First-trimester diagnosis of Bartsocas–Papas syndrome (BPS) by transvaginal ultrasound: case report and review of the literature

Initially described in 1972, Bartsocas–Papas syndrome (BPS) is an autosomal recessively inherited disorder combining multiple pterygia, ankyloblepharon, cleft lip and palate, filiform bands between the jaws, syndactyly, and other anomalies. Although described as lethal, review of the literature reveals three individuals who survived into childhood with this condition. We describe a fourth surviving patient and what we believe to be the first prenatal diagnosis of BPS in the first trimester. Copyright © 2003 John Wiley & Sons, Ltd.     

Prenatal diagnosis of sacrococcygeal teratoma with constitutional partial monosomy 7q/trisomy 2p

We report the prenatal diagnosis of a fetus with sacrococcygeal teratoma and facial dysmorphism attributed to a constitutional terminal deletion of chromosome 7q and partial trisomy of chromosome 2p likely resulting from a de novo balanced translocation. The cytogenetic abnormality was diagnosed prenatally after sonographic detection of teratoma and confirmed on peripheral blood cells at birth. The newborn died of post-operative complications at seven days of age. FISH analysis demonstrated haploinsufficiency of HLXB9, a gene identified in the triad of a presacral mass (teratoma or anterior meningocele), sacral agenesis, and anorectal malformation, which constitutes the Currarino syndrome. Despite the absence of other features of the triad, the teratoma observed in the fetus we describe might represent a partial form of Currarino syndrome. Copyright © 2003 John Wiley & Sons, Ltd.     

Fetal diaphragmatic hernia and upper limb anomalies suggest Brachmann-de Lange syndrome

We describe two independent cases of Brachmann-de Lange syndrome (BDLS) in which second trimester fetal sonographic studies showed the presence of a diaphragmatic hernia and upper limb anomalies. In both cases the karyotypes were normal. Intrauterine growth restriction (IUGR) developed in the third trimester. Postnatal and postmortem physical examinations demonstrated typical physical findings associated with BDLS. The prenatal diagnosis of diaphragmatic hernia with associated anomalies should prompt consideration of an underlying genetic etiology. Copyright © 2002 John Wiley & Sons, Ltd.     

Low or absent unconjugated estriol in pregnancy: an indicator for steroid sulfatase deficiency detectable by fluorescence in situ hybridization and biochemical analysis

It has been previously reported that a low or absent maternal serum unconjugated estriol (uE3) level is associated with placental steroid sulfatase (STS) deficiency. Here we report a correlation between patients who present with a very low or absent maternal serum uE3 and a deletion of the STS gene as assessed by fluorescence in situ hybridization (FISH). We studied nine prenatal cases that presented to the clinical laboratory with an abnormal triple screen, specifically low or absent maternal serum uE3 and a 46,XY karyotype. FISH analysis showed complete deletion of a probe containing the STS gene in six cases and one case had a partial deletion (reduced but not absent signal). The remaining two cases were not deleted for the STS probe. All mothers tested whose fetus showed a deletion were shown to be STS deletion carriers using FISH. Biochemical analysis was performed on 7/9 prenatal specimens. All fetuses deleted for the STS probe were also found to be deficient for STS by biochemical analysis of cultured amniotic fluid (5/5). Of the two fetuses not deleted for the STS probe, one was deficient for STS activity, while the other had a normal result. The abnormal result of enzyme deficiency by biochemical analysis in a non-deletion case likely represents a mutation in the STS gene, not detectable by this FISH assay. Postnatal FISH confirmation of the STS deletion was performed in 1/7 cases. Clinical follow-up was available for 4/9 cases following birth. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of cri du chat (5p-) syndrome in association with isolated moderate bilateral ventriculomegaly

A case of prenatally detected cri du chat syndrome (5p-) is reported. Amniocentesis was performed following an abnormal ultrasound finding of isolated moderate bilateral ventriculomegaly. The karyotype showed a terminal deletion of the short arm of chromosome 5 including the critical region 5p15 for cri du chat syndrome. This was confirmed by fluorescence in situ hybridisation (FISH). Isolated mild ventriculomegaly may be a non-specific marker for cri du chat syndrome. Copyright © 2002 John Wiley & Sons, Ltd.     

Complete discrepancy between abnormal fetal karyotypes predicted by QF-PCR rapid testing and karyotyped cultured cells in a first-trimester CVS

A chorion villus sample (CVS) biopsied at 11 weeks' gestation for raised nuchal translucency, revealed monosomy X (presumptive 45,X karyotype) by QF-PCR for rapid aneuploidy testing for chromosomes 13, 18, 21, X and Y. Long-term culture gave the karyotype: 47,XY,+ 21[66]/49,XYY,+ 21,+ 21 [22]. This discrepancy prompted redigestion of the combined residual villus fragments from the original QF-PCR assay. The repeat QF-PCR assay identified the presence of trisomy 21 and a Y chromosome consistent with a 47,XY,+ 21 karyotype. A double non-disjunction event early in embryogenesis in a 47,XY,+ 21 conceptus with subsequent cell lineage compartmentalisation of the three observed cell lines (45,X; 47,XY,+ 21 and 49,XYY,+ 21,+ 21) would account for these results. This is the first reported case to describe complete discrepancy at diagnosis between abnormal karyotypes detected by QF-PCR rapid aneuploidy testing and a cultured karyotype in the same CVS. Copyright © 2006 John Wiley & Sons, Ltd.     

Does a ‘notched’ nuchal translucency indicate Down syndrome fetuses or other adverse pregnancy outcome?

The aim of the present study was to assess the sonographic contour of the increased nuchal translucency (NT) and to correlate this with pregnancy outcome. Fifty sonographic images of fetuses with increased NT [>95th centile thickness of the normal range for crown–rump length (CRL) between 38 and 84 mm] were retrospectively assessed. In all the cases a complete pregnancy and even infancy follow-up (<36 months) was available. The NT appearances were subdivided into two forms: a ‘notched’ or ‘uniform’ appearance. The images were correlated with karyotype results [trisomy 21 (DS) vs euploid cases] and pregnancy outcome. Complicated outcomes were classified as being either DS fetuses, miscarriage or termination of pregnancy because of structural anomaly. Thus 30/35 (86%) of the euploid fetuses had a ‘uniformly’ increased NT, whereas 8/13 DS cases (62%) had a ‘notched’ appearance (Fisher's exact test, p=0.004). Additionally, 27/29 fetuses (93%) which had an uneventful pregnancy outcome had a ‘uniform’ increased NT, whereas 12/26 (57%) of the fetuses which had adverse pregnancy outcome had a ‘notched’ appearance of their NT (Fisher's exact test, p<0.001). Although it was not possible to correlate the sonographic data with post-evacuation microdissection findings, it is possible that a uniformly shaped, increased NT may be more representative of a developmental delay in a normal fetus. Conversely, a ‘notched’ nuchal surface may represent abnormal lymphatic or cardiovascular development more commonly seen in DS fetuses. Copyright © 2001 John Wiley & Sons, Ltd.