Von Hippel-Lindau disease: Year of the Zebra 2024

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Von Hippel-Lindau, or VHL, disease is a genetic disorder characterized by tumor development in many different organs, like the central nervous system, including the eyes; kidneys; adrenal glands; and pancreas.
It’s caused by a mutation in a tumor suppressor gene found in chromosome 3. Tumor suppressor genes code for proteins that regulate the cell cycle, preventing cells from growing out of control.
When a tumor suppressor gene gets turned off, like in VHL disease, cell growth goes unchecked, allowing cells to keep dividing uncontrollably, increasing the risk of tumor formation.
The VHL mutation is inherited in an autosomal dominant pattern, meaning only one copy of the mutation causes disease, and individuals have a 50% chance of passing the mutation to their offspring with each pregnancy.
However, some people have what’s called a new, or de novo, mutation, where the mutation occurs randomly and is not inherited.
The most common and characteristic type of tumor in VHL disease is hemangioblastoma, a benign blood vessel tumor that typically develops in the brain, spinal cord, and retina in the eye.
Even though they are benign, hemangioblastomas can cause symptoms if they push against surrounding tissues. For example, if the tumor is in the cerebellum, it can cause loss of balance; whereas in the eyes, it can cause blindness.
Another benign tumor is pheochromocytoma, a tumor of the adrenal glands that can cause symptoms like headaches, sweating, palpitations and increases in blood pressure due to the release of adrenal hormones.
Some people also develop cyst-like tumors in the liver, lungs, kidneys and pancreas, as well as near the uterus or testicles.
Finally, some tumors associated with VHL disease are cancerous, such as renal cell carcinoma, a malignant tumor that can affect both kidneys and metastasize quickly.
Not every person with VHL disease will have every type of tumor, but they will almost always develop at least one. On average, most individuals develop their first tumor by their mid-twenties, but the age of onset varies with the type of tumor.
Now, VHL disease may be suspected in people who present with several VHL-related tumors throughout their life. Since VHL disease can be inherited, the first step in the diagnosis is to obtain a detailed family history in addition to a personal history and physical exam.
Imaging tests like an MRI can be used to detect brain and spinal cord tumors, while an abdominal CT scan may be used for detecting tumors in the kidneys, adrenal glands, and pancreas.
Genetic testing can help confirm the diagnosis and is even recommended for those with a family history of VHL disease, as it can help identify the VHL mutation in those that may not yet have symptoms.
Part of the treatment of VHL disease involves regular surveillance to detect significant tumors as soon as possible, and this may involve periodic MRIs, CT scans, ultrasounds, and ophthalmologic exams.
Treatment recommendations are designed to preserve organ function, since new tumors can develop repeatedly in the same organs, even after receiving treatment.
Depending on the tumor type, treatment may involve surgery, or targeted therapies, which aim to stop the growth of tumor cells.
Finally, options like preimplantation genetic testing are available for individuals who wish to have children without the risk of passing on the mutation.
Alright, as a quick recap… von Hippel-Lindau disease is a genetic condition that causes tumors in many different organs, like the central nervous system, including the eye; kidneys; adrenal glands; and pancreas.
Most of these are benign tumors, but they also have the potential to be malignant such as renal cell carcinoma. Routine screening and early intervention are crucial as tumors can develop repeatedly throughout a person’s lifetime, even after receiving treatment.