Prenatal diagnosis of partial monosomy 18p(18p11.2→pter) and trisomy 21q(21q22.3→qter) with alobar holoprosencephaly and premaxillary agenesis

A prenatal diagnosis of partial monosomy 18p(18p11.2→pter) and trisomy 21q(21q22.3→qter) in a fetus with alobar holoprosencephaly (HPE) and premaxillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counselling at 21 weeks' gestation due to sonographic findings of craniofacial abnormalities. Level II ultrasonograms manifested alobar HPE and median orofacial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FISH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der(18)t(18;21)(p11.2;q22.3), resulting from a maternal t(18;21) reciprocal translocation. The breakpoints were ascertained by molecular genetic analysis. The pregnancy was terminated. Autopsy showed alobar HPE with PMA, pituitary dysplasia, clinodactyly and classical 18p deletion phenotype but without the presence of major typical phenotypic features of Down syndrome. The phenotype of this antenatally diagnosed case is compared with those observed in six previously reported cases with monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 outside Down syndrome critical region. The present study shows that cytogenetic analyses are important in detecting chromosomal aberrations in pregnancies with prenatally detected craniofacial abnormalities, and adjunctive molecular investigations are useful in elucidating the genetic pathogenesis of dysmorphism. Copyright © 2001 John Wiley & Sons, Ltd.     

Increased fetal nuchal fold leading to prenatal diagnosis of ring chromosome 15

We report on the prenatal diagnosis of ring chromosome 15 in a fetus with increased nuchal fold and intrauterine growth restriction (IUGR). A 27-year-old woman gravida 2, para 1 had normal maternal serum screen tests in the early second trimester of the index pregnancy. Fetal nuchal fold thickening up to 8 mm was incidentally found during the routine obstetric ultrasound scan at 20 weeks' gestation. Amniocentesis was undertaken and the fetal karyotype was found to be 46,XY,r(15) on cytogenetic study. Fluorescence in situ hybridization (FISH) using a telomeric probe of chromosome 15 demonstrated a terminal deletion on the q arm of the ring-shaped chromosome 15. This is the first report of a prenatally diagnosed case of ring chromosome 15. Moreover, nuchal fold thickness in the second trimester may have a role in its prenatal diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal phenotype of Prader–Willi syndrome due to maternal disomy for chromosome 15

Prader–Willi syndrome (PWS) results from either paternal deletion of 15q11–q13, or maternal uniparental disomy (UPD) of chromosome 15 or imprinting center mutation. Prenatal diagnosis of PWS is currently indicated for chromosomal parental translocation involving chromosome 15 and for decreased fetal movements during the third trimester of gestation. Here we present the prenatal diagnosis of PWS during the first trimester of gestation and autopsy findings. Chorionic villus sampling (CVS) was performed for advanced maternal age at 13 weeks' gestation. CVS showed mosaicism including cells with a normal karyotype and cells with trisomy 15. Amniocentesis showed cells with a normal karyotype. Molecular analysis demonstrated that the fetus had a typical PWS abnormal methylation profile and maternal disomy for chromosome 15. Fetal ultrasound examination showed slightly enlarged lateral ventricles and hypoplasic male external genitalia without intra-uterine growth retardation. The autopsy showed a eutrophic male fetus with facial dysmorphy, hypoplasic genitalia, abnormal position of both feet and posterior hypoplasia of the corpus callosum. This report points out that in a karyotypically normal fetus with ambiguous male external genitalia and cerebral anomalies, extensive cytogenetic and molecular biology studies are strongly recommended because of risk of PWS. Copyright © 2003 John Wiley & Sons, Ltd.     

Prenatal investigation of a 45,X/46,X,r(?) karyotype in amniocytes using fluorescence in situ hybridization with an X-centromeric probe

The karyotype of cultured amniotic fluid cells obtained on the indication of advanced maternal age was shown to be a mosaic 45,X/46,X,r(?). The small size and banding pattern made it difficult to determine whether the ring was derived from and X or a Y chromosome, or even from an autosome. By using an X-centromeric probe and fluorescence in situ hybridization (FISH), we demonstrated the ring to have an X centromere. Thus, a more complete genetic counselling was possible. This confirms the usefulness of FISH in identifying and characterizing this and other chromosome rearrangements in prenatal diagnosis.     

An accessory marker derived from chromosome 20 and its co-existence with a mosaic trisomy 20 cell line

We report a 16-month-old boy with delayed psychomotor development, dysmorphic features, and failure to thrive. He had a mosaic karyotype detected prenatally: mos 46,XY/47,XY,+r(20)/47,XY,+20. After birth, the abnormal cell lines were confirmed in a number of tissues. The small ring chromosome was identified using fluorescence in situ hybridization as derived from chromosome 20. We compared our patient with previously reported cases of mosaic trisomy 20 detected prenatally and associated with an abnormal phenotype. In an attempt to characterize an r(20) syndrome, we also compared our case with two similar reports in the literature.     

Transboundary air pollution balance in the new integrated European environment

Ten out of the 12 new EU members, used to belong to the so-called “former eastern block”, with a post WWII environmental policy radically different from the tendencies followed in Western Europe. The lack of conservation regulations has resulted in a rather harmful industrialization, regarding natural resources and environmental quality. While air pollution transfer is a phenomenon of transboundary level, there is a particular interest in examining the contribution of the new EU member states to the environmental pressure faced by the older member states and vice versa. The current study utilises the official data for almost 20 years published by the European Monitoring and Evaluation Program concerning the transboundary transfer of NO_x and SO₂ in order to analyse the situation and discuss the present and future environmental policy regarding air pollution.