Duffy Kelly A, Deardorff Matthew A, Kalish Jennifer M
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Am J Med Genet A. 2017 Mar;173(3):581-584. doi: 10.1002/ajmg.a.38068. Epub 2017 Feb 4.
Beckwith-Wiedemann syndrome (BWS) is one of the most common cancer predisposition disorders. As a result, BWS patients receive tumor screening as part of their clinical management. Until recently, this screening has been employed uniformly across all genetic and epigenetic causes of BWS, including the utilization of ultrasonography to detect abdominal tumors and alpha-fetoprotein (AFP) to detect hepatoblastoma. The advancements in our understanding of the genetics and epigenetics leading to BWS has evolved over time, and has led to the development of genotype/phenotype correlations. As tumor risk appears to correlate with genetic and epigenetic causes of BWS, several groups have proposed alterations to tumor screening protocols based on the etiology of BWS, with the elimination of AFP as a screening measure and the elimination of all screening measures in BWS patients with loss of methylation at the KCNQ1OT1:TSS-DMR 2 (IC2). There are many challenges to this suggestion, as IC2 patients may have additional factors that contribute to risk of hepatoblastoma including fetal growth patterns, relationship with assisted reproductive technologies, and the regulation of the IC2 locus. © 2017 Wiley Periodicals, Inc.
贝克威思-维德曼综合征（BWS）是最常见的癌症易感疾病之一。因此，BWS患者在临床管理中需要接受肿瘤筛查。直到最近，这种筛查在所有导致BWS的遗传和表观遗传原因中都统一采用，包括利用超声检查来检测腹部肿瘤以及利用甲胎蛋白（AFP）来检测肝母细胞瘤。随着时间的推移，我们对导致BWS的遗传学和表观遗传学的理解不断进步，进而形成了基因型/表型相关性。由于肿瘤风险似乎与BWS的遗传和表观遗传原因相关，一些研究团队基于BWS的病因对肿瘤筛查方案提出了调整建议，包括取消AFP作为筛查手段，以及取消KCNQ1OT1:TSS-DMR 2（IC2）甲基化缺失的BWS患者的所有筛查措施。这一建议面临诸多挑战，因为IC2患者可能还有其他导致肝母细胞瘤风险增加的因素，包括胎儿生长模式、与辅助生殖技术的关系以及IC2基因座的调控。© 2017威利期刊公司
