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.
