VON HIPPEL-LINDAU DISEASE


I. Definitions and epidemiology

  1. Autosomal dominant inheritance; near 100% penetrance but varying clinical features
  2. Unknown prevalence as of 1994 but rare
  3. Unknown pathogenesis but seems to involve loss of a tumor-suppressor gene on the short arm of chromosome 3; according to the "two hit" theory of carcinogenesis, you then need to lose only one copy of that gene in any somatic cell to develop one of the characteristic neoplasms

II. Clinical Features: diagnosis requires one from group A plus one from group B or two from group A or a family hx of VHL and one from either group (Melmon KL and Rosen SW. Am. J. Med 36:595, 1964)

  1. Retinal angioma(s) (treatment with photocoagulation or cryotherapy can prevent blindness
  2. Cerebeller hemangioma(s) (benign; not responsive to XRT; resected only if symptomatic?)
  3. Spinal hemangioma(s)
  1. Pheochromocytoma
  2. Renal cell carcinoma (most common cause of death)
  3. Renal cysts (frequently premalignant)
  4. Pancreatic cysts (usually not premalignant)
  5. Epididymal cysts

III. Diagnosis

  1. Some genetic testing is available?
  2. Important to screen all close (e.g. first-degree) family members of any cases
  3. Proposed surveillance protocol for first-degree relatives of cases
  1. Education and counseling
  2. Annual hx/px from age 10y
  3. Annual ophthalmologic exam from age 6y
  4. Urinary testing for pheochromocytoma once
  5. MRI of posterior fossa every 10y after age 20
  6. Ultrasound AND CT of kidneys/pancreas every 10y after age 15-20
  1. Proposed surveillance protocol for pts with VHL
  1. Education and counseling
  2. Annual hx/px from age 10y
  3. Ophthalmologic exam Q6-12mo from age 6y
  4. Urinary testing for pheochromocytoma once
  5. MRI of posterior fossa every 1-5y after age 15-20
  6. Ultrasound (inadequate to distinguish renal cysts from Ca) AND CT of kidneys/pancreas every 1-5y after age 15-20
  7. Bilateral selective renal angiography every 1-5y after age 15-20
  1. In addition, above screening tests are indicated whenever suggestive sx occur

(Source: AFP 50:1269, 1994)