RT Journal Article
SR Electronic
T1 Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmedgenet-2021-108216
DO 10.1136/jmedgenet-2021-108216
A1 Kenan Zhang
A1 Jianhui Qiu
A1 Wuping Yang
A1 Kaifang Ma
A1 Lei Li
A1 Haibiao Xie
A1 Yawei Xu
A1 Yanqing Gong
A1 Jingcheng Zhou
A1 Lin Cai
A1 Kan Gong
YR 2021
UL http://jmg.bmj.com/content/early/2021/12/16/jmedgenet-2021-108216.abstract
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.