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Minors at risk of von Hippel-Lindau disease: 10 years’ experience of predictive genetic testing and follow-up adherence


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.

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Fig. 1: Tree-step protocol.
Fig. 2: Patient's course.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


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This work was supported in part by INCa and the Association VHL-France. We thank Anne-Marie Birot and Matthieu Bruzzi for their contribution to the childcare circuit.


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RV, KLL, MS, VK, TB, LA, NB, CA, SR, APGR: conceived and designed the work that led to the submission, acquired data and played an important role in interpreting the results. Drafted or revised the manuscript. Approved the final version. Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Anne-Paule Gimenez-Roqueplo.

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The authors declare no competing interests.

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The research was approved by the AP-HP Centre Ethics Committee (IRB registration: #00011928; Reference:2021-10-03).

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Vibert, R., Lahlou-Laforêt, K., Samadi, M. et al. Minors at risk of von Hippel-Lindau disease: 10 years’ experience of predictive genetic testing and follow-up adherence. Eur J Hum Genet (2022).

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