Cohen Jennifer L, Duyzend Michael, Adelson Sophia M, Yeo Julie, Fleming Mark, Ganetzky Rebecca, Hale Rebecca, Mitchell Deborah M, Morton Sarah U, Reimers Rebecca, Roberts Amy, Strong Alanna, Tan Weizhen, Thiagarajah Jay R, Walker Melissa A, Green Robert C, Gold Nina B
Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA.
Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Am J Hum Genet. 2025 Jun 5;112(6):1251-1269. doi: 10.1016/j.ajhg.2025.03.011. Epub 2025 Apr 9.
The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade. Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS. In the United States, GS for adults and children is recommended to include a list of "secondary findings" genes (ACMG SF v.3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v.3.2 predominantly cause adult-onset disorders. Importantly, many genetic disorders with fetal and infantile onset are treatable as well. A proposed solution is to create a "treatable fetal findings list," which can be offered to pregnant individuals undergoing fetal GS or, eventually, as a standalone cell-free fetal DNA screening test. In this integrative review, we propose criteria for a treatable fetal findings list, then identify genetic disorders with clinically available or emerging fetal interventions and those for which clinical detection and intervention in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of a treatable fetal findings list.
在过去十年中，基因组测序（GS）用于产前诊断超声异常胎儿的应用有了巨大增长。胎儿GS还提供了一个机会，来识别与胎儿表型无关但可能与胎儿和新生儿健康相关的偶然基因组变异。目前尚无关于报告胎儿GS偶然发现的指南。在美国，建议对成人和儿童进行的GS包括一份“次要发现”基因列表（ACMG SF v.3.2），这些基因与通过监测或治疗可降低发病率和死亡率的疾病相关。ACMG SF v.3.2上的基因主要导致成人发病的疾病。重要的是，许多胎儿期和婴儿期发病的遗传疾病也是可治疗的。一个提议的解决方案是创建一个“可治疗胎儿发现列表”，该列表可提供给接受胎儿GS的孕妇，或者最终作为一项独立的游离胎儿DNA筛查测试。在这篇综合综述中，我们提出了可治疗胎儿发现列表的标准，然后识别出有临床可用或正在出现的胎儿干预措施的遗传疾病，以及那些在出生后第一周进行临床检测和干预可能会改善结局的疾病。最后，我们综合了可治疗胎儿发现列表的潜在益处、局限性和风险。
