Talk:Trisomy 21
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Cite this page: Hill, M.A. (2024, June 2) Embryology Trisomy 21. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Trisomy_21 |
2011
Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma
PLoS One. 2011;6(11):e27709. Epub 2011 Nov 23.
Lim JH, Kim SY, Park SY, Lee SY, Kim MJ, Han YJ, Lee SW, Chung JH, Kim MY, Yang JH, Ryu HM. Source Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea. Abstract BACKGROUND: Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A. METHODOLOGY/PRINCIPAL FINDINGS: A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively. CONCLUSIONS: Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.
PMID 22132128
Introduction of first trimester combined test increases uptake of Down's syndrome screening
Eur J Obstet Gynecol Reprod Biol. 2011 Aug 10.
Tringham GM, Nawaz TS, Holding S, McFarlane J, Lindow SW. Source Hull York Medical School, Hertford Building, University of Hull, Kingston upon Hull, UK.
Abstract
OBJECTIVE: To describe any trends in the uptake of antenatal screening for Down's syndrome since the addition of the earlier first trimester combined test.
STUDY DESIGN: All antenatal screening tests for Down's syndrome were carried out and their results were recorded by the Clinical Biochemistry Department at the Hull Royal Infirmary (HRI) and reviewed against the antenatal booking data held at the Women and Children's Hospital at HRI. The uptake of antenatal Down's syndrome screening for 5 different age groups of women across a four-year-period from 2007 to 2010 was analysed.
RESULTS: There was a significant increase in uptake of antenatal screening for Down's syndrome from 43.9% to 56.5% after the introduction of the combined test in 2010. This increase was apparent in all age groups. There was no change in the proportion of women opting for an invasive test following a positive screening test.
CONCLUSION: Addition of the earlier first trimester combined test has increased uptake of antenatal screening for Down's syndrome in women of all ages. This is most likely due to the advantages this test gives women such as earlier decision making, earlier further invasive diagnostic testing and earlier termination, if necessary.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PMID 21839574
2010
Learning curve in measurement of fetal frontomaxillary facial angle at 11-13 weeks of gestation
Ultrasound Obstet Gynecol. 2010 May;35(5):530-4.
Yang X, Chen M, Wang HF, Leung TY, Borenstein M, Nicolaides K, Sahota DS, Lau TK. Source Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Abstract
OBJECTIVE: To determine the number of ultrasound examinations required to train sonographers to accurately measure the fetal frontomaxillary facial (FMF) angle at 11-13 weeks of gestation.
METHODS: Eight sonographers accredited for nuchal translucency thickness (NT) measurement (and with different levels of experience) were trained to measure the fetal FMF angle using specially acquired three-dimensional (3D) volumes. Training was provided in cycles, and each cycle consisted of a training period on 20 randomly selected cases followed by an examination using 10 randomly selected cases. During training, the sonographer was informed of the true FMF angle value after each FMF angle measurement on a case-by-case basis. During examination, the difference between the measured and the true values of the FMF angle (i.e. the delta angle) was calculated. A measurement was considered accurate if the delta angle was less than 5 degrees . The sonographer was considered to be competent and the training finished if all 10 examination cases satisfied this criterion. Otherwise, the sonographer would undergo further cycles of training-examination, until he/she became competent.
RESULTS: The number of training cases required for a sonographer to become competent was 40 for two sonographers, 60 for one, 80 for one, 100 for two, 120 for one and 140 for one, with a median of 90. The median number of failed cases reduced from 2.5 (out of 10) at the first cycle to 0 by the 7(th) cycle. As training cycles increased, the mean angle deviation and measurement time required both reduced significantly. The average delta angle of the passing examination cycle was 2.06 +/- 1.40 degrees . The number of training cases required to become competent in FMF angle measurement was 40 for the two most experienced trainees and 80, 120 and 140 for the three least experienced ones.
CONCLUSIONS: We have demonstrated that competence in FMF angle measurement was achieved after a median number of 90 cases, with a range of up to 140. The number required was substantially lower, at 40 cases, among those with extensive experience of NT measurement.
Copyright 2010 ISUOG. Published by John Wiley & Sons, Ltd.
PMID 20127748
Maternal antimullerian hormone levels do not predict fetal aneuploidy
J Assist Reprod Genet. 2010 Jul;27(7):409-14. Epub 2010 May 20.
Plante BJ, Beamon C, Schmitt CL, Moldenhauer JS, Steiner AZ. Source The University of North Carolina School of Medicine, Department of Obstetrics and Gynecology, Chapel Hill, 27599-7570, USA. bethplante@gmail.com
Abstract
PURPOSE: To determine if diminished ovarian reserve (measured by maternal antimullerian hormone (AMH) levels), is associated with fetal aneuploidy (determined by prenatal karyotype).
METHODS: This case-control study included 213 women with singleton pregnancies who underwent both serum aneuploidy screening and invasive prenatal diagnosis. 18 patients carrying an aneuploid fetus served as cases and the remaining 195 women with a euploid fetus were controls. Serum AMH was measured using two assays: AMHbc (Beckman-Coulter) and AMHdsl (Diagnostic Systems Laboratories). Karyotypes were determined by chorionic villus sampling or amniocentesis.
RESULTS: AMHbc levels did not differ between women with an aneuploid fetus and women with a euploid fetus (p = 0.46) and did not predict aneuploidy (ROC Area = 0.57). Additionally, AMHbc values declined significantly with advancing gestational age.
CONCLUSIONS: Maternal AMH does not appear to be a marker of fetal aneuploidy in ongoing pregnancies. Contrary to previous reports, we found a significant decline in maternal AMH levels with advancing gestational age.
PMID 20490648
First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker
Reprod Biol Endocrinol. 2010 Oct 29;8:129.
Tørring N, Ball S, Wright D, Sarkissian G, Guitton M, Darbouret B. Department of Clinical Biochemistry, Aarhus University Hospital-Skejby, Aarhus, Denmark. nto@ki.au.dk
Abstract
BACKGROUND: A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model.
METHOD: In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model.
RESULTS: The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP-A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free β-hCG with or without nuchal translucency.
CONCLUSION: The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.
PMID: 21034452 http://www.ncbi.nlm.nih.gov/pubmed/21034452
http://www.rbej.com/content/8/1/129
Prenatal sonographic features of fetuses in trisomy 13 pregnancies. IV
Taiwan J Obstet Gynecol. 2010 Mar;49(1):3-12.
Chen CP.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com Abstract Prenatal ultrasound is a powerful tool to detect structural abnormalities associated with the fetuses in trisomy 13 pregnancies. This article provides a comprehensive review of the prenatal sonographic markers of trisomy 13 in the first trimester, including fetal nuchal translucency thickness, fetal heart rate, fetal nasal bone, fetal tricuspid regurgitation, ductus venous flow, fetal crown-rump length, fetal trunk and head volume, fetal frontomaxillary facial angle, gestational sac volume and umbilical cord diameter, along with biochemical markers such as maternal serum free beta-human chorionic gonadotropin, maternal serum pregnancy-associated plasma protein-A, maternal serum placental growth factor, and the fetal and total cell-free DNA concentration in the maternal circulation.
PMID: 20466286
Novel Screening Strategies
There are several additional suggested screeening stratagies currently at various stages of development. These techniques should be seen as at the research stage olny until data, a clinical concensus and a recommendation has been made.
- Odibo AO, Sehdev H, Stamilio DM, Macones GA. OC053: The efficiency of second-trimester nasal bone (NB) hypoplasia as a Down syndrome marker in low versus high-risk groups. Ultrasound Obstet Gynecol. 2008 Aug 11;32(3):259-260. PMID: 18697081
- van Heesch PN, Struijk PC, Brandenburg H, Steegers EA, Wildschut HI. Jugular lymphatic sacs in the first trimester of pregnancy: the prevalence and the potential value in screening for chromosomal abnormalities. J Perinat Med. 2008 Aug 6. PMID: 18681837
- Calda P, Belosovicova-Viskova H, Valtrova H, Svabik K, Manasova S, Zizka Z, Brestak M, Nekovarova K. OC052: Ultrasound at 20-22 weeks of pregnancy increases the rate of detection of Down syndrome above that of combined first-trimester screening alone. Ultrasound Obstet Gynecol. 2008 Aug 11;32(3):259. PMID: 18697054
- Kirkegaard I, Petersen OB, Uldbjerg N, Turring N. Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks. Prenat Diagn. 2008 Aug 1. PMID: 18677711
Novel Screening Strategies
There are several additional suggested screeening stratagies currently at various stages of development. These techniques should be seen as at the research stage only until data, a clinical concensus and a recommendation has been made.
- Jugular lymphatic sacs in the first trimester of pregnancy [1]
- First-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks [2]
- The National Down Syndrome Project: Design and Implementation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1802119/
2009
Increased prevalence of renal and urinary tract anomalies in children with Down syndrome
Pediatrics. 2009 Oct;124(4):e615-21. Epub 2009 Sep 14.
Kupferman JC, Druschel CM, Kupchik GS. Source Divisions of Pediatric Nephrology and Hypertension, Maimonides Infants and Children's Hospital, Brooklyn, New York 11219, USA. jkupferman@maimonidesmed.org Abstract OBJECTIVE: The goal was to investigate the prevalence of renal and urinary tract anomalies (RUTAs) in a Down syndrome (DS) population.
METHODS: Data were obtained from the New York State Congenital Malformation Registry (NYS-CMR) in this retrospective cohort study. The occurrence of RUTAs was assessed for children with and without DS who were born in NYS between 1992 and 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each malformation.
RESULTS: Between 1992 and 2004, 3832 children with DS and 3 411 833 without DS were born in NYS. The prevalence of RUTAs in the DS population was 3.2%, compared with 0.7% in the NYS population (OR: 4.5 [95% CI: 3.8 -5.4]). Children with DS had significantly increased risks of anterior urethral obstruction (OR: 29.7 [95% CI: 4.0 -217.7]), cystic dysplastic kidney (OR: 4.5 [95% CI: 1.5-14.1]), hydronephrosis (OR: 8.7 [95% CI: 6.8 -11.0]), hydroureter (OR: 8.5 [95% CI: 3.5-20.4]), hypospadias (OR: 2.0 [95% CI: 1.4 -2.9]), posterior urethral valves (OR: 7.1 [95% CI: 1.8 -28.8]), prune belly syndrome (OR: 11.9 [95% CI: 1.6 - 85.4]), and renal agenesis (OR: 5.4 [95% CI: 2.8 -10.4]). There was no significantly increased risk of ectopic kidney (OR: 1.6 [95% CI: 0.2-11.2]) or ureteropelvic junction obstruction (OR: 1.4 [95% CI: 0.2-9.9]) in the DS population.
CONCLUSION: Children with DS have significantly increased risks of RUTAs.
PMID: 19752083 http://www.ncbi.nlm.nih.gov/pubmed/19752083
Discovery of novel serum biomarkers for prenatal Down syndrome screening by integrative data mining
<pubmed>19956656</pubmed>
"To facilitate the experimental search for novel maternal serum biomarkers in prenatal Down Syndrome screening, we aimed to create a set of candidate biomarkers using a data mining approach."
Down syndrome—recent progress and future prospects
<pubmed>19297404</pubmed>
Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice
<pubmed>19617567</pubmed>
"Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here, we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice and that the effect increases with advancing maternal age."
Down syndrome—recent progress and future prospects
Frances K. Wiseman, Kate A. Alford, Victor L.J. Tybulewicz, and Elizabeth M.C. Fisher Hum Mol Genet. 2009 April 15; 18(R1): R75–R83. doi: 10.1093/hmg/ddp010.
Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice
Leland S, Nagarajan P, Polyzos A, Thomas S, Samaan G, Donnell R, Marchetti F, Venkatachalam S. Proc Natl Acad Sci U S A. 2009 Jul 17. PMID: 19617567
- "Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here, we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice and that the effect increases with advancing maternal age."
2008
Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A
Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH. Hum Reprod. 2008 Sep;23(9):1968-75. Epub 2008 Jun 10. PMID: 18544579
Frequency and distribution of chromosome abnormalities in human oocytes
Cytogenet Genome Res. 2005;111(3-4):193-8.
Kuliev A, Cieslak J, Verlinsky Y.
Reproductive Genetics Institute, Chicago, IL 60614, USA. anverkuliev@hotmail.com Abstract It was previously shown that more than half of the human oocytes obtained from IVF patients of advanced reproductive age are aneuploid, due to meiosis I and meiosis II errors. The present paper further confirms that 61.8% of the oocytes tested by fluorescent probes specific for chromosomes 13, 16, 18, 21 and 22 are abnormal, representing predominantly chromatid errors, which are the major source of aneuploidy in the resulting embryos. Almost half of the oocytes with meiosis I errors (49.3%) are prone to sequential meiosis II errors, which may lead to aneuploidy rescue in 30.8% of the cases. Half of the detected aneuploidies (49.8%) are of complex nature with involvement of two or more chromosomes, or the same chromosome in both meiotic divisions. The aneuploidy rates for individual chromosomes are different, with a higher prevalence of chromosome 21 and 22 errors. The origin of aneuploidy for the individual chromosomes is also not random, with chromosome 16 and 22 errors originating more frequently in meiosis II, and chromosome 18, 13 and 21 errors in meiosis I. There is an age dependence not only for the overall frequency of aneuploidies, but also for each chromosome error, aneuploidies originating from meiosis I, meiosis II, and both meiosis I and meiosis II errors, as well as for different types of aneuploidies. The data further suggest the practical relevance of oocyte aneuploidy testing for detection and avoidance from transfer of the embryos deriving from aneuploid oocytes, which should contribute significantly to the pregnancy outcomes of IVF patients of advanced reproduction age.
PMID: 16192694
Impact of trisomy on fertility and meiosis in male mice
Hum Reprod. 2007 Feb;22(2):468-76. Epub 2006 Oct 17. Davisson M, Akeson E, Schmidt C, Harris B, Farley J, Handel MA.
The Jackson Laboratory, Bar Harbor, ME 04609, USA. muriel.davisson@jax.org Abstract BACKGROUND: Chromosomal abnormalities frequently are associated with impairment or arrest of spermatogenesis in mammals but are compatible with fertility in female carriers of the same anomaly. In the case of trisomy, mice have extra genomic DNA as well as the chromosomal abnormality, usually present as an extra, unpaired chromosome. Thus, impairment of spermatogenesis in trisomic males could be due to the presence of extra genomic material (i.e. triplicated genes) or due to the chromosomal abnormality and presence of an unpaired chromosome in meiosis.
METHODS: In this study, fertility and chromosomal pairing configurations during meiotic prophase were analysed in male mice trisomic for different segments of the genome. Four have an extra segmental or tertiary trisomic chromosome--Ts(17(16))65Dn, Ts(10(16))232Dn, Ts(12(17))4Rk and Ts(4(17))2Lws--and one has the triplicated segment attached to another chromosome--Ts(16C-tel)1Cje. Ts(17(16))65Dn and Ts(16C-tel)1Cje have similar gene content triplication and differ primarily in whether the extra DNA is in an extra chromosome or not.
RESULTS: The presence of an intact extra chromosome, rather than trisomy per se, is associated with male sterility. Additionally, sterility is correlated with a high frequency of association of the unpaired chromosome with the XY body, which contains the largely unpaired X and Y chromosomes.
CONCLUSIONS: Intact extra chromosomes disrupt spermatogenesis, and unpaired chromosomes establish a unique chromatin territory within meiotic nuclei.
PMID: 17050550
Trisomy 21 enhances human fetal erythro-megakaryocytic development
Chou ST, Opalinska JB, Yao Y, Fernandes MA, Kalota A, Brooks JS, Choi JK, Gewirtz AM, Danet-Desnoyers GA, Nemiroff RL, Weiss MJ. Blood. 2008 Dec 1;112(12):4503-6. PMID: 18812473
"Children with Down syndrome exhibit 2 related hematopoietic diseases: transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). Both exhibit clonal expansion of blasts with biphenotypic erythroid and megakaryocytic features and contain somatic GATA1 mutations. ...Our findings indicate that trisomy 21 itself is associated with cell-autonomous expansion of erythro-megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the pool of cells susceptible to malignant transformation through acquired mutations in GATA1 and other cooperating genes."
Kirkegaard I, Petersen OB, Uldbjerg N, T√∏rring N. Abstract Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks.Prenat Diagn. 2008 Aug 1. [Epub ahead of print]
Breathnach FM, Malone FD. Screening for aneuploidy in first and second trimesters: is there an optimal paradigm? Curr Opin Obstet Gynecol. 2007 Apr;19(2):176-82.
"Screening strategies for aneuploidy continue to evolve, with the most recent evidence favouring a contingent sequential approach."
American College of Obstetricians and Gynecologists New Recommendations for Down Syndrome Call for Screening of All Pregnant Women (January 2, 2007) (More? [#ACOGrecommendations ACOG Screening Recommendations])
"This new recommendation says that the maternal age of 35 should no longer be used by itself as a cut-off to determine who is offered screening versus who is offered invasive diagnostic testing"
Akiyama T, Nagata M, Aoki F. Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice. Proc Natl Acad Sci U S A. 2006 May 1;
"It was recently reported that histones are globally deacetylated in mammalian oocytes during meiosis but not mitosis. ... The high incidence of aneuploidy in the embryos of older females may be due to inadequate meiotic histone deacetylation."
Prenatal Diagnosis
Chitty LS, Kagan KO, Molina FS, Waters JJ, Nicolaides KH. Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study. BMJ. 2006 Feb 13
Trisomy 21--z3330313 00:23, 22 September 2011 (EST)
-Introduction: Does cover details of the disorder briefly however the format did not flow because for some of the information written it looked as though it belonged to the glossary section of the page. But there was a good use of external links
-Some recent findings: Regarding the flow of the page the next sub heading did not fit. It would be more appealing if the "some recent findings" heading were to be loacted near the end of the page. However, the information was written very well and easy to read/condensed.
-Trisomy 21 (Down Syndrome) Karyotypes : The use of images is to be congratulated, it is a helpful visual aid. However, the use of good image was not taken advantage of in written form. The information written was limited and too brief, the writer relied on the image too much.
-Associated Congenital Abnormalities: This section had a list of the abnormalities however that was just it. There was no explanation of what type of disorder it is or any description what so ever. This section is somewhat of an important sub heading as it deals with abnormal changes to the embryo or fetus during development but the writer only left a brief note which only shows laziness.
-Heart Defect: Very good use of statistics and external links to help the reader understand the information laid out. Most words were hyperlinked to the glossary section, maybe instead of doing that the writer could just incorpate the information into the main text because it is not just one word but a few thus it would be easier to read it in one go also these words are bulletpointed anyways.
-Limb Defects: Good use of external links again and a nice image but why not conbine the previous subheading into one heading as, "DEFECTS" because they were both short pieces of information and they both relate to the same topic so it would thus look more appealing and less spaced.
-It would be a suggestion to have a subheading as "epidemiology" so not only information on prevalence will be covered but also statistics on rate of incidence etc.. and why it is occurring at that rate. Furthermore, if Australian statistics were to be used than that would be fantastic as it would be more relevant to us.
-The reference list was good. It was categorised into the different types of sources used. A good job!
--z3330313 00:23, 22 September 2011 (EST)
