The utility of detailed first trimester ultrasound examination in abnormal fetal nuchal translucency.

OBJECTIVE: To determine the value of a first trimester fetal ultrasound examination in cases of an increased nuchal translucency (NT). METHOD: A detailed fetal ultrasound examination was performed within 4 days of a detection of a first trimester increased NT. RESULTS: As many as 23 fetuses were evaluated. Severe anomalies were detected in eight and mild anomalies were detected in six fetuses. Two fetuses had trisomy 13, one had trisomy 21, and 16 fetuses had a normal karyotype. A chromosomal analysis was not available in four fetuses with major anomalies due to parental decision. In one fetus, craniosynostosis was detected only at 24 weeks' gestation. CONCLUSIONS: The current study shows that a first trimester targeted scan of fetuses with an increased NT in an experienced center can shorten the parental decision-making process and spare parents a prolonged period of diagnostic uncertainty and anxiety, particularly when a structural anomaly is clearly diagnosed in the first trimester.

AgNOR increase in buccal epithelial cells of trisomy 21 infants.

The aim of this study is to compare the Argilophilic Nucleolus Organizer Regions (AgNORs) level between Down syndrome (DS) patients and controls in a tissue sharing the same embryonic origin with the central nervous system and compare the results with those obtained recently by us from DS's lymphocytes. For this, buccal desquamating epithelial cells well known as the ectodermic origin were used. Since the AgNOR staining intensity is an indicator of the ribosomes biosynthesis rate, comparison of the image analysis values of the AgNOR area/total nuclear area (NORa/TNa) in buccal desquamating epithelial cells of DS patients and controls provided a plausible conclusion about the regulation/deregulation of the rRNA genes (rDNA) in these cells of DS babies/infants. The (NORa/TNa) proportion was calculated using an in-house computer program. Fifty buccal desquamating cells were analysed for each individual to determine the average NORa/TNa value per individual. In contrast to healthy controls, NORa/TNa proportion value of buccal epithelial cells from DS patients found significantly higher than that of the controls: (4.08+/-1.16)% and (2.13+/-0.55)%, respectively. This 92% increase is far higher than the expected value due to the extra rRNA genes on the extra-chromosome 21. Finally DS babies/infants exhibit very higher AgNOR expression increase in their buccal epithelial cells compared to controls. This is the first study that is available on the comparison of AgNOR expression levels in buccal epithelial cells between DS infants and their controls.

Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome.

Neurodegeneration in fetal development of Down syndrome (DS) patients is proposed to result in apparent neuropathological abnormalities and to contribute to the phenotypic characteristics of mental retardation and premature development of Alzheimer disease. In order to identify the aberrant and specific genes involved in the early differentiation of DS neurons, we have utilized an in vitro neuronal differentiation system of mouse ES cells containing a single human chromosome 21 (TT2F/hChr21) with TT2F parental ES cells as a control. The paired protein extracts from TT2F and TT2F/hChr21 cells at several stages of neuronal differentiation were subjected to two-dimensional polyacrylamide gel electrophoresis protein separation followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to identify the proteins differentially expressed between TT2F and TT2F/hChr21 cells. We provide here a novel set of specific gene products altered in early differentiating DS neuronal cells, which differs from that identified in adult or fetal brain with DS. The aberrant protein expression in early differentiating neurons, due to the hChr21 gene dosage effects or chromosomal imbalance, may affect neuronal outgrowth, proliferation and differentiation, producing developmental abnormalities in neural patterning, which eventually leads to formation of a suboptimal functioning neuronal network in DS.

Deficits of neuronal density in CA1 and synaptic density in the dentate gyrus, CA3 and CA1, in a mouse model of Down syndrome.

Ts65Dn mice are partially trisomic for the distal region of MMU16, which is homologous with the obligate segment of HSA21 triplicated in Down syndrome (DS). Ts65Dn mice are impaired in learning tasks that require an intact hippocampus. In order to investigate the neural basis of these deficits in this mouse model of Down syndrome, quantitative light and electron microscopy were used to compare the volume densities of neurons and synapses in the hippocampus of adult Ts65Dn (n=4) and diploid mice (n=4). Neuron density was significantly lower in the CA1 of Ts65Dn compared to diploid mice (p<0.01). Total synapse density was significantly lower in the dentate gyrus (DG; p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. The synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. When the data were broken down by synapse type, asymmetric synapse density was found to be significantly lower in the DG (p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, while such a difference in symmetric synapse density was only present in the DG (p<0.01). The asymmetric synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, but there were no such significant differences in symmetric synapse-to-neuron ratios. These results suggest that impaired synaptic connectivity in the hippocampus of Ts65Dn mice underlies, at least in part, their cognitive impairment.

Nuclear volume and total optical density in Down syndrome.

OBJECTIVE: To estimate nuclear size and integrated optical density of parenchymal cells from various organs in patients with Down syndrome and a control group. STUDY DESIGN: During the years 1988-2000, 14 cases of Down syndrome were found (8 male and 6 female). Ten infants without congenital anomalies died of respiratory distress syndrome and were used as a control group. Five nuclear variables were estimated: area, equivalent diameter, volume of equivalent sphere, roundness and total optical density (TOD). RESULTS: Mean nuclear volume and TOD of thyroid follicular cells were significantly lower in patients with Down syndrome (43.82 +/- 8.95 and 173.81 +/- 32.85 microns 3, respectively) than in the control group (65.46 +/- 15.31 and 234.58 +/- 32.85 microns 3, respectively) (P < .01). Mean hepatocite nuclear volume and TOD were significantly higher in the control group (165.54 +/- 55.42 and 220.84 +/- 51.75 microns 3, respectively) than in trisomy 21 (110.39 +/- 32.97 and 176.58 +/- 28.53 microns 3, respectively) (P < .05). CONCLUSION: The present results suggest altered gene expression in excessive genetic material, especially in thyroid follicular cells.

Mothers' knowledge of screening for trisomy 21 in 1999: a survey in Paris maternity units.

OBJECTIVE: To assess mothers' knowledge of screening tests for trisomy 21. STUDY DESIGN: Interview of all women who had recently delivered a healthy child and were present in 15 Paris maternity units during one of the two non-consecutive days in June 1999 (N = 734). RESULTS: Two-third said that they had access to a nuchal translucency measurement (NTM) and to maternal serum screening (MSS), and 16% to amniocentesis. Thirty-eight percent of the women who had NTMs and 69% of those who had serum screening said that they had been informed of the need for amniocentesis if the results were abnormal. Among the women who had amniocentesis, 20% did not know the risk of miscarriage and 41% had not been informed about the possibility of terminating the pregnancy if trisomy 21 was diagnosed. CONCLUSIONS: Mothers' knowledge about the screening tests for trisomy 21 remains fragmentary. Providing comprehensive information about all these tests should be considered in early pregnancy so that women can make informed choices.