors in the adrenal glands)
- Papillary cystadenomas of the epididymis and broad ligament
The symptoms of VHL depend on where the tumors grow in the body, their size, and the type of tumor. When these tumors and cysts (both malignant or benign) occur in the body, they can cause:
- If a hemangioblast grows in the retina, the patient’s vision could be affected due to pressure being placed on the tissue that lines the back of the eye.
- High blood pressure, nausea, changes in vision, clammy skin, pallor (turning pale), racing heartbeat, palpitations, and sweating from tumors of the adrenal gland (pheochromocytoma).
- Hematuria (blood in the urine) from renal cell carcinoma (kidney cancer).
Von Hippel- Lindau Dermatological Manifestations
Capillary malformations are commonly called port-wine stains, and they occur due to a type of disorder of the vascular system (made of the blood and lymph vessels in the body). They are noncancerous and present as purple or red skin discolorations. They are not hemangiomas but instead are malformed diluted blood vessels in the skin.
In VHL, the “port-wine stain” forms as there are enlarged clustered capillaries that have a single layer of endothelium and do not have a mature vessel wall (attributes to the ‘free-form’ shape). They may vary in size and darkness of color and can be found anywhere on the body.
Café-au-lait spots that are usually associated with neurofibromatosis (tumors of the nerve tissue) can very rarely present in VHL patients. Café-au-lait spots are characterized by light to dark brown pigmented spots that are most frequently observed on a newborn’s skin. These pigmented spots can also develop and occur during childhood and adulthood.
Symptoms of VHL Dermatological Manifestations
The capillary malformations form most commonly on the head and neck area, but they can be found elsewhere on the patient’s body. They are generally present with no symptoms (asymptomatic) other than the patient having a visible red or purple “birthmark.” Café-au-lait spots are asymptomatic and can be found anywhere on the individual’s body.
Dermatological Manifestation Diagnosis
Diagnosis of capillary nevi can be made by your doctor during a physical exam or when you are born. If your doctor is concerned about an underlying disease or if underlying tissue is damaged, an ultrasound scan is often used. Café-au-lait spots are diagnosed by a doctor during a physical exam, either at birth or during young childhood.
Treatment and Prevention for VHL Skin
The dermatologic manifestations of VHL do not need treatment as they are noncancerous (benign) and do not cause symptoms (asymptomatic). There are options to remove café-au-lait spots and capillary malformations for cosmetic reasons – this is achieved with laser treatment.
Laser treatment is the most effective treatment in successfully removing capillary malformations and café-au-lait spots. For the removal of capillary malformations, the pulsed dye laser (PDL) is the most successful. It may take a couple of laser treatments to achieve noticeable results.
Laser treatment does carry some risk of hyperpigmentation (scarring), as the spot or birthmark may return if the pigmentation does not clear. Capillary malformations may also bleed after minor trauma (such as laser treatment).
In very rare cases of capillary malformation (complex and severe syndromes), the treatment measures taken by specialists are discussed.
There are minimal risk factors for VHL dermatological manifestations and do not cause further symptoms but may rather alert to an underlying condition such as VHL. There is no way to reduce the risk of getting café-au-lait spots, or capillary malformations, as there is no way to prevent them.
Questions To Ask Your Doctor
- Will a tumor grow where I have a dermatological manifestation?
- Does having a capillary malformation or café-au-lait spots increase my risk of getting a tumor?
- Will the dermatological manifestation disappear on its own over a period of time?
- Are there treatment options for VHL skin?
- Check out the VHL Alliance – a great resource for patients and families looking for more information on VHL.
The Bottom Line
Dermatological manifestations (skin lesions) present in von Hippel-Lindau disease are noncancerous and asymptomatic, with only 5% of vHL cases presenting with a “birthmark.”
Dr. Craig Rogers, Chair of Urology, Henry Ford Health, and head of von Hippel-Lindau Clinical Care Center told SurvivorNet that many patients with the disease lead full lives.
“There are plenty of patients that do that now because of close monitoring, picking it up early, medications. Some patients live a very long time with this,” he explained.
Depending on the size and color of the skin lesion, cosmetic treatment options such as laser treatments may be sought out or consulted with your doctor. If you have any concerns that there might be underlying conditions, if you suddenly start presenting with skin lesions, or you are concerned that your skin lesions point to further symptoms in your vHL, it is important to consult your doctor.
If you would like any additional support, VHL Alliance provides a comprehensive list of resources to connect you with a support group. If you would like to know more about your VHL, SurvivorNet has in-depth resources to help you understand your journey with VHL.