PT - JOURNAL ARTICLE AU - Kenan Zhang AU - Jianhui Qiu AU - Wuping Yang AU - Kaifang Ma AU - Lei Li AU - Haibiao Xie AU - Yawei Xu AU - Yanqing Gong AU - Jingcheng Zhou AU - Lin Cai AU - Kan Gong TI - Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients AID - 10.1136/jmedgenet-2021-108216 DP - 2021 Dec 13 TA - Journal of Medical Genetics PG - jmedgenet-2021-108216 4099 - http://jmg.bmj.com/content/early/2021/12/16/jmedgenet-2021-108216.short 4100 - http://jmg.bmj.com/content/early/2021/12/16/jmedgenet-2021-108216.full AB - Background Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors.Methods In this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis.Results The estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group.Conclusion This study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.Data are available upon reasonable request.