Talk:Trisomy 21

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Cite this page: Hill, M.A. (2021, July 28) Embryology Trisomy 21. Retrieved from

2011 ANAT2341 Student Comments Here

Peer review for trisomy 21

INTRODUCTION: An introduction is a brief summary of the content of the page, should only contain information that will be discussed in more detail below and not be confusing. Furthermore it should raise the interest to keep on reading. This introduction did not have this effect for me. Try to explain what trisomy 21 is about, what the characteristics are and quickly introduce the sections that will be talked about on this page. Trisomy 21 is a very common condition and we have all seen people with it on the street, it would be nice to have a picture of a person with trisomy 21 for recognition. They are lovely people and it would engage the reader. The image "Chromosome- trisomy" is a repetition of the image "Trisomy 21 (Down Syndrome) Karyotypes" and fits much better in an "etiology/pathogenesis" section, which I am hoping to find below. Links to websites with further information or to a glossary are great when they are actually directly related to the section and relevant to it. However, the introduction is rather an invitation to read more on the actual page, where the content will be discussed in detail and where links to external pages and to the glossary can be used for further information. The text itself needs proper referencing (1st and 3rd paragraph).

SOME RECENT FINDINGS: The title "recent findings" would be more appropriate under the assumption that the most recent and most relevant research is discussed here. Recent findings should rather be placed in the end of the project. The image "Trisomy 21 newborn" has no copyright information and has also no relation to this section. It neither has to do with the recent findings discussed nor is it mentioned or referred to in the text.

TRISOMY 21 (DONW SYNDROME) KARYOTYPES: The image a good illustration of what the genetic difference of an individual with trisomy 21 and a normal person is. However it could be explained more in detail. First of all if "Karyotypes" appears in the title, it should as well be explained directly in the section and not via a link to an external glossary. Secondly it would be nice to see an etiology/pathogenesis section on the page. Some one who is interested in finding out more about trisomy 21 would want to know how it is caused, what the risk factors are (eg.: the age of the mother plays and important role), and how it happens, that the genes do not separate. A suggestion would be to make an etiology/pathogenesis section and to discuss the "Trisomy 21 karyotypes" and "Meiosis I and Meiosis II" in this section. Additioinally, in the introduction it has been explained that trisomy 21 and Down's syndrome are two names for the same abnormality. Hence from that point on chose one of the names and stick with it rather that mixing them up or having the both in the same heading. The spelling in the heading is wrong (Down Syndrome, should be Down's Syndrome).

ASSOCIATED CONGENITAL ABNORMALITIES: The associated congenital abnormalities are important because they have an impact on the life of individuals with trisomy 21. Hence the section could be a little more complex. It might be worth writing an introducing paragraph, in which the most common associated abnormalities and the prevalence is mentioned. Not to forget, that the clinical picture of trisomy 21 individuals varies highly. For example there is a person that even made it into university while in more severe cases individuals only speak a few words lifelong - some individuals present with congenital heart defects some have perfectly normal hearts and no problems lifelong, etc. May be each of the relevant abnormalities could be explained in a table as under "limb defects".

AMERICAN COLLEGE: Instead of this section it would be nice to see a "diagnostic test" section. In this the "ACOG" could be incorporated as external link. The tests mentioned here for example: measuring features of the back of the neck and ultrasound are not diagnostic test for trisomy 21. Trisomy 21 is detected by sampling the amniotic fluid and by genetic testing. Abnormalities of the back of the neck and ultrasound are techniques to detect other abnormalities. Hence these are not directly relevant to trisomy 21. I have noticed that there is a complex section about screening - which discusses the detection of trisomy 21 somewhat. However I find it a little confusing. A table is a good idea but maternal age is not a procedure and what are all the tests for? Trisomy 21? How do they work? A diagram is as well and excellent idea but what does it all mean? How is a buccal swap done? And again is that all relevant to trisomy 21? If I was for example a pregnant woman with the concern that my baby has trisomy 21, I would like to know what the commonly used test is, how it is done, what the risk factors are and how accurate it is.

PREVALENCE these section would be more appropriate after the introduction, may be as "epidemiology" section. Furthermore it would be interesting the see some figures that are more recent and worldwide.

SCREENING: See comment under AMERICAN COLLEGE. Also about "SCREENING BY COUNTRY" One sentence does not need and extra heading. Either this information is not important or there could perhaps be some more information about other countries as well and about the difference such an screening makes.

MEIOSIS I AND MEIOSIS II: See comment under TRISOMY 21 (DONW SYNDROME) KARYOTYPES ANEUPLOIDY: Aneuploidy has been explained before and this section has as such no relevance to the topic.

GROWTH CHARTS: May be this information could be presented under "Clinical presentation". From this section on its own I cannot derive weather children with trisomy 21 show abnormalities in growth or not and why it should be relevant. --z3279511 15:18, 21 September 2011 (EST)

Peer review “Trisomy 21”

  • The introduction appears not quite complete.
  • The “some recent findings” section would fit better at the end of the page.
  • Adding some historic background to the page would be interesting.
  • The key points relating to the topic were well described and illustrated.
  • The choice of content shows a good understanding of the topic area.
  • Some images (e.g Human ideogram- chromosome or Chromosome trisomy) lack a reference and or copyright notice.
  • No student drawing included.
  • The term descriptions tear the page apart, they would fit better in the glossary.
  • Relates the topic and content of the Wiki entry to learning aims of embryology.
  • Use of a broad variety of reliable resources.

--Z3387190 21:41, 20 September 2011 (EST)

Peer assessment

  • I quite like the incorporated links that take you directly to the glossary, nice effect.
  • The list of links at the end of the introduction doesn’t flow very nicely. I like the idea, but maybe if you move them to the top of the page or even the bottom it would fit better.
  • The introduction could do with a bit more information and correspondence to the rest of the project.
  • The section “Some Recent Findings” would probably be better just titled “Recent Findings”, it sounds more professional. This section would also fit better at the end of the page after we know all the details of the disorder. It is too difficult to jump straight into these specifics. Also, it is a good idea, but instead of using direct quotes from the paper, a succinct summary of the research would be better. That way you could refer back to the entire page.
  • How does karyotyping work?
  • Can you elaborate on the section “associated abnormalities”? The setting is a little confusing, what disorders are you referring to? Why are they similar? Or are these a list of signs and symptoms? If so, why are they associated with the addition of an extra chromosome 21?
  • Instead of linking to the glossary, why not try to incorporate some of this information into the text?
  • Interesting information, but some of these topics can be incorporated together, ie “limb defects” and “heart defects”. Or else, add more information in each, it looks a little sparse.
  • There is no copyright information on the picture of ‘John Langdon Down’.
  • I like the idea of prevalence, this is important to give perspective to the disorder, but a more worldwide distribution would be good instead of just Ireland and USA.
  • The table in “screening” looks really good, but another column or something describing the screening techniques and details involved would be really good. The information in “novel screening strategies” sounds interesting but there needs to be more.
  • Interesting diagram for SNP screening.
  • “Screening by country” really should reference a few more countries than just spain.
  • A glossary situated directly on the page would be good, as opposed to some links to an outside glossary, and other terms defined in text ie in the “aneuploidy” section.
  • The topic and a lot of the work sounds very interesting and has the potential for a fantastic project, just a bit more content and better structured sub-headings needs to added and revised.

--Elisabeth Karsten 21:40, 18 September 2011 (EST)

Trisomy 21 assessment

  • Although it is nice that the 'nondisjunction' definition is linked to a medical dictionary, it was confusing having to scroll down to find it. It would have been easier if the link was to a page that only had the nondisjunction definition on it.
  • The introduction is very vague and does not indicate much as to what the project is about. It gives one historical reference, a definition that seems out of place and a few extra links to other genetic conditions. It would have been better to have a little more information on the actual condition rather than a definition, a few statistics and a date. Also, while the image does represent the cause of the problem, I believe it would be much more effective to have an image of a child with Trisomy 21 so that the reader is able to gauge the severity of the condition. Genetic details will (hopefully) be discussed later and this image will fit in later.
  • "recent finsings" would be better placed at the end of the project. It is difficult to understand their significance without understanding the topic
  • No historical findings are noted (other than the one date in the introduction). This should be elaborated on.
  • In the kayrotypes section, there should be an image of the normal set of chromosomes so that the reader can see the difference between that and the trisomy karyotype
  • It would also be interesting to note HOW trisomy 21 develops.
  • The list of congenital abnormalities could be expanded on to say why they are associated with trisomy 21.
  • The image in the congenital abnormalities section is not at all useful. Also, the list does not explain what the actual problems are and their significance.
  • Human idiogram-chromosome 21.jpg is not referenced
  • Heart defects need to be explained- what are they?
  • Limb abnormalities = interesting with a useful image
  • prevalence should be earlier in the project and Australia should be included in these statistics
  • The Image of Down is out of place, it has no significance here and is halfway between two sections
  • terms should be put in a glossary at the end (which is non existent)
  • the Aneuploidy section could be removed, and these terms put into a glossary instead
  • Meiosis I and Meiosis II is not a suitable heading as it does not actually explain how meiosis occurs. This information needs to be included and would be better at the top of the project
  • Overall, most of the information is present, it just needs to be rearranged into the right order.

--Sarah Jenkins 09:33, 18 September 2011 (EST)

Comments on Trisomy 21

  • The frequency of trisomy 21 in the population is approximately 1 in 650 to 1,000 live births, in Australia between 1991-97 there were 2,358 Trisomy 21 (Down) infants.: it would be better to put this statement under the heading "Prevalence".
  • It would be clearer to put the data under "Prevalence" in the form of a table.
  • The caption for the table on detection rate of various procedures, "Table data from United Kingdom" is too vague.
  • Choice of headings/sub-headings can be improved. For example, the headings, "Heart Defects" & "Limb Defects" can be sub-headings under "Associated Congenital Abnormalities".
  • The sequence of the headings can also be improved. For example, the heading "Recent Findings" should probably be one of the last few headings and should not be just after the introduction as it gives a disjointed feel to the page.
  • Reference No. 20 was not formatted properly.

--Z3389806 15:56, 18 September 2011 (EST)

Peer assessment of Trisomy 21:

  • This page covered a broad scope of information
  • Lots of relevant links if more information was wanted
  • Not sure of the set out of headings, it seemed like there could have been a better order of topics
  • Formatting gaps tended to disrupt the flow of the page
  • The “some recent findings” was an interesting topic, however I think that instead of quotes being used, that maybe a more concise summary for each could have been formulated.
  • Sounds silly, but grammatically errors were noticed such as lower case letters beginning dot points.
  • Prevalence of more than 2 countries probably could have been used.
  • Good use of a broad range of references

--Ashleigh Pontifex 08:37, 20 September 2011 (EST)

Peer Assessment: Trisomy 21

  • The uncommon words linked straight to the glossary, for example nondisjunction, make the article more accessible and easier to read for the general population.
  • The sentence explaining aneuploidy in the introduction is unnecessary and/or wrongly placed. Either the definition should be given in the first sentence that you use aneuploidy, in the section on aneuploidy or the uncommon word linked to glossary formatting should be used again.
  • The word screening is probably common enough that you do not need to link it to the glossary.
  • The last two sentences of the introduction do not flow very well - the first sentence regarding recent literature would probably be better used as an introductory sentence in the some recent findings section.
  • The some recent findings section might be better placed towards the end of the page with the meiosis I and II and growth chart sections. Instead background information could be placed at the beginning.
  • The articles in the some recent findings section are informative and well referenced. They could be summarised in your own words.
  • There is a lack of referencing for some of the information in sections: associated congenital abnormalities, heart defects, detection using tandem single nucleotide polymorphisms and aneuploidy.
  • Citation number 6 and 9 are not properly referenced. More information should be given - see the UNSW referencing webpage.
  • It is good that a number of sections include external links where more information can be found.
  • There is a good amount of images, however some of them could be placed more appropriately. For example the photograph of John Down could be placed adjacent to the introduction section as he is mentioned there.
  • For all images and figures copyright information should be given on the image file page - this has not been completed for the first image and a number of other ones.

--z3217345 12:39, 20 September 2011 (EST)

Peer Review Trisomy 21

The overview

  • Good use of headings, structure seems to be a little mixed. Maybe start with board heading the subdheadings to beak up the writing and make it easy to understand.
  • Illustration and text ratio was nice not to heavy on either. No student drawing.
  • Would have been nice to add a genetics heading rather then just linking to different pages. This looks strange at the top.. maybe rethink position. Trisomy Karyotypes could have been added here.
  • Some words are not included in glossary eg AMH acronyms must be explained
  • some pictures seem to be muddle eg the picture of Down himself would have fit nicely in the intro..
  • many aspects of the page are not cited. This would give you page more credibility.
  • Detection using Tandem Single Nucleotide Polymorphisms image. Consider resizing as it is very large.


  • The first sentence is a little to wordy, as introduction should be punchy and to the point. Maybe try and re-word

Down syndrome or trisomy 21 is caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal and is one of the most common chromosomal abnormalities in liveborn children. Maybe.. The most common chromosomal abnormality occurring in live births is Down syndrome, otherwise known as Trisomy 21. This syndrome is caused by the nondisjustion of the 21st chromosome, in which there is the partial or whole presence of an extra chromosome.

  • The history of Down syndrome would be a nice extra such as when the chromosome was identified.

Also rewording of the sentence Down Syndrome is the historic name used for this condition identified by Down, J.L.H. in a 1866 paper where he described the "phenotypic features that includes mental retardation and characteristic facies". Such as, In 1866 John Langdon Down identified and described some of his patients who he said to have "phenotypic features that includes mental retardation and characteristic facies". Due to his historic findings this syndrome now bares Downs’ name. Reference?

Recent Findings

• In recent findings it might be nice to summaries the paper rather then quote directly from it. Some things are difficult to understand and I don’t quite get the gist of what is actually being done. • I like the link to PubMed- great thinking.

Associated Congenital Abnormalities • good use of bullet point maybe have been nice to illustrate abnormalities with pictures.

Heart Defects

  • I like the of percentages but where were these numbers generated from? No reference??
  • Good use of links here.

Limb Defects could have had major head “defects” then use subheading to differentiate limb and heart. The use of references should accompany statistics.

American College of Obstetricians and Gynecologists Recommendations

  • interesting choice, would have been nice to see in own words not just copy and pasted.

Prevalence • May fit in nicer near the intro, as readers are generally very interested in this part. • Good to see the use of references

Down's syndrome Screening

  • Great use of table and stats.

--z3294943 14:51, 20 September 2011 (EST)

Peer review Trisomy 21

  • The introduction could be a little bit longer, and maybe include a little bit of a historic timeline?
  • Having the recent findings follow the introduction immediately is confusing as the reader hasn't had a chance to learn anything about the condition yet, so can't really relate the recent findings to anything.
  • A broad range of topics is covered which is good, but there doesn't seem to be a logical structure to it - things don't lead on from each other.
  • The links to further external resources are a very good idea, and there are a lot of them, which is good and makes it easy to find out more and get a deeper understanding. Including these links also makes the page itself less crowded and helps keep a good overview.
  • The mere use of bullet points in most parts does keep things simple and clear, but also partly gives an impression of lack of depth. Certain points could be explained in a little bit more detail.
  • The table that is used for Screening Strategies is an efficient way of showing the data, though I don't quite understand what the "maternal age" screening procedure is, and how that can have a detection rate? I assume it relates to the fact that older mothers have a higher risk of bearing Down Syndrome children, but what exactly is the screening procedure?
  • Though the terms are explained in "detection using tandem nucleotide repeats", the section is still too technical. It doesn't explain why this technique allows the detection of the trisomy 21. For somebody who isn't familiar with genetics, it is very hard to understand. I am familiar with genetics, but the sentence "Tandem SNP sequences identified as heterozygous on maternal buccal swab are amplified on maternal plasma by ..." doesn't quite make sense to me - how can the sequences be amplified ON the maternal plasma?
  • Listing the screening by country is a good idea, but then should contain more than just information for 1 country.
  • Generally, there is a curious mix of very well explained terms and sections, and sections that still seem incomplete.

--z3389343 19:56, 20 September 2011 (EST)

Peer Assessment

  • The introduction is good
  • There are a lot of subheadings, maybe some of them could be combined
  • Recent findings might be better towards the end of the page
  • The links at the end of the subheadings are good
  • The "Screening by Country" section should contain more than one country
  • The Prevalence section could also use more examples
  • Some of the images need to be properly referenced
  • It may have been good to include some backgorund information
  • Some of the images, especially the John Down one, didnt seem to fit in the section where they were placed and would be bettter used somewhere more relevent.

--z3292953 12:15, 21 September 2011 (EST)


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.


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


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.


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.


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.


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

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. 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]
  1. <pubmed>18681837</pubmed>
  2. <pubmed>18677711</pubmed>


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. 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

Discovery of novel serum biomarkers for prenatal Down syndrome screening by integrative data mining


"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


Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice


"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.

PMCID: PMC2657943

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."


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. 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. 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