SNP Shot: Genomic Insights

Von Hippel-Lindau (VHL) syndrome is a genetic condition where tumors and fluid-filled cysts develop in various parts of the body. These growths can be benign (non-cancerous) or malignant (cancerous) and typically emerge in early adulthood, though symptoms can manifest at any age.

A hallmark of VHL syndrome is the presence of hemangioblastomas, tumors composed of new blood vessels. While usually non-cancerous, these can lead to serious health issues. Hemangioblastomas in the brain and spinal cord may cause symptoms such as headaches, vomiting, weakness, and difficulty with coordination (ataxia). They can also develop in the retina (the back of the eye), where they are known as retinal angiomas and can impair vision.

Individuals with VHL syndrome are prone to developing cysts in the kidneys, pancreas, and reproductive organs. They also face a higher risk of specific cancers, including clear cell renal cell carcinoma (a type of kidney cancer) and pancreatic neuroendocrine tumors.

VHL syndrome is also linked to pheochromocytomas, tumors that predominantly occur in the adrenal glands (small glands located atop the kidneys that produce hormones). Pheochromocytomas are generally benign. While they might not always cause symptoms, they can sometimes lead to headaches, panic attacks, excessive sweating, or dangerously elevated blood pressure that is resistant to standard treatment. These tumors pose a significant risk during stressful situations or trauma, such as surgery, accidents, or pregnancy.

Approximately 10% of individuals with VHL syndrome develop endolymphatic sac tumors, which are non-cancerous growths in the inner ear. These tumors can lead to hearing loss in one or both ears, ringing in the ears (tinnitus), and balance issues. If left untreated, they can result in sudden and profound deafness.

In some cases, non-cancerous tumors may also form in the liver and lungs of people with VHL syndrome, although these tumors often don't cause any noticeable symptoms.

Inheritance:

VHL syndrome is inherited in an autosomal dominant manner. This means that inheriting only one copy of a mutated VHL gene is enough to increase the risk of developing tumors and cysts. Most people with VHL syndrome inherit the mutated gene from a parent who has the condition. However, in roughly 20% of cases, the mutation occurs spontaneously during the formation of egg or sperm cells or very early in development. Unlike many autosomal dominant conditions, where one copy is enough to cause disease, VHL syndrome requires mutations in both copies of the VHL gene to trigger tumor and cyst formation. During a person's lifetime, a second mutation in the VHL gene happens in specific cells of organs like the brain, retina, and kidneys. Cells with two mutated copies of the gene are unable to produce functional VHL protein, which then allows tumors and cysts to develop. Almost all people who inherit one VHL mutation will eventually acquire a second mutation in some cells, which leads to the development of VHL syndrome.