The Genetic and Clinical Aspects of Von Hippel-Lindau Syndrome

Von Hippel-Lindau syndrome is a genetic disorder, which predisposes the individual to the formation of highly vascularized tumors that demonstrate age dependent penetrance. The disease is caused by mutations in Von Hippel-Lindau tumor suppressor gene present in short arm of chromosome 3. The disease is characterized by development of CNS hemangioblastomas, phaeochromocytoma, renal cyst, clear cell renal cell carcinoma. The Diagnosis of VHL can be made in a patient with confirmed family history using molecular genetic testing of the VHL gene and presence of tumor. Average life expectancy in patients with VHL has been about 50 years. The protein products encoded by VHL gene recognize and destroy α-subunit of Hypoxia inducible factor. Cells lacking functional VHL protein accumulates HIF-α which up regulate hypoxia responsive genes. These genes products include proteins that control glucose uptake and metabolism, extracellular pH, growth factors, which regulate vascular development, angiogenesis, and lymphangiogenesis by binding to its receptor. Hence, VHL is a tumor suppressor gene based on both genetic and functional criteria, and VHL inactivation appears to be a very early step in renal carcinogenesis. VHL disease is classified into type 1 and type 2 depending on the phenotype but it is only helpful for research studies. The treatment of patient with VHL depends upon the specific complications of the disease present. Screening is recommended from childhood once diagnosis has been established. CNS hemangioblastomas are the most common manifestation, detailed neurologic history, CNS examination and baseline brainstem and spine MRIs should be done for any symptomatic conditions. Opthalmoscopic screening from early childhood and yearly follow-ups to prevent visual impairment. Audio logic tests and MRI auditory canal should be done when symptomatic for endolymphatic sac tumors. Blood pressure evaluations and yearly urinary catecholamines level for pheochromocytoma. Abdominal ultrasound screening should be started at 8 years of age; any abnormality should be evaluated by CT or MRI. Dow University of Health Sciences, Karachi, Pakistan *Corresponding author: Hira Burhan, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi 74200, Pakistan, Tel: +92 332 3587197; E-mail: [email protected] Citation: Burhan, H., et al. The Genetic and Clinical Aspects of Von Hippel-Lindau Syndrome. (2018) Int J Hematol Ther 4(1): 17. Received date: August 27, 2017 Accepted date: January 25, 2018 Published date: January 31, 2018