Von Hippel-Lindau

Question 1

What causes Von Hippel-Lindau?

Answer 1

Mutation in the VHL gene on SHORT arm of chromosome 3 leading to benign and malignant tumor growth.

It is an autosomal recessive disease that displays a dominant inheretance pattern.

Question 2

What are the major findings in Von Hippel-Lindau

Answer 2

Cysts everywhere.

Major causes of death are Renal Cell Carcinomas and CNS hemangioblastomas (blood vessel rich).

Question 3

How do you diagnose VHL disease?

Answer 3

One VHL lesion and family history

OR

2 VHL lesions

Question 4

What are the actions of VHL protein?

Answer 4

1. Regulate HIF (hypoxia induced TF)
2. Suppress aneuploidy
3. Stabilize microtubule

Question 5

Under normal conditions what happens to HIF?

Answer 5

HIf is hyrdoxylated and then VHL ubiquinates HIF. Hif is degraded.

Question 6

What happens to HIF under hypoxic conditions?

Answer 6

HIF is not degraded and goes and activates transcription of VEGF(vascular endothelial growht factor), TGF and PDGF.

Question 7

How can you distinguish between familial and sporatic VHL?

Answer 7

Familial is usually bilateral and earlier onset.