Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Von Hippel-Lindau Syndrome

Also known as Von Hippel-Lindau disease of familial cerebello retinal angiomatosis.

What is Von Hippel-Lindau Syndrome?

• Von Hippel-Lindau syndrome (VHL syndrome) is a rare genetic disorder that affect multiple body systems
• Ophthalmologist Eugen von Hippel first recognized angioma in the eye of a patient in 1904
• Arvid Lindau recognized angiomas on the spine and cerebellum in 1927.
  • The term Von Hippel-Lindau syndrome was first used in 1936, but only came into common usage decades later
• Characteristics of the disorder include the appearance of visceral cysts and benign tumors
  • These tumors have the potential to transform into cancer
• VHL syndrome is classified as a type of phakomatosis
  • This is a group of rare syndromes that involve structures originating from embryonic ectoderm
• This disease can be categorized based on differences in clinical characteristics. These often correlate to the type of mutation present in the affected gene.
• While some patients are diagnosed at birth, others may be diagnosed late in life (60s-70s); average patient age at diagnosis is 26
• Incidence rate of VHL syndrome is 1 in 36,000 births

How Do You Get It?

• This disease is linked to mutations affecting the Von Hippel-Lindau tumor suppressor (VHL) gene.
  • This gene is found on the short arm of chromosome 3
• Over 1500 mutations on this gene have been attributed to VHL syndrome
• In most cases, VHL syndrome mutations are inherited; however, around 20 percent of cases are linked to ‘de novo’ mutations that are not linked to family history
• The VHL gene codes for the VHL protein, which regulates another protein called hypoxia inducible factor 1alpha
• Identifying tumors specific to the illness is a critical part of diagnosis

What Are The Symptoms?

• The presence of tumors are a major aspect of VHL syndrome
• Tumors and cancers commonly linked to the disease include:
  • Renal cell carcinoma
  • Pheochromocytoma
  • Hemangioblastoma
    • In people with a family history of the syndrome, the presence of one of these tumors or cancers is often sufficient for a diagnosis
• Commons signs and symptoms include:
  • High blood pressure
  • Vision problems
  • Headaches
  • Limb weakness
  • Difficulty with walking and balance
  • Dizziness
  • Cardiovascular disease
  • Stroke
  • Heart attack
• Other conditions and tumors can also be associated with VHL syndrome, such as:
  • Angiomatosis
  • Bilateral papillary cystadenomas
  • Hemangioblastoma
  • Endolymphatic sac tumor
  • Pancreatic cysts

How Is It Treated?

• There is no cure for VHL syndrome
• However, early recognition and treatment of the various manifestations of the disorder can make a significant difference in terms of enhancing quality of life and minimizing further complications.
• A big component of management is regular monitoring and screening for tumors and cancer
• Approaches for treatment include surgery, cryotherapy, and photocoagulation
• One drug, belzutifan, is currently being evaluated as a possible treatment for renal cell carcinoma associated with VHL syndrome.

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this condition from the VHL Alliance.