Département de Médecine Génomique des Tumeurs et Cancers/UF Oncogénétique Tumeurs et Cancers Rares, AP-HP, Hôpital européen Georges Pompidou, F-75015, Paris, France.
Université Paris Cité, AP-HP, Hôpital Européen Georges Pompidou, DMU Psychiatrie et Addictologie, Service de Psychiatrie de l'adulte, F-75015, Paris, France.
Eur J Hum Genet. 2022 Oct;30(10):1171-1177. doi: 10.1038/s41431-022-01157-z. Epub 2022 Aug 2.
Von Hippel-Lindau (VHL) disease is one of the most common cancer predisposition syndromes. Penetrance is high with around 20% of children presenting detectable and curable manifestations of the disease at 15 years old. VHL predictive genetic testing (PGT) is recommended during childhood from age 5 years in France. Insufficient compliance to surveillance of VHL pathogenic variant (PV) carriers is associated with severe outcome. PGT experienced by children and their parents is probably critical in influencing future acceptance of the result and adherence to surveillance. We conducted a retrospective study on minors tested (aged 5 to 16 years old) from 2010 to 2020, in a multidisciplinary oncogenetics consultation which follows a 3-step protocol based on psychological familial support. The objectives were to assess the adherence to follow-up within the National Expert Center for inherited predispositions to renal tumors (PREDIR) network of VHL PV carriers and its benefit through tumor detection and medical interventions. A VHL PGT was carried out in 34 children. Among the 16 children diagnosed as VHL PV carriers addressed to the PREDIR network, none had discontinued surveillance after a median of 41 months. Follow-up examinations detected 11 tumors in 6 children, 4 have been surgically treated. All had a favorable outcome. Our data suggest that a specific and adapted procedure for PGT in at-risk VHL children as well as a follow-up, organized within a specialized expert network, fosters a complete adherence to the surveillance protocol and thus lead to a favorable clinical outcome.
希佩尔-林道（VHL）病是最常见的癌症易感性综合征之一。大约 20%的儿童在 15 岁时就出现可检测到的、可治愈的疾病表现，其外显率很高。法国建议在儿童时期（5 岁起）进行 VHL 预测性基因检测（PGT）。VHL 致病性变异（PV）携带者的监测依从性不足与严重后果有关。儿童及其父母的 PGT 经验可能对未来对结果的接受程度和对监测的依从性产生重要影响。我们对 2010 年至 2020 年期间在多学科肿瘤遗传学咨询中心进行的未成年人（5 至 16 岁）检测进行了回顾性研究，该咨询中心遵循基于心理家庭支持的 3 步方案。目的是评估在 VHL PV 携带者的国家遗传性肾肿瘤倾向专家中心（PREDIR）网络中进行监测的依从性，以及通过肿瘤检测和医疗干预来提高其获益。对 34 名儿童进行了 VHL PGT。在被转介到 PREDIR 网络的 16 名被诊断为 VHL PV 携带者的儿童中，无一人在中位数为 41 个月后停止监测。随访检查在 6 名儿童中发现了 11 个肿瘤，其中 4 个已接受手术治疗。所有患儿均获得良好结局。我们的数据表明，为高危 VHL 儿童进行 PGT 以及在专门的专家网络内进行监测，制定特定的、适配的程序，可促进对监测方案的完全依从性，从而带来有利的临床结局。
