Obstetrics and Gynecology Resident.
Gynecologic Oncology Fellow, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Duke University Health System, Durham, NC.
Obstet Gynecol Surv. 2024 Sep;79(9):539-546. doi: 10.1097/OGX.0000000000001297.
With advances in prenatal cell-free DNA (cfDNA) technology, the information available with cfDNA continues to expand beyond the common fetal aneuploidies such as trisomies 21, 18, and 13. Due to the admixture of maternal and fetal/placental DNA, prenatal cfDNA remains a screening test with the possibility of false-positive and false-negative results.
This review aims to summarize unusual incidental maternal and fetal genomic abnormalities detectable by cfDNA and to provide anticipatory guidance regarding management.
Of 140 articles identified with keywords such as "incidental" and "discordant" cfDNA, 55 original research articles, review articles, case series, and societal guidelines were reviewed.
Prenatal cfDNA may incidentally identify a spectrum of maternal genomic abnormalities such as malignancy, mosaicism, and copy number variants. When discordant with fetal diagnosis, these cases require additional investigation with maternal genetic testing and follow-up evaluation. Such incidental fetal/placental abnormalities may include rare autosomal trisomies, uniparental disomy, and triploidy. Further evaluation of fetal/placental abnormalities can be pursued with a combination of ultrasound and prenatal diagnosis with chorionic villous sampling and/or amniocentesis. Societal guidelines do not currently recommend cfDNA screening for rare autosomal trisomies, microdeletions, or copy number variants, and some experts suggest that sex chromosome screening should be opted in after counseling.
Knowledge about possible incidental findings with prenatal cfDNA is needed to inform pretest and posttest counseling with appropriate follow-up evaluation.
As cfDNA technology has advanced to include genome-wide findings, it is important for clinicians, genetic counselors, and societal guidelines to acknowledge the spectrum of possible results outside of the traditional and sex chromosome aneuploidies.
随着产前游离胎儿 DNA（cfDNA）技术的进步，cfDNA 提供的信息不断扩展，超出了常见的胎儿非整倍体，如 21、18 和 13 三体。由于母体和胎儿/胎盘 DNA 的混合，产前 cfDNA 仍然是一种筛查试验，存在假阳性和假阴性结果的可能性。
本综述旨在总结 cfDNA 可检测到的不常见偶然母体和胎儿基因组异常，并提供管理方面的预期指导。
使用“偶然”和“不一致”cfDNA 等关键词共确定了 140 篇文章，对其中 55 篇原始研究文章、综述文章、病例系列和社会指南进行了回顾。
产前 cfDNA 可能偶然发现母体基因组异常，如恶性肿瘤、嵌合体和拷贝数变异。当与胎儿诊断不一致时，这些病例需要进行额外的母体遗传检测和随访评估。这种偶然的胎儿/胎盘异常可能包括罕见的常染色体三体、单亲二体和三倍体。可以结合超声和产前诊断，使用绒毛膜绒毛取样和/或羊膜穿刺术进一步评估胎儿/胎盘异常。社会指南目前不建议对罕见常染色体三体、微缺失或拷贝数变异进行 cfDNA 筛查，一些专家建议在咨询后选择进行性染色体筛查。
需要了解产前 cfDNA 检测可能存在的偶然发现，以便为检测前和检测后咨询提供信息，并进行适当的随访评估。
随着 cfDNA 技术的进步，包括全基因组检测，临床医生、遗传咨询师和社会指南有必要承认传统和性染色体非整倍体以外的可能结果范围。
