Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease caused by germline mutation in VHL tumor suppressor gene.
The disease, which was first described by Eugen von Hippel and Arvid Lindau in the 20th century, affects one in every 32,000 individuals in the US.
There is no specific treatment guideline followed to treat VHL syndrome. In general, long-term treatment procedure to treat the VHL syndrome can increase the risk of development of psychological disorders, which also induce somatic ailments. Therefore, VHL syndrome requires individualized treatment plan depending on the clinical features.
Effective management of the disease phenotypes depends on the size and location of the tumors. Due to the occurrence of tumors in multiple organs, establishing a comprehensive treatment strategy for VHL syndrome is complex. Thus, most of the interventions are basically related to a particular disease phenotype.
- In case of large and fast-growing hemangioblastomas, surgical removal of the tumor is the most recommended option. Besides surgery, non-invasive high dose radiotherapy such as stereotactic radiosurgery is another option to accurately target brain tumors.
- In cases of extensive spinal cord tumors, preoperative arterial embolization may be included as a part of disease management.
- Surgery is the most recommended option to remove adrenal gland tumors. Patients are generally recommended to take alpha-adrenergic and/or beta-adrenergic blockers for 7 to 10 days before the surgery to reduce the risk of high blood pressure induced by high catecholamine level during the surgery.
- The surgery generally involves complete or partial removal of the adrenal gland. In case of complete removal of the adrenal gland, patients are generally prescribed with hormonal therapy to fulfill the need of adrenal hormones.
- Partial removal of the adrenal gland is the choice of surgical intervention for pediatric patients.
- Minimally invasive laparoscopic surgery is also effective in some cases.
- Early diagnosis and treatment of retinal tumors are necessary to avoid vision loss. Xenon, diathermy, cryocoagulation and laser are different therapeutic intervention applied to treat the lesion. The selection of the process depends on the size and position of the lesion.
- In case the conventional method fails to provide success, then external beam radiotherapy is applied successfully to restrict the progression of the condition
Renal Cell Carcinoma
- Surgical removal of the fast growing or large kidney tumors (above 3 cm) is the best option to treat renal cell carcinoma, partial nephrectomy (partial removal of the kidney) or nephron-sparing. But this procedure can only be possible when the allowable size and preferable location of the tumor is suitable for conducting the process.
- Other options include radiofrequency ablation – treatment with radiofrequency waves to destroy tumors; and cryoablation – treatment with extremely cold probes to remove affected tissue.
- Radiofrequency ablation can be applied in case of smaller sized (<3cm) tumor. Laparoscopic and percutaneous radiofrequency ablation therapy have some tendency to provide complications, therefore frequent follow up is required.
- Cryoablation is widely used to avoid multiple surgical processes; it is also applied in case of small lesion.
- Renal transplantation is conducted in case of bilateral nephrectomy.
Pancreatic Cysts and Neuroendocrine Tumors
- Pancreatic cysts are generally harmless and do not require any surgical intervention. .
- Pancreatic endocrine tumors need constant follow-up because of their tendency to spread, as they cause malignancy). Surgical removal is recommended for a tumor larger than 3 cm or with a rapid growth rate
Given the complexity of VHL syndrome, individuals who are diagnosed with the disease; individuals with VHL pathogenic mutation but without any clinical manifestation; and at risk relatives who did not go through genetic testing require a close monitoring by healthcare professionals for better disease management. A routine surveillance protocol for VHL syndrome includes:
- Annual ophthalmic examinations starting at early childhood for the screening of retinal angioma
- Brain MRI in every 1-3 years starting at adolescence for the screening of CNS hemangioblastoma
- Abdominal MRI or ultrasound examination in every 12 months starting at the age of 16 years for the screening of kidney and pancreatic tumors
- Annual blood pressure monitoring and urine test for catecholamine metabolites for the screening of adrenal gland tumors
- Families with high risk for adrenal tumors, adrenal imaging and detection of plasma normetanephrine level starting from the age of 8 years are recommended.
About 80% of the patients with VHL syndrome have an affected parent; whereas, only 20% develops it through de novo mutations.
Genetic counseling, which includes proper medical explanations on the nature, inheritance, and implications of the disease to the affected or at risk parents, is an important approach to prevent disease transmission over generations. Molecular testing is recommended for parents of an affected individual to look for a mutation. If the pathogenic variant is not known, ophthalmic screening and abdominal ultrasound are other options that should be suggested to both parents.
Reviewed by Nita Sharma Das, PhD, ND