CENTRAL NERVOUS SYSTEM TUMORS IN VON HIPPEL-LINDAU MULTISYSTEM DISORDER: ARE THERE PREVENTIVE APPROACHES TO ESCAPE TUMOR INITIATION AT A YOUNG AGE?

Abstract In pediatric neuro-oncology, the likelihood of an underlying tumor predisposition condition should be considered for all types of brain tumors. The aim of this study was to report the dramatic history of a VHL Tunisian family with many affected adolescents presenting central nervous system hemangioblastomas among wich many died in their twenties and those who survived suffered from depression and suicide attempts. To provide optimal clinical care and genetic counseling to affected patients and their young relatives, we conducted a literature review to answer the major question for this family: are there any preventive approaches to escape tumor initiation in our at-risk relatives at young age? The onset of VHL syndrome at the index case of our Tunisian family was at the age of 40 years when she presented a blurred vision on the right, related to retinal angiomatosis. The evolution was caraterised by recurrent eye lesions, the development of multiple renal tumors and hemangioblastomas at the cerebral, cerebellar and cervical spinal cord levels with neurologic symptoms and various functional nervous sequels after neurosurgical resections. Familial features of VHL were present in half of her siblings (6 among 12). Her 2 adolescent sisters, dead at the age of 20, harbored cerebral hemangioblastomas, whereas 2 of her brothers who died respectively at the age of 21 and 47 years harbored respectively ocular angiomas and vertebral angiomas. A third 48 year-old alive brother harbored cerebral hemangioblastoma as well as renal cell carcinoma. Only preimplantation genetic diagnosis (PGD) to select unaffected embryos can be applied to prevent the disease. High-throughput methods such as microarrays and sequencing are available nowadays for late-onset disorders with genetic predispositions. Long term surveillance and timely preventive treatment of lesions are crucial for VHL disease carriers. Effective psychosocial support to vulnerable children and their families is also essential.