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Molecular findings in the proband. Chromosomal Microarray Analysis (CMA) data from the X chromosome with a normalized copy number state ~2 in PAR1 and PAR2, and ~1 across the remainder of the chromosome with a long contiguous stretch of homozygosity observed proximally, and regions of heterozygosity observed distally.
Source publication
Key Clinical Message
Low fraction fetal DNA in noninvasive prenatal testing in the context of fetal growth restriction and multiple congenital anomalies should alert medical professionals to the possibility of digynic triploidy. Single-nucleotide polymorphism microarray can detect the parental origin of triploidy and explain its mechanism.
Citations
... non-invasive prenatal testing (NIPT) has become a common screening test for chromosome abnormalities in early pregnancy. However, NIPT can identify only diandric triploidy rather than digynic triploidy due to low cell-free fetal DNA fraction [22,23]. Polymorphic marker analysis has the advantage of determination of parental origin in case of triploidy. ...
Objective
We present digynic triploidy in a fetus with semilobar holoprosencephaly (HPE).
Case report
A 32-year-old, gravid 1, para 0, woman underwent prenatal ultrasound examination at 12 weeks of gestation, and the ultrasound showed relative macrocephaly, a small non-cystic placenta, and a fetus with absent nasal bone and semilobar HPE. The pregnancy was terminated subsequently, and a 50-g fetus was delivered with a relatively enlarged head and premaxillary agenesis. The placenta was small and non-cystic. Postnatal cytogenetic analysis of the umbilical cord revealed a karyotype of 69, XXX. Postnatal DNA marker analysis using quantitative fluorescent polymerase chain reaction assays and the polymorphic short tandem repeat markers for chromosome 18 and 20 on the placental tissues showed a diallelic pattern with a dosage of 1:2 (paternal allele to maternal allele ratio), indicating a maternal origin of the triploidy.
Conclusion
Fetuses with digynic triploidy may present relative macrocephaly, semilobar HPE and a small placenta on prenatal ultrasound.
... However, in addition to fetal aneuploidy, foetal, placental, maternal or other abnormalities have been frequently detected using both prenatal invasive and non-invasive diagnosis [3,4]. Some abnormalities are technically difficult to detect by prenatal diagnosis or remain undetected [5], whereas other abnormalities are indicators of certain diseases [6]. The current study examined a case of confined placental trisomy 16 mosaicism with intrauterine growth retardation (IUGR), apparent thickening of the placenta, placental lake and oligoamnios. ...
... Invasive diagnostic methods, such as amniocentesis or CVS, have long been regarded as the gold standard for aneuploidy confirmation [7]. However, placental abnormality and severe oligohydramnios may lead to failed amniocentesis, and some reported cases associated with severe oligohydramnios render amniocentesis technically difficult or failed [5]. Stagnation of fetal development and abnormal metabolism for the fetus may result in a small quantity of fetal cells in the amniotic fluid. ...
... Background information on why a test does not provide a result is important as it may trigger a more targeted follow-up examination 3 . It was shown that cases with no result due to low FF carry an increased risk for trisomy 13, trisomy 18 and triploidy, but not for trisomy 21 (T21) [3][4][5] . This is in contrast with cases with no test result due to technical failure for which there is no evidence of an increased risk for aneuploidy. ...
As a postlude, this chapter addresses several rather specific and technical questions and concerns that are sometimes levelled against the definition and criteria of life and death developed in this book, especially the notion of the soul as the principle of life. This chapter is meant for those readers who are interested in a more in-depth discussion of theoretical aspects concerning ensoulment in general and ensoulment with a rational soul in particular.
The case of dichorionic twin pregnancy is described, with a fused placenta, one part of which is represented by a tissue of partial hydatidiform mole (PHM) with signs of regression, the second part is a placenta of a common structure with a normal development of the second twin. The delivery took place at the term of 38 weeks with a live healthy girl weighing 3250 g. A single placental disc consisted of two fused placentas with a clear boundary between them. The placenta of a live-born girl was mature, with focal chorangiosis, the second part of the disc was represented by the PHM tissue with avascular giant bizarre villi, some of them with central cisterns, with stromal fibrosis, low proliferative activity of the villous trophoblast and a significant narrowing of the intervillous space. A genetic study was carried out on the material of paraffin blocks from two parts of the placental disc containing the tissue of the villous chorion, and the blood of the parents. Comparative analysis of DNA isolated from the paraffin block of PHM with the DNA of the parents revealed the presence of diandric dispermic triploidy. No chromosomal pathology was found in the placenta of a living girl. For hydatidiform mole in the case of multiple pregnancy, an increase in the volume of the affected placenta is characteristic compared to the normal placenta of the twin. In our observation, the presence in the placenta with PHM signs characteristic of placentas with antenatal fetal death, stromal fibrosis of the villi and low proliferative activity of the trophoblast suggests a regression of PHM.
Cell-free fetal DNA analysis has an established role in prenatal assessments. It serves as a source of fetal genetic material that is accessible non-invasively from maternal blood. Through the years, evidence has accumulated to show that cell-free DNA molecules are derived from placental tissues, are mainly of short DNA fragments and have rapid post-delivery clearance profiles. But questions regarding how they come to being short molecules from placental cells and in which physical forms do they exist remained largely unanswered until recently. We now know that the distributions of ending sites of cell-free DNA molecules are non-random across the genome and bear correlations with the chromatin structures of cells from which they have originated. Such an insight offers ways to deduce the tissue-of-origin of these molecules. Besides, the physical nature and sequence characteristics of the ends of each cell-free DNA molecule provide tell-tale signs of how the DNA fragmentation processes are orchestrated by nuclease enzymes. These realizations offered opportunities to develop methods for enriching cell-free fetal DNA to facilitate non-invasive prenatal diagnostics. Here we aimed to collate what is known about the biological and physical characteristics of cell-free fetal DNA into one article and explain the implications of these observations. This article is protected by copyright. All rights reserved.
Background:
Placental pathology in fetal congenital anomalies in second half of pregnancy is largely unknown.
Methods:
Twenty-six clinical and 45 independent placental phenotypes from pregnancies ≥20 weeks of gestation with congenital anomalies divided into 4 groups were retrospectively compared with analysis of variance or χ 2 with 3 degrees of freedom and with Bonferroni correction for multiple comparisons: group 1 : 112 cases with heart malformations (with or without chromosomal anomalies), group 2 : 41 cases with abnormal karyotypes and anomalies other than heart malformations, group 3 : 87 cases with intrathoracic or intraabdominal mass-forming anomalies (mostly congenital diaphragmatic hernias and adenomatoid airway malformation), and group 4 : 291 miscellaneous cases with mostly skeletal, renal, and central nervous system anomalies not fulfilling the criteria of inclusion into groups 1 to 3.
Results:
Eight of 26 clinical (30.8%) and 16 of 45 (35.5%) placental phenotypes varied statistically significantly among the 4 groups ( P < .05), of those, 7 (26.9%) and 4 (8.9%), respectively, remained statistically significant after Bonferroni correction ( P Bonferroni ≤ .002). Those placental phenotypes were placental weight, chorionic disc chorionic microcysts, fetal vascular ectasia, and luminal vascular abnormalities of chorionic villi.
Conclusions:
Fetal anomalies in second half of pregnancy feature abnormal clinical phenotypes much more frequently than abnormal placental phenotypes. Chromosomal abnormalities with or without heart malformations tend to feature villous edema, and erythroblastosis of fetal blood, likely due to fetal heart failure. Mass-forming fetal anomalies feature placental histological lesions of shallow placental implantation, diffuse chronic hypoxic patterns of placental injury, and lesions of fetal vascular malperfusion, likely stasis-induced.
