Von Hippel-Lindau (VHL): Understanding and Management

How Von Hippel-Lindau syndrome affects the body

VHL can involve multiple organs. The most common tumour types seen in people with VHL include:

• Hemangioblastomas in the brain, spinal cord, and retina
• Clear cell renal cell carcinoma and kidney cysts
• Phaeochromocytomas affecting the adrenal glands
• Pancreatic cysts and pancreatic neuroendocrine tumours
• Inner ear tumours (endolymphatic sac tumours)
• Reproductive system tumours

Symptoms vary depending on where tumours develop and may include headaches, vision changes, dizziness, high blood pressure, or abdominal pain.

For people with VHL, neuroendocrine cancer care is particularly relevant because it can increase the risk of pancreatic neuroendocrine tumours (pNETs) and adrenal tumours.

Genetic causes and inheritance of VHL

VHL syndrome follows an autosomal dominant inheritance pattern, meaning:

• Only one altered copy of the gene is needed to develop the condition
• Each child of an affected parent has a 50% chance of inheriting it

Around 20 percent of cases occur due to a new spontaneous mutation with no family history.

The VHL gene normally acts as a tumour suppressor by controlling oxygen-related cellular pathways. When mutated, proteins linked to abnormal blood vessel formation accumulate, allowing tumours to grow.

Because of this genetic basis, families affected by VHL will benefit from genetic counselling and testing.

Common tumour types and symptoms of VHL

Hemangioblastomas of the brain and spinal cord

These vascular tumours can cause:

• Headaches
• Balance or coordination problems
• Weakness or sensory changes

Retinal hemangioblastomas

Growths in the eye may lead to blurred vision or vision loss if untreated.

Kidney tumours and cysts

Clear cell renal cell carcinoma is one of the most serious complications of VHL and requires careful surveillance.

Endocrine tumours

Phaeochromocytomas may produce excess adrenaline, causing:

• High blood pressure
• Palpitations
• Sweating
• Anxiety

Pancreatic tumours and NETs

Pancreatic cysts and neuroendocrine tumours can develop for people with VHL.

How von Hippel-Lindau syndrome is diagnosed

Diagnosis usually combines clinical evaluation with genetic testing.

Doctors may suspect VHL when:

• Multiple characteristic tumours are present
• There is a family history of VHL
• A single typical tumour appears in a young patient

Diagnostic tools often include:

• MRI scans of the brain and spinal cord
• Retinal eye examinations
• Abdominal imaging
• Blood pressure monitoring
• Genetic testing for VHL gene mutations

Because symptoms can overlap with other conditions, specialist evaluation is essential.

Lifelong surveillance and monitoring

Unlike many cancers, management of VHL focuses heavily on regular surveillance rather than one-time treatment.

Monitoring may include:

• Annual or regular MRI scans
• Eye and ear examinations
• Blood pressure checks
• Kidney and pancreatic imaging

Early detection allows tumours to be treated before they cause serious complications. Many patients follow personalised screening schedules designed by specialist teams.

Treatment options for Von Hippel-Lindau syndrome

There is currently no cure for VHL. Treatment aims to manage individual tumours and prevent complications.

Surgery

Surgical removal is often used when tumours grow large, cause symptoms, or show signs of becoming malignant.

Interventional radiology

Minimally invasive techniques such as cryoablation or radiofrequency ablation may treat kidney or pancreatic lesions.

Medical therapies

Targeted medications are becoming more common in VHL care. Drugs such as HIF-2α inhibitors (for example Belzutifan) aim to control tumour growth by targeting the underlying genetic pathway.

Supportive treatments

Medications may help manage symptoms like hypertension caused by pheochromocytomas.

Clinical subtypes of VHL

Doctors sometimes classify VHL into subtypes based on tumour risk:

• Type 1: Higher risk of hemangioblastomas and kidney cancer, lower risk of phaeochromocytoma
• Type 2A: Higher risk of phaeochromocytoma, lower kidney cancer risk
• Type 2B: Higher risk of both kidney cancer and phaeochromocytoma
• Type 2C: Primarily phaeochromocytoma risk

Understanding subtype patterns helps guide screening and surveillance strategies.

Emerging research and future treatments

Advances in genetic research are transforming how VHL is managed.

Key areas of progress include:

• HIF-2α inhibitors designed to target the biological pathway affected by VHL mutations
• Precision medicine approaches that aim to reduce repeated surgeries
• Early-stage research into gene-editing technologies

While many therapies are still evolving, these developments offer hope for more personalised treatment in the future.

Living with Von Hippel-Lindau syndrome

Living with VHL can be physically and emotionally demanding. Many people require lifelong monitoring, repeated scans, and ongoing decision-making around treatment.

Helpful strategies include:

• Building relationships with specialist multidisciplinary teams
• Seeking psychological and peer support
• Staying informed about surveillance schedules
• Maintaining open communication with healthcare providers

Because VHL symptoms may change over time, ongoing support is essential for both patients and families.

Support and resources through NeuroEndocrine Cancer Australia

NeuroEndocrine Cancer Australia (NECA) provides education, support, and guidance for people affected by VHL, particularly those with neuroendocrine tumours.

Support may include:

• Access to a national NET Nurse service
• Education about pancreatic NETs linked to VHL
• Help navigating complex treatment pathways
• Information and assistance finding to multidisciplinary specialists experienced in VHL via the VHL Specialist Register.

If you or someone you care for has been diagnosed with VHL or a related neuroendocrine cancer, contacting NECA can help you better understand your options and access tailored support.

Find resources, support and clinicians for patients dealing with Von Hippel-Lindau Syndrome.