CRIFM Clinical Research Institute of Fetal Medicine PMC, 7-3-7, Uehommachi, Tennoji, Osaka #543-0001, Japan.
Semin Fetal Neonatal Med. 2012 Dec;17(6):353-9. doi: 10.1016/j.siny.2012.07.005. Epub 2012 Aug 22.
Fetal imaging technology has been advancing remarkably and prenatal detection and diagnoses have been moved forward from the second and third trimesters to the first trimester. Structural abnormalities detected by fetal imaging often lead to prenatal diagnoses of genetic disorders. However, there are still dilemmas in fetal diagnoses in normal karyotype cases with strong suspicion of congenital genetic disorders from sonographic findings. When fetal sonography reveals multiple minor abnormalities originating from various organs, counseling dilemmas and parental anxieties become greater than before karyotyping. Array-comparative genomic hybridization (aCGH) was developed as a high-resolution analysis of DNA copy number variations (CNVs). In seven cases presenting with abnormal brain structures by fetal imaging, abnormal CNVs were confirmed by aCGH but conventional karyotyping yielded normal results. Although careful patient selection is required in order to deal with microarray results and parental counseling, 'sonogenetics' - incorporating the idea of 'fetuses first' - will play an important role in the era of molecular genetics. Recent advances in non-invasive prenatal testing by using fetal cell-free DNA in maternal plasma has the potential to generate misleading prenatal diagnoses without the observation of fetuses. However, no fetal diagnoses should be made without observing fetuses and we must not forget 'the fetus as a patient'.
胎儿影像学技术取得了显著进展，产前检测和诊断已经从第二和第三孕期提前到第一孕期。胎儿影像学检测到的结构异常常常导致遗传疾病的产前诊断。然而，在超声检查强烈提示先天性遗传疾病而核型正常的情况下，胎儿诊断仍然存在困境。当胎儿超声检查显示源自不同器官的多种轻微异常时，与核型分析前相比，咨询困境和父母的焦虑感会更大。比较基因组杂交（array-comparative genomic hybridization，aCGH）是一种对 DNA 拷贝数变异（copy number variations，CNVs）进行高分辨率分析的技术。在 7 例因胎儿影像学检查发现异常脑结构而进行的检查中，aCGH 证实存在异常 CNVs，但常规核型分析结果正常。尽管需要仔细选择患者以处理微阵列结果和父母咨询，但“sonogenetics”——即“胎儿优先”的理念——将在分子遗传学时代发挥重要作用。最近，利用母体血浆中的胎儿游离 DNA 进行的非侵入性产前检测取得了进展，但如果不观察胎儿，可能会产生误导性的产前诊断。然而，如果不观察胎儿，就不应该进行任何胎儿诊断，我们绝不能忘记“胎儿也是患者”。
