Marker For Chromosomal Abnormalities Research Articles

Пренатальная диагностика врожденной дисфункции коры надпочечников

Enlarged nuchal translucency and nasal bone hypoplasia are considered as markers of chromosomal abnormalities and fetal malformations, although enlarged nuchal translucency can be detected in a healthy fetus and completely disappear by 14–15 weeks’ gestation and can also be observed when the karyotype is normal (in antenatal fetal death, congenital heart disease, miscarriage, preterm birth). The study of markers of chromosomal abnormalities is of practical interest in terms of accumulating information and gaining experience in using them for prenatal diagnosis. A case of accurate sex determination in the fetus with salt-wasting form of congenital adrenal hyperplasia and virilization of the external genitalia (Prader grade IV) at birth is presented. Highly effective prenatal screening including amniocentesis and karyotyping (46XX) at 13 weeks’ gestation ensured that pediatricians were prepared for timely prescription of gluco- and mineralocorticoid replacement therapy. This enabled to prevent the development of acute adrenal crisis and choose adequate management tactics, thereby providing normal puberty and potential fertility. Key words: congenital adrenal hyperplasia, prenatal screening, enlarged nuchal translucency

Изучение хромосомных аномалий у плодов с УЗ-маркерами и пороками развития

Микроделеционные и микродупликационные синдромы выявляются примерно у 8% плодов с врожденными пороками развития (ВПР), однако диагностика патогенных CNVs в пренатальном периоде в данный момент не регламентирована и зачастую основана на технических возможностях лаборатории. Представлены результаты исследования плодов, которые имели ВПР и/или маркеры хромосомной патологии, установленные по УЗИ, методом хромосомного микроматричного анализа (ХМА). В выборке (N=1048) у 10,3% плодов были обнаружены числовые аномалии хромосом и у 7,4% плодов были выявлены патогенные хромосомные аномалии, которые невозможно выявить при стандартном кариотипировани из-за их малого размера. Результаты нашего анализа согласуются с данными литературы, демонстрирующей большую эффективность SNP-микроматриц по сравнению с классическими цитогенетическими методами. Microdeletion and microduplication syndromes are detected in approximately 8% of fetuses with congenital malformations, however, the diagnosis of pathogenic CNVs in the prenatal period, at the moment, is unregulated and often based on the technical capabilities of the laboratory. The thesis presents the result of a study of fetuses that had congenital malformations and / or markers of chromosomal abnormalities, determined by ultrasound, by the method of chromosomal microarray analysis. Using chromosomal microarray analysis in our sample (N = 1048), numerical chromosome abnormalities were detected in 10.3% of the fetuses and pathogenic chromosome imbalance was revealed in 7.4% of the fetuses, which cannot be detected by standard karyotyping. The results of our analysis are consistent with the data of the scientific literature, which demonstrates the greater efficiency of using SNP microarrays in comparison with classical cytogenetic methods.

Real possibilities of prenatal diagnosis of translocation form Down’s syndrome

Objective: analyses of real possibilities of prenatal diagnosis of translocation form Down’s syndrome. Materials: 243 cases of Down's syndrome were diagnosed within 15 years, translocation variant of trisomy 21 was found in 5 cases (2 %). The article provides the analyses of the results of prenatal examination of the fetuses with the translocation form of Down's syndrome. Results: in all 5 cases abnormal biochemical screening and ultrasound markers of chromosomal abnormalities were recorded. Prenatal karyotyping was carried out in one observation. In 4 cases cytogenetic diagnosis was performed postnatally. The perinatal outcome is known in all the observations. Conclusion: Prenatal diagnosis of the translocation form of Down's syndrome is possible in most cases, provided that the screening time of the examination of pregnant women is met and the indications for an expert ultrasound evaluation of the fetus using the latest technology are broadened

Уровень экспрессии гена кальмодулина в кумулюсных клетках как маркер наличия хромосомных аномалий в эмбрионах в программах экстракорпорального оплодотворения

Уровень экспрессии гена кальмодулина в кумулюсных клетках как маркер наличия хромосомных аномалий в эмбрионах в программах экстракорпорального оплодотворения

Screening for Fetal Aneuploidies in 1st Trimester

ABSTRACT Effective screening of fetal aneuploidy started in the early 1960s, initially based on the age of the mother. Recent screening protocols based on various maternal serum factors and on new ultrasound techniques during the 1st and 2nd trimester offered to all pregnant women noninvasive prognostic methods for risk assessment of chromosomal abnormalities and performanceinvasive prenatal diagnostic methods only in high-risk cases. In this review, we discuss the ultrasound and biochemical markers of chromosomal abnormalities in the 1st trimester, the evaluation of free fetal deoxyribonucleic acid in the peripheral blood of pregnant women, and different antenatal screening protocols as known today. How to cite this article Athanasiadis AP, Zavlanos AI. Screening for Fetal Aneuploidies in 1st Trimester. Donald School J Ultrasound Obstet Gynecol 2016;10(2):147-153.

Single umbilical artery – marker for chromosomal abnormalities: report of two postnatal cases

Single umbilical artery – marker for chromosomal abnormalities: report of two postnatal cases

Ultrasound soft markers and fetal cardiac structural assessment at 11-14 weeks

To evaluate the detection rate of congenital heart defect (CHD) during the first trimester screening for chromosomal abnormalities, the role of ultrasound soft markers including increased nuchal translucency (NT), tricuspid regurgitation (TR) and abnormal ductus venosus (DV) flow in the screening for cardiac anomalies was also investigated. From January 2009 to January 2012, 4 673 fetuses were scanned at 11-14 weeks at Department of Fetal Medicine, the First Affiliated Hospital of Jinan University. The ultrasound findings and follow up outcomes were recorded, False-positive rate of different first-trimester ultrasound markers for the detection of CHD was calculated, sensitivity of the markers for all major CHD was calculated as well. There was a significant association between major CHD and first trimester ultrasound markers. (1) Overall findings:among the 4 673 fetuses, 31 fetuses were diagnosed CHD prenatally, 17, 12 and 2 of which were detected in the first, second and third trimester, respectively. In 22 of the 31 CHD cases, invasive procedure was performed, fetal karyotype was abnormal in 12 cases, including triosmy 21 (5 cases), trisomy 18 (2 cases), trisomy 13 (2 cases), Turner syndrome (2 cases) and pericentric inversion of chromosome 9 (1 cases). (2) NT measurement and prenatal detected CHD: in 4 673 cases, NT measurement between 95(th)-99(th) percentile were present in 206 (4.41%) , 5 cases were diagnosed CHD prenatally, in 4 of 5 cases were detected in first trimester; NT measurement <95(th) percentile were present in 4 430 (94.80%) , 16 cases were diagnosed CHD prenatally, in 5 of 16 cases were detected in first trimester; NT measurement>99(th) percentile (>3.5 mm) were present in 37 (0.79%, 37/4 673) , 10 cases were diagnosed CHD prenatally, in 8 of 10 cases were detected in first trimester. (3) TR and inverted a-wave at the DV and prenatal detected CHD: among 4 673 cases, TR or inverted a-wave at the DV were present in 51 (1.09%) , 98 (2.10%) respectively. TR was present in 8 of 31 CHD cases, inverted a-wave at the DV was present in 7 of 31 CHD cases. (4) Sensitivity of different first trimester ultrasound markers for detection of major CHD cases:in 31 CHD cases diagnosed prenatally, 23 cased were defined as major CHD. Sensitivity of at least one of the ultrasound markers, NT measurement between 95(th)-99(th) percentile, >99(th) percentile( >3.5 mm), TR or inverted a-wave at the DV for detection of major CHD cases was 74% (17/23), 22% (5/23), 39% (9/23), 35% (8/23), 30% (7/23) , respectively. (5) Specificity of different first trimester ultrasound markers for detection of CHD cases:specificity of NT measurement between 95(th)-99(th) percentile, >99(th) percentile (>3.5 mm), TR or inverted a-wave at the DV for detection of major CHD cases was 4.30% (201/4 673),0.58% (27/4 673),0.92% (43/4 673), 1.94% (91/4 673). Routine first trimester soft markers for chromosomal abnormalities screening combined with cardiac assessment can detect quite a number of major heart defects. Increased NT, TR and abnormal DV flow can be important indicators for echocardiography, which is favorable to early prenatal diagnosis of CHD.

Increased nuchal translucency with normal karyotype and anomaly scan: What next?

Over the years, it has become clear that increased nuchal translucency is a marker for chromosomal abnormalities, and it is also associated with a wide spectrum of structural anomalies, genetic syndromes, a higher risk of miscarriage, and intrauterine fetal death. These risks are all proportionally related to the degree of nuchal translucency enlargement. After the initial assessment of increased nuchal translucency, parents should be counselled by the fetal medicine specialist about the possible outcomes and the value of additional karyotyping and array comparative genomic hybridisation. A detailed late first-trimester and subsequent 20-week scan should aim at identifying structural anomalies, with special focus on the fetal heart and subtle dysmorphic features. In the absence of structural anomalies or markers, the chance of a favourable outcome is high.

Aberrant right subclavian artery - a marker for chromosomal abnormalities?

Abstract The aberrant right subclavian artery or the aberrant right subclavian artery syndrome is a rare anatomical variant of the right subclavian artery origin but it is the most common form of congenital anomaly of the aortic arch. The normal or abnormal appearance of the aortic arch can be explained by the regression or the persistence of one or other of the two embryonic aortic arches. The regression of the right aortic arch after the origin of the right subclavian artery will result in a normal aspect of left aortic arch with normal vascular anatomy. While the right ductus arteriosus is regressing, the left one persists. This anomaly is apparently found in the general population in approximately 0.5-1.4% of the cases and in approximately 3% of cases with congenital heart malformations. The present review is focus on the prevalence of aberrant right subclavian artery in Down syndrome. Until present it is known that ultrasound evaluation in the screening programs for Down syndrome is of uncertain value and studies on larger number of cases are reconsidered. In addition we suggest that the echocardiographic examination in the first and second trimesters should be included as a first step of the diagnosis in such congenital anomalies.

Fetal Nucleic Acids in Maternal Circulation: A Genetic Resource for Noninvasive Prenatal Diagnosis

Invasive prenatal diagnosis (PND) holds a multitude of psychological considerations for women, their partners, family and community as a whole. Earlier, the non-invasive screening methods for certain disorders were serum analytes or ultrasound with low sensitivity and high false positivity. The discovery of fetal DNA in maternal plasma has opened up an approach for noninvasive PND (NIPD). Presence of fetal cells and cell-free fetal DNA (cffDNA) in the blood of pregnant women has been accepted universally and constant efforts are being made to enrich fetal DNA from maternal blood/plasma. Real-time quantitative polymerase chain reaction (qrt-PCR) has enabled fetal DNA to serve as a marker for chromosomal abnormalities, for example, trisomy 21, preterm labor, and preeclampsia. In India, PND is provided in few centers since invasive methods require trained gynecologists, this limits investigation and therefore NIPD with cffDNA from mother's blood will revolutionize fetal medicine. The present paper deals with the latest developments in procurement of cffDNA, the probable source and enrichment of fetal DNA in maternal plasma, and the current status of its detection methodologies, applications, and its potential to be used as a powerful diagnostic tool.

Ductus Venosus: A Love Story of 14 Years

ABSTRACT Ductus venosus is a tiny vessel with a central role in fetal circulation. Combining B-mode with color and pulsed Doppler is feasible to identify this vessel and evaluate the blood flow waveform at 11 to 13 weeks. The higher prevalence of abnormal A-wave in fetuses with abnormal karyotype and/or cardiac defects turned DV evaluation into a useful marker for chromosomal abnormalities and cardiopathies. Even when combined with nuchal translucency (NT) or biochemical markers, DV blood flow evaluation contributes to an increase in sensitivity and reduces false-positive rate. Abnormal ductal flow is also related to a worse fetal and perinatal outcome. In monochorionic twin pregnancies, in addition to NT measurement at 11 to 14 weeks, the Doppler assessment of DV blood flow increases relevantly the performance of screening for those at higher risk of developing twin-to-twin transfusion syndrome. This story of 14 years surely contributed to change the way first trimester screening is being implemented.

Early sonographic screening for chromosomal abnormalities

ABSTRACTThe aim of this study was to evaluate the role of prenatal markers in screening for chromosomal abnormalities at 10–16 weeks' gestation. A total of 12 107 pregnant women between 10 and 16 weeks of gestation were included. Chromosomal abnormalities were found in 126 cases. The overall detection rate, specificity and positive predictive value (PPV) for aneuploidy were 73%, 95.5% and 14.5%, respectively, when using nuchal translucency (NT) measurement as a single criterion. Using ductus venosus pulsatility index for veins (DVPIV), the overall detection rate, specificity and PPV were 73.6%, 94.8% and 12.9%, respectively. We evaluated the effectiveness of combined strategies in order to suggest the optimal policy for use in low- and high-risk populations. In our study, NT and DVPIV were the most sensitive and specific markers for chromosomal abnormalities, particularly for autosomal trisomies. In contrast, umbilical artery pulsatility index and fetal heart rate were not effective single markers for chr...

First-trimester sonographic markers for chromosomal abnormalities

(2002). First-trimester sonographic markers for chromosomal abnormalities. The Ultrasound Review of Obstetrics and Gynecology: Vol. 2, No. 4, pp. 213-220.

The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities

The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities

The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities

In a first trimester study of 5422 Caucasian women, 752 Afro-Caribbean women and 170 Asian women we have shown that the median maternal serum marker MoMs for free beta-hCG and PAPP-A were 19% and 48% higher in Afro-Caribbean women and 19% higher and 35% higher in Asian women, compared to Caucasian women. Correcting for maternal weight made very little difference to the effect in Afro-Caribbeans (21% and 57% higher after weight correction) but reduced the effect in Asians (4% and 17% higher after weight correction ). It is estimated that correcting for maternal weight and ethnicity overall would increase the detection rate by a modest 1.4%. However, the effect on an individual's risk could result in as much as a two-fold increase in the patient specific risk for trisomy 21. The impact of ethnic origin seems to be greater than that observed with second trimester biochemical markers and larger studies are required in order to develop robust algorithms for correcting for ethnic origin in the first trimester.

Influence of dietary folic acid on the developmental toxicity of methanol and the frequency of chromosomal breakage in the CD-1 mouse

The proposed increased use of methanol (MeOH)-based fuels raises the concern for an increased risk for MeOH toxicity. MeOH, which is detoxified in part via a folate-dependent pathway, is known to be teratogenic in rodents. Previous observations have implicated maternal folate status as a critical modulator for the developmental toxicity of MeOH. The current study extends these findings, examining the effect of maternal dietary folate intake on fetal folate stores, as well as identifying a possible marker for the prediction of the developmental toxicity of MeOH. Virgin female CD-1 mice were assigned to diets containing either 400 (marginal) or 1200 (control) nmol folic acid (FA)/kg, and 1% succinylsulfathiazole for 5 weeks prior to mating and throughout breeding and gestation. From gestation day (GD) 6 through 10 dams were given by gavage deionized, distilled water (dH2O) or MeOH at 2.5 g/kg body weight, twice daily. On GD 18, mice were weighed and killed and the liver, kidneys, and gravid uteri removed and weighed. Implantation sites, live and dead fetuses, and resorptions were counted; fetuses were weighed individually and examined for cleft palate and exencephaly. The marginal FA dietary treatment resulted in low maternal liver (50% reduction) and red cell folate (30% reduction) concentrations, as well as low fetal tissue folate concentrations (60 to 70% reduction) relative to the adequate FA dietary groups. Marginal FA treatment alone resulted in cleft palate in 13% of the litters; there were no litters affected with cleft palate in the adequate FA-control group. Marginal FA-MeOH treatment resulted in a further increase in the litters affected by cleft palate (72% of litters affected). The percent of litters affected by exencephaly was highest in the marginal FA-MeOH group. The frequency of micronuclei in maternal and fetal reticulocytes, a marker for chromosomal abnormalities, was not influenced by either the marginal FA diet or by MeOH treatment. These results show that marginal folate deficiency in pregnant dams significantly increases the teratogenicity of MeOH.

Fetal hyperechogenic bowel following intra-amniotic bleeding.

To test the hypothesis that increased echogenicity of the fetal bowel at second-trimester scans results from intra-amniotic bleeding. We studied 726 patients undergoing second-trimester amniocentesis for advanced maternal age. Three groups were identified according to the color of the amniotic fluid (AF) obtained: clear fluid, blood-stained fluid, and dark brown fluid. Two to 4 weeks after the amniocentesis, all patients had a targeted ultrasound examination for the detection of fetal structural anomalies and markers of chromosomal abnormalities, which included a survey of the fetal bowel. The incidence of hyperechogenic bowel in each group was compared by Fisher exact test. P < .05 was considered significant. In 694 cases, the AF was clear (95%), in 20 blood-stained (3%), and in 12 dark brown (2%). Hyperechogenic bowel was detected in 14 fetuses with clear fluid (2%), in two with blood-stained fluid (10%), and in three with dark brown fluid (25%). Fetuses with proven intra-amniotic bleeding (ie, dark brown or blood-stained AF at amniocentesis) had a significantly higher incidence of hyperechogenic bowel compared to those with clear AF (five of 32 [15.6%] and 14 of 694 [2.0%], respectively; P < .001, 95% confidence interval for the difference in proportions 6.3-17.6%). Our study demonstrates that intra-amniotic bleeding is associated with an increased incidence of fetal hyperechogenic bowel at second-trimester ultrasound scans. This sonographic phenomenon may be due to the presence of blood in the fetal bowel caused by fetal swallowing of bloody AF.