Points to Ponder for NEET-PG, FMGE & NEXT

VHL is an autosomal dominant disorder caused by mutations in the VHL tumor suppressor gene.
The main clinical features are hemangioblastomas (cerebellum, spine, retina), renal cysts and clear cell RCC, and pheochromocytomas.
Regular screening with abdominal ultrasound, brain MRI, urinary VMA, and ophthalmoscopy is essential for early detection and management.

Genetic Basis:

Autosomal dominant inheritance.
Mutation in the VHL gene located on chromosome 3.
The VHL gene codes for the VHL tumor suppressor protein, which regulates cell growth and angiogenesis (blood vessel formation).

Clinical Manifestations:

Can involve various organ systems due to benign (hemangioblastomas) and malignant (carcinomas) tumors.

Hemangioblastomas: Benign, slow-growing tumors with many blood vessels. Can occur in various locations:
- Cerebellum (most common site)
- Spinal cord
- Retina (causing vision problems)
Renal cysts and clear cell renal cell carcinoma (RCC):
- Multiple renal cysts are frequent.
- Increased risk of developing bilateral (both kidneys) clear cell RCC, a malignant kidney cancer.
Pheochromocytomas: Tumors of the adrenal glands that produce catecholamines (hormones) and can cause high blood pressure, headaches, sweating, and palpitations.

Screening and Surveillance:

Early detection and management are crucial due to the potential for malignancy (RCC) and complications from other tumors. A regular screening protocol is recommended:

Annual abdominal ultrasound: To monitor for renal cysts and RCC development.
Baseline brain MRI at 20 years old and annual neurological examination: To detect hemangioblastomas in the brain and spinal cord.
Annual measurement of urinary metanephrines (VMA): To screen for pheochromocytomas.
Annual ophthalmoscopy: To check for retinal hemangioblastomas.

Management:

Treatment depends on the location, size, and symptoms of the tumors.
Options include surgery, radiation therapy, targeted medications (e.g., mTOR inhibitors for RCC), and watchful waiting.
Genetic counseling is recommended for affected individuals and family members.