Von Hippel-Lindau (VHL) disease causes tumors and cysts to grow in multiple organs throughout the body, and its symptoms depend on where those growths develop. The disease affects roughly 1 in 36,000 people, with up to 87% of carriers showing signs by age 65. Because VHL can involve the brain, eyes, kidneys, adrenal glands, inner ear, and reproductive organs, the symptoms are wide-ranging and often appear gradually over years, sometimes starting in childhood.
Vision Problems From Retinal Tumors
Eye involvement is one of the most common and earliest signs of VHL. About half of all VHL patients develop retinal tumors (called retinal capillary hemangioblastomas), and these are frequently the first manifestation of the disease. The likelihood of developing a retinal tumor increases with age, reaching roughly 80% in patients over 80.
Small retinal tumors may cause no symptoms at all. As they grow, they can distort the retina’s structure and lead to blurred vision, floaters, or visual field loss. Larger tumors sometimes cause fluid buildup beneath the retina, leading to retinal detachment and significant vision loss. In rare cases, abnormal blood vessel growth in the iris or cornea can increase eye pressure and cause a painful type of glaucoma. Because these tumors can progress silently before symptoms appear, annual dilated eye exams starting at the time of diagnosis are recommended for VHL patients.
Brain and Spinal Cord Tumors
Around 45% of people with VHL develop hemangioblastomas in the central nervous system. These are slow-growing, noncancerous tumors made of dense blood vessels. They most commonly appear in the cerebellum (45% to 50% of cases), followed by the spinal cord (30% to 40%) and the brainstem (5% to 10%). Surveillance typically begins at age 11 with brain and spine MRI every two years.
The symptoms depend entirely on where the tumor sits. Cerebellar tumors tend to cause headaches, nausea, vomiting, difficulty with balance and coordination, unsteady walking, and trouble with fine motor tasks like buttoning a shirt. Some people notice involuntary eye movements.
Spinal cord tumors often produce localized back pain that may radiate along a nerve path into the arms or legs. Weakness in the limbs, numbness, tingling, and in some cases bladder or bowel dysfunction can follow. Brainstem tumors are less common but can affect cranial nerves, causing facial weakness, difficulty swallowing, double vision, and in severe cases, life-threatening bleeding within the brain.
Kidney Tumors and Cysts
Kidney involvement is one of the most serious aspects of VHL because it carries a risk of renal cell carcinoma, a type of kidney cancer. Multiple kidney cysts and solid tumors can develop, often in both kidneys simultaneously. Abdominal MRI surveillance is recommended starting at age 15, repeated every two years.
In early stages, kidney tumors and cysts rarely cause noticeable symptoms. As they grow, some people experience back or flank pain, blood in the urine, or a palpable mass in the abdomen. Because these tumors are often detected through routine surveillance before symptoms develop, many VHL patients learn about kidney involvement during a scheduled scan rather than from pain or other complaints.
Adrenal Gland Tumors
Pheochromocytomas are tumors of the adrenal glands that produce excess adrenaline and related hormones. They occur in a subset of VHL patients, and their symptoms tend to come in sudden, dramatic episodes called “spells.” During a spell, blood pressure can spike to dangerously high levels, sometimes reaching 250/110 or higher, before returning to normal between episodes.
Common symptoms during these spells include pounding headaches, heavy sweating, rapid heartbeat, and intense anxiety that can feel like a panic attack. Some people also experience trembling, chest pain, or a sense of impending doom. Between spells, a person may feel entirely normal, which can make the condition confusing to identify without proper testing. Annual biochemical screening for the hormones produced by these tumors is recommended starting as early as age 5 in children known to carry a VHL mutation.
Hearing Loss and Inner Ear Tumors
Endolymphatic sac tumors grow in the inner ear and can cause progressive, sometimes sudden, hearing loss. In VHL patients these tumors tend to appear at a younger age and grow more aggressively than in people without the syndrome. They have been diagnosed in VHL patients as young as 15.
The earliest and most common symptoms are ringing in the ears (present in about 92% of cases) and hearing loss (about 95%). Around 62% of patients experience vertigo or a sense of imbalance. The symptoms can closely mimic Ménière’s disease, with episodes of dizziness, a feeling of fullness in the ear, and fluctuating hearing. In some cases, bleeding within the inner ear causes sudden hearing loss. As the tumor grows, it can eventually affect the facial nerve, leading to weakness on one side of the face.
Pancreatic Cysts and Tumors
The pancreas is commonly involved in VHL, usually as simple cysts that cause no symptoms and require no treatment. However, some patients develop pancreatic neuroendocrine tumors, which are a more serious concern. Most pancreatic involvement is discovered incidentally during abdominal imaging done for kidney surveillance.
When pancreatic tumors do produce symptoms, they can include upper abdominal pain, nausea, or digestive problems. Functional neuroendocrine tumors (those that produce hormones) may cause blood sugar swings or heartburn, though this is uncommon in VHL-related cases.
Reproductive Organ Cysts
Up to 50% of men with VHL develop noncancerous tumors called cystadenomas in the epididymis, the coiled tube behind each testicle. These are often discovered as painless lumps during a physical exam, though some men experience scrotal pain or a feeling of pressure. Women with VHL can develop similar growths in the broad ligament near the uterus, though this is much less common. When present, broad ligament cystadenomas may cause pelvic pain or pressure but are often found incidentally during imaging for other reasons.
How Symptoms Vary by Genetic Type
Not every VHL patient develops the same set of tumors. The specific mutation in the VHL gene influences which organs are most at risk. VHL is broadly classified into two types. Type 1 carries a low risk of adrenal tumors but a higher risk of brain and spinal tumors, retinal tumors, kidney cancer, and pancreatic tumors. Type 2 is associated with a higher risk of adrenal tumors and is further divided: Type 2A has a low risk of kidney cancer, Type 2B has a high risk of kidney cancer, and Type 2C produces only adrenal tumors without involvement of other organs.
This variation means two people in different families with VHL can have very different experiences. Genetic testing can help identify which subtype a person carries, allowing doctors to tailor surveillance to the organs most likely to be affected.
When Symptoms Typically Appear
VHL-related tumors have been reported in children as young as 2, though this is exceptionally rare. In a study of children undergoing surveillance, the median age at first tumor diagnosis was 14.5 years, with a range of 11 to 17. Adrenal tumors were among the earliest to appear, diagnosed in some children at age 11. Retinal tumors and brain tumors followed, typically showing up in the mid-teens. By age 15, roughly 11% of mutation carriers have already developed a symptomatic tumor, and another 16% have tumors detectable on imaging but not yet causing symptoms.
Because many VHL tumors grow slowly and silently before producing noticeable problems, the disease is often diagnosed through surveillance rather than symptoms. For someone without a known family history, a diagnosis requires at least two VHL-related tumors. For someone with an affected first- or second-degree relative, a single VHL-related tumor is enough to confirm the diagnosis. Early genetic testing and structured screening remain the most effective way to catch tumors while they are small and treatable.