Rudd Ignatius, Gill Gulvir, Buckley Michael, Downie Lilian
Department of Perinatal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia.
Genetics in the North East, Mercy Hospital for Women, Melbourne, Victoria, Australia.
Am J Med Genet A. 2023 Dec;191(12):2856-2859. doi: 10.1002/ajmg.a.63372. Epub 2023 Aug 14.
The introduction of genomic testing into prenatal care has come at a rapid pace and has been met with significant clinical and ethical challenges, specifically when dealing with incidental findings. We present the case of a couple in their first pregnancy who were referred to our institution with isolated fetal cataracts on morphology scan. After an unremarkable infectious disease workup and microarray on an amniocentesis sample, the couple opted for fetal whole-exome sequencing to investigate the cataracts further. This investigation did not find any cause for the cataracts but yielded an incidental finding of a de novo pathogenic variant in the SCN1A gene unrelated to the cataracts. Pathogenic variants in the SCN1A gene are strongly associated with severe myoclonic epilepsy of infancy, or Dravet syndrome. After extensive genetic counseling, the couple decided to terminate the pregnancy at 28 weeks' gestation based on this finding. This case highlights some of the important clinical and ethical considerations in prenatal genetic diagnosis, particularly in the group of patients in which there is no phenotypic evidence in-utero of the incidental finding. The case demonstrates the value of frameworks and guidelines to guide management decisions for both clinicians and patients.
基因组检测引入产前护理的速度很快，并面临重大的临床和伦理挑战，尤其是在处理偶发发现时。我们介绍一对首次怀孕的夫妇的案例，他们因形态学扫描发现孤立性胎儿白内障而被转诊至我院。在对羊膜穿刺术样本进行了无异常的传染病检查和微阵列分析后，这对夫妇选择进行胎儿全外显子测序以进一步研究白内障。这项检查未发现白内障的任何病因，但偶然发现了SCN1A基因中的一个新生致病性变异，该变异与白内障无关。SCN1A基因中的致病性变异与婴儿严重肌阵挛性癫痫或德拉韦综合征密切相关。经过广泛的遗传咨询，这对夫妇基于这一发现决定在妊娠28周时终止妊娠。该案例凸显了产前基因诊断中一些重要的临床和伦理考量，特别是对于那些在子宫内没有偶发发现的表型证据的患者群体。该案例展示了指导临床医生和患者管理决策的框架和指南的价值。
