CASE SERIES Case 1A 30-year-old woman was referred at 13 + 1 weeks' gestation for first-trimester screening. The fetus had a crown-rump length (CRL) of 72 mm and a nuchal Figure 1 The mid-sagittal view is the best plane for evaluating intracranial translucency (IT) and the posterior brain region. This ultrasound image in a 13-week fetus illustrates the landmarks typical of a normal examination. The thalamus (Th) and brainstem (BS) have a hypoechoic appearance. The fourth ventricle, also called the IT, appears as an anechoic region with two horizontal echogenic borders, allowing reliable identification: the anterior border of the IT is the posterior border of the BS, and the posterior border of the IT is the choroid plexus (Chor. plex.) of the fourth ventricle. The choroid plexus is a well-recognized structure floating in the fluid of the IT and the future cisterna magna (f.CM), which are still connected to one another. The brainstem-occipital bone distance (BSOB) appears larger than does the brainstem diameter itself. OB, occipital bone. translucency thickness (NT) of 1.7 mm. Routine examination of the posterior brain failed to show the expected normal anatomy (Figure 1) 1,2 ; instead the brainstem appeared thickened and shifted backward toward the occipital bone (Figure 2), such that the ratio of brainstem diameter to brainstem-occipital bone distance (BS/BSOB ratio) was increased 3 , with a value of 1

Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effect due to the trisomic chromosome a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to obtain more insights into the molecular etiopathology of aneuploidy. Using oligonucleotide microarrays, we analyzed whole genome expression profiles in cultured amniocytes (AC) and chorionic villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 13, 18 and 21. We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional levels of most of the genes on the supernumerary chromosome appeared similar to the respective chromosomal pair in normal karyotypes. A subset of chromosome 21 genes including the DSCR1 gene involved in fetal heart development was consistently up-regulated in different prenatal tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 18 vigorous downstream transcriptional changes were found. Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses.

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