Von Hippel–Lindau disease

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Rare genetic disorder causing tumors in multiple organs


von Hippel–Lindau disease
Synonyms Familial cerebello-retinal angiomatosis, VHL syndrome
Pronounce N/A
Field N/A
Symptoms Headaches, dizziness, visual disturbances, limb weakness, balance problems, hypertension
Complications Vision loss, hearing impairment, renal failure, metastatic cancer, neurological deficits
Onset Typically young adulthood (20–40 years)
Duration Lifelong
Types N/A
Causes Mutation in the VHL tumor suppressor gene on chromosome 3p25.3
Risks Family history, autosomal dominant inheritance
Diagnosis Genetic testing, imaging (MRI, CT), ophthalmologic examination
Differential diagnosis Neurofibromatosis type 2, multiple endocrine neoplasia (MEN), polycystic kidney disease
Prevention Genetic counseling, regular surveillance screenings
Treatment Surgical removal of tumors, radiation therapy, targeted medical therapies
Medication Antihypertensives, targeted therapy for associated malignancies
Prognosis Variable; lifelong management required, favorable with early detection and treatment
Frequency 1 in 36,000 individuals worldwide
Deaths Primarily due to complications such as metastatic cancer or renal failure


Von Hippel–Lindau disease (VHL disease) is a rare, autosomal dominant genetic disorder characterized by the formation of tumors and fluid-filled cysts in multiple organs throughout the body. Tumors commonly occur in the central nervous system, kidneys, pancreas, adrenal glands, and eyes.

Signs and symptoms[edit | edit source]

Slit lamp photograph showing retinal detachment in von Hippel–Lindau disease.

Symptoms of VHL disease depend on tumor location, size, and organ involvement. Common presentations include:

  • Neurological symptoms:
    • Headaches
    • Dizziness
    • Problems with balance and walking (ataxia)
    • Limb weakness and numbness
    • Hearing impairment (due to endolymphatic sac tumors)

Associated conditions[edit | edit source]

VHL disease predisposes patients to develop multiple tumor types, including:

Genetics[edit | edit source]

Von Hippel–Lindau disease results from a mutation in the VHL tumor suppressor gene located on the short arm of chromosome 3 (3p25.3). The disease follows an autosomal dominant inheritance pattern, meaning an affected individual has a 50% chance of passing the mutation to offspring.

The VHL gene normally functions to suppress abnormal cell growth by regulating cellular oxygen sensing. Mutation or deletion of this gene leads to uncontrolled cellular proliferation and tumor formation.

Diagnosis[edit | edit source]

Diagnosis is established through clinical criteria, family history, and genetic testing:

  • Clinical evaluation: Detailed neurological, ophthalmological, and systemic examinations
  • Imaging studies:
    • MRI (brain, spine) to identify hemangioblastomas
    • CT/MRI abdomen to evaluate kidneys, pancreas, and adrenal glands
  • Genetic testing: Confirms VHL gene mutation, guides familial screening

Differential diagnosis[edit | edit source]

Conditions that must be distinguished from VHL disease include:

Management[edit | edit source]

There is no cure for VHL disease; management is focused on early detection, monitoring, and prompt treatment of tumors:

  • Surgical removal of symptomatic tumors or tumors at risk of malignancy
  • Radiation therapy for inaccessible or recurrent central nervous system tumors
  • Medical management: Control of hypertension (particularly due to pheochromocytomas), targeted therapies for renal cell carcinoma
  • Regular surveillance screenings:
    • Annual ophthalmologic examinations for retinal hemangioblastomas
    • Periodic MRI scans of brain and spine
    • Routine screening of kidneys, pancreas, and adrenal glands through imaging and laboratory tests

Prognosis[edit | edit source]

Prognosis depends on timely diagnosis, effective tumor management, and lifelong surveillance. With early detection and intervention, patients can have relatively normal life expectancy. Delayed diagnosis or inadequate management increases risk of severe complications, including vision loss, neurological deficits, metastatic renal cell carcinoma, and premature death.

Epidemiology[edit | edit source]

Von Hippel–Lindau disease is rare, with an estimated incidence of approximately 1 in 36,000 individuals globally. It affects men and women equally and typically becomes clinically apparent in early adulthood, though age of onset can vary widely.

History[edit | edit source]

VHL disease is named after ophthalmologist Eugen von Hippel, who first described retinal hemangioblastomas in 1904, and neuropathologist Arvid Lindau, who detailed central nervous system involvement and familial inheritance in 1927.

Research[edit | edit source]

Current research is focused on:

  • Improved genetic and molecular characterization of VHL mutations
  • Novel targeted therapies, including drugs targeting hypoxia-inducible factors (HIF) regulated by VHL
  • Gene therapy approaches to correct VHL gene defects

See also[edit | edit source]

External links[edit | edit source]

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Contributors: Prab R. Tumpati, MD