Center for Endocrinological Investigations (CEDIE), Hospital de Ninos R. Gutierrez, Buenos Aires, Argentina.
Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):401-13. doi: 10.1016/j.beem.2010.01.002.
von Hippel-Lindau disease (VHL) disease increases susceptibility to several malignancies, including renal cell carcinoma, haemangioblastomas of the central nervous system or retina and phaeochromocytomas. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation. In this review, we present a synopsis of clinical features of the disease and emphasise unique aspects of VHL syndrome in the paediatric population. Genotype-phenotype associations based on the risk of phaeochromocytoma have pointed to the existence of additional, HIF-independent functions of VHL that remain underexplored. We also examine the progress on these pleiotropic roles of VHL, which contribute to explain clinical features of VHL disease. These advances have important translational implications and are likely to offer a new host of therapeutic options to individuals affected by the disease in the future.
希佩尔-林道病（VHL）增加了多种恶性肿瘤的易感性，包括肾细胞癌、中枢神经系统或视网膜血管母细胞瘤和嗜铬细胞瘤。导致这种疾病的 VHL 肿瘤抑制基因，通过靶向缺氧诱导因子（HIF）转录因子进行降解，负责调节缺氧反应。在这篇综述中，我们总结了该疾病的临床特征，并强调了儿科人群中 VHL 综合征的独特方面。基于嗜铬细胞瘤风险的基因型-表型相关性表明，VHL 存在尚未充分探索的其他 HIF 非依赖性功能。我们还研究了 VHL 的这些多效性作用的进展，这些作用有助于解释 VHL 疾病的临床特征。这些进展具有重要的转化意义，并可能为未来受该疾病影响的个体提供一系列新的治疗选择。
