Launbjerg Karoline, Bache Iben, Galanakis Michael, Bisgaard Marie Luise, Binderup Marie Louise M
Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark.
Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
Am J Med Genet A. 2017 Sep;173(9):2381-2394. doi: 10.1002/ajmg.a.38324. Epub 2017 Jun 26.
The autosomal dominant von Hippel-Lindau disease (vHL) is associated with a lifelong risk of tumor development, especially retinal and CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma. Knowledge of paediatric vHL development is limited, and current surveillance guidelines are based on expert opinions. We aimed to describe the course of vHL development in children and adolescents, focusing on age at first manifestation, manifestation frequencies, and types. The prevalence of vHL diagnosis as well as manifestations in childhood were evaluated based on 99 patients, who had started surveillance before 18 years: 37 Danish patients from the national vHL research database and 62 international patients reported in 15 articles. Overall, 70% (69 of 99) developed manifestations before 18 years (median age at first manifestation: 12 years (range: 6-17 years)). Thirty per cent (30 of 99) had developed more than one manifestation type; the most frequent were retinal (34%) and CNS (30%) hemangioblastomas. Among the 37 Danish patients, 85% (97 of 116) of their tumors were asymptomatic. Vision outcome is significantly improved in hemangioblastomas that are treated while still asymptomatic. We agree with current guidelines that retinal surveillance be performed from birth. The patients had their first CNS hemangioblastomas at the median ages of 13-14 years (range: 6-17 years). Further, 11% (4 of 37) of the Danish patients had CNS surgery in their teenage years. Although the cohort is too small to make definite conclusions about specific initiation ages, regular CNS surveillance from vHL patients' teenage years seems clinically relevant.
常染色体显性遗传性希佩尔-林道病（vHL）与终生肿瘤发生风险相关，尤其是视网膜和中枢神经系统血管母细胞瘤、嗜铬细胞瘤和肾细胞癌。关于儿童vHL的发展情况了解有限，目前的监测指南基于专家意见。我们旨在描述儿童和青少年vHL的发展过程，重点关注首次出现症状的年龄、症状出现频率和类型。基于99例18岁前开始监测的患者评估了vHL诊断的患病率以及儿童期的症状表现：37例来自国家vHL研究数据库的丹麦患者和15篇文章中报道的62例国际患者。总体而言，70%（99例中的69例）在18岁前出现症状（首次出现症状的中位年龄：12岁（范围：6 - 17岁））。30%（99例中的30例）出现了不止一种症状类型；最常见的是视网膜（34%）和中枢神经系统（30%）血管母细胞瘤。在37例丹麦患者中，85%（116例中的97例）的肿瘤无症状。在无症状时接受治疗的血管母细胞瘤患者的视力预后有显著改善。我们赞同当前从出生就进行视网膜监测的指南。患者首次出现中枢神经系统血管母细胞瘤的中位年龄为13 - 14岁（范围：6 - 17岁）。此外，11%（37例中的4例）丹麦患者在青少年时期接受了中枢神经系统手术。尽管该队列规模太小，无法就特定的起始年龄得出明确结论，但从vHL患者青少年时期开始进行定期中枢神经系统监测在临床上似乎是有意义的。
