Purpose

Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients.

Methods

We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed.

Results

42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2–17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9–7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2–8.9, p = 0.02) compared with missense mutation carriers.

Conclusion

We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins.

German clinical trials Register registration number

DRKS00029553, date of registration 08/16/2022, retrospectively registered.

中文翻译：

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冯·希佩尔-林道病儿科患者中枢神经系统血管母细胞瘤的筛查和监测建议

目的

Von Hippel-Lindau (VHL) 病是一种常染色体显性遗传的肿瘤易感综合征。最常见的肿瘤之一是中枢神经系统（CNS）血管母细胞瘤。关于启动和继续儿童 VHL 患者中枢神经系统肿瘤筛查和监测计划的建议是基于小病例系列，因此证据水平较低。为了得出更可靠的筛查建议，我们报告了最大的单中心儿科 VHL 患者队列。

方法

我们对 1992 年至 2023 年在我们的 VHL 中心就诊的 99 名 VHL 患者的儿科队列进行了回顾性分析。收集了临床、手术、遗传和影像数据并进行了统计分析。

结果

42 名患者（50% 男性）出现中枢神经系统血管母细胞瘤，其中 18 名患者（56% 男性）接受了血管母细胞瘤手术（首次手术平均年龄：14.9 ± 1.9 岁；范围 10.2–17）。第一位无症状患者因肿瘤进展在13.2岁时接受了手术。与错义突变携带者相比，截短VHL突变携带者的表现率（HR = 3.7，95% CI：1.9-7.4， p  < 0.0001）和手术率（HR = 3.3，95% CI：1.2-8.9，p  = 0.02）显着更高突变携带者。

结论

我们建议从 12 岁开始进行 MRI 成像，根据中枢神经系统受累情况，每 (1-) 2 年检查一次。应特别注意截短变异的患者。应定期对受影响的家庭进行有关潜在肿瘤相关症状的教育，以便及时进行 MRI 成像并最终进行干预，因为中枢神经系统血管母细胞瘤可能在筛查开始之前出现。

德国临床试验注册登记号

DRKS00029553，注册日期2022年8月16日，追溯注册。