Prenatal diagnosis of an isochromosome 5p in a fetus with increased nuchal translucency thickness and pulmonary atresia with hypoplastic right heart at 14 weeks

We report on a fetus presenting with increased nuchal translucency at 11 weeks' gestation, suggesting cystic hygroma. Chorion villous sampling was performed, and cytogenetic analysis revealed a supernumerary isochromosome 5p leading to tetrasomy 5p: 47,XX,+ i(5p)[7]/46,XX[5] after short-term culture and 47,XX,+ i(5p)[20] after long-term culture. Subsequent targeted sonographic follow-up at 12 and 14 weeks revealed further increase of the NT to 6.4 mm and the additional presence of a congenital heart defect (pulmonary atresia with intact ventricular septum). Termination of pregnancy was performed, and the heart defect was confirmed. Isochromosome 5p was found in varying proportions in all examined organs. Only a few cases of mosaic tetrasomy 5p have been reported in the literature, and recent reports on prenatally detected isochromosome 5p showed a possible relationship to increased nuchal translucency in some cases and also a possible role of confined mosaicism in others. Whereas cases with confined mosaicism did not show suspicious signs on ultrasound, true mosaicism conversely showed increased nuchal thickness as well as structural abnormalities. This is the first report on the association of a cardiac defect with this chromosome aberration. Copyright © 2004 John Wiley & Sons, Ltd.     

Prenatal findings in a monozygotic twin pregnancy with Costello syndrome

This report describes the prenatal findings in monozygotic twins with Costello syndrome. At 16 weeks one twin had 9 mm of nuchal oedema: coarctation of the aorta was diagnosed after birth. At 22^5/7 weeks relative macrocephaly, mild pyelectasia and moderate polyhydramnios were noted in both twins. In the following 4 weeks the polyhydramnios increased significantly without visualisation of filling of the stomach. Between 27^5/7 and 30^2/7 weeks a total of 9 l amniotic fluid was drained and at 30^4/7 weeks prelabor premature rupture of membranes (PPROM) occurred followed by premature labor and delivery. The neonatal period was complicated by growth retardation, deglutition problems, hypotonia, cardiac and respiratory problems. Both twins died on Day 57 because of respiratory insufficiency. Copyright © 2002 John Wiley & Sons, Ltd.     

Minute chromatin structures in cells of amniotic fluid—an interpretative dilemma

Single copies of tiny chromosome fragments, appearing either as single or as double minutes, were observed in a high frequency in amniotic fluid cultures of five mothers who underwent prenatal testing because of advanced age. In four cases, the minutes had arisen de novo. The minutes were later confirmed in fetal skin following termination of pregnancy in one case; in another, in cord blood following the birth of a normal boy; and in the third, in peripheral blood of a normal 3-year-old girl. In the fourth case, the minutes were not confirmed in cord blood following the birth of a normal boy. A follow-up chromosome study of the baby boy in the fifth case was not possible but the minutes were maternally transmitted.     

An increase in cost-effectiveness of first trimester maternal screening programmes for fetal chromosome anomalies is obtained by contingent testing

We assessed the discriminatory efficiency and cost-effectiveness of a novel way of organising first trimester screening for Down syndrome (DS), contingent testing, where a serological test (PAPP-A and β-hCG: the double test) is made in early first trimester and followed by nuchal translucency testing (NT) only in women with an intermediate risk, e.g. <1:65 and >1:1000, and not in all women as in normal first trimester screening (NFTS). Using Monte Carlo simulation contingent testing had a detection rate (DR) of 78.9% and a false-positive rate (FPR) of 4.0% for DS with 19.4% of women offered NT testing. The DR of NFTS was 85.5% and the FPR 4.4%. The decrease in NT screening was associated with an increase from 23% to 29% in the proportion of DS cases born. The cost of the contingent testing programme was £53 000 per DS case not born and £91 000 in NFTS. The number of aborted fetuses per DS case were 0.35 and 0.36, respectively. Thus, contingent testing is an organisation of first trimester screening where costs can be reduced with a marginal decrease in performance. Contingent testing is attractive in areas where NT screening is the bottleneck preventing the introduction of first trimester screening. Copyright © 2002 John Wiley & Sons, Ltd.