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| #REDIRECT ] | |||
| {{DiseaseDisorder infobox | | |||
| Name = Down syndrome | | |||
| ICD10 = {{ICD10|Q|90||q|90}} | | |||
| ICD9 = {{ICD9|758.0}} | | |||
| ICDO = | | |||
| Image = Drill.jpg <!--- Do not change this picture without discussing it in the Down syndrome discussion page. Because of continued vandalism, pictures will be immediately reverted. ---> | | |||
| Caption = Boy with Down syndrome using an electric screwdriver| | |||
| OMIM = 190685 | | |||
| OMIM_mult = | | |||
| MedlinePlus = 000997 | | |||
| eMedicineSubj = ped | | |||
| eMedicineTopic = 615 | | |||
| DiseasesDB = 3898 | | |||
| MeshID = D004314 | | |||
| }} | |||
| '''Down syndrome''' or '''trisomy 21''' (usually '''Down's Syndrome''' in British English<ref>{{cite web|url=http://www.ds-health.com/trisomy.htm |title=Trisomy 21: The Story of Down Syndrome paper}}</ref>) is a ] caused by the presence of all or part of an extra ]. It is named after ], the British doctor who described it in ]. The disorder was identified as a chromosome 21 trisomy by ] in 1959. The condition is characterized by a combination of major and minor differences in body structure. Often Down syndrome is associated with some impairment of ] ability and ] as well as facial appearance. Down syndrome can be identified during pregnancy or at birth. | |||
| Individuals with Down syndrome can have a lower than average cognitive ability, often ranging from mild to moderate ]. Developmental disabilities often manifest as a tendency toward concrete thinking or ]. A small number have severe to profound mental retardation. The ] of Down syndrome is estimated at 1 per 800 to 1,000 births. | |||
| Many of the common physical features of Down syndrome also appear in people with a standard set of chromosomes. They include a ] (a single instead of a double crease across one or both palms), an almond shape to the eyes caused by an ] of the eyelid, shorter limbs, poor muscle tone, a larger than normal space between the big and second toes, and protruding tongue. Health concerns for individuals with Down syndrome include a higher risk for ]s, ], recurrent ], ], and ] dysfunctions. | |||
| ], screening for common problems, medical treatment where indicated, a conducive family environment, and vocational training can improve the overall development of children with Down syndrome. Although some of the physical genetic limitations of Down syndrome cannot be overcome, education and proper care will improve quality of life.<ref>Roizen NJ, Patterson D.''Down's syndrome.'' Lancet. 2003 ];361(9365):1281–9. Review. PMID 12699967</ref> | |||
| ==Characteristics== | |||
| ] known as '']'']] | |||
| Individuals with Down syndrome may have some or all of the following physical characteristics: oblique eye fissures with ]s on the inner corner of the eyes, ] (poor muscle tone), a flat nasal bridge, a ] (also known as a simian crease), a protruding tongue (due to small oral cavity, and an enlarged tongue near the tonsils), a short neck, white spots on the ] known as ],<ref>{{cite web |url=http://www.medterms.com/script/main/art.asp?articlekey=6570 |title=Definition of Brushfield's Spots}}</ref> excessive flexibility in joints, ]s, excessive space between ] and second toe, a single ] furrow of the fifth finger, and a higher number of ulnar loop ]. Most individuals with Down syndrome have ] in the mild (] 50–70) to moderate (IQ 35–50) range,<ref>{{cite web |url=http://www.keepkidshealthy.com/welcome/conditions/downsyndrome.html |title=Keep Kids Healthy article on Down syndrome |accessedate=2006-04-10}}</ref> with scores of children having Mosaic Down syndrome (explained below) typically 10–30 points higher.<ref>{{cite web |author=Strom, C |url=http://www.mosaicdownsyndrome.com/faqs.htm |title=FAQ from Mosaic Down Syndrome Society |accessdate = 2006-06-03}}</ref> In addition, individuals with Down syndrome can have serious abnormalities affecting any body system. | |||
| ==Genetics== | |||
| {{main|Genetic origins of Down syndrome}} | |||
| ] for trisomy Down syndrome. Notice the three copies of chromosome 21]] | |||
| Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the ], either in whole (] 21) or part (such as due to ]). The effects of the extra copy vary greatly among individuals, depending on the extent of the extra copy, genetic background, environmental factors, and random chance. Down syndrome occurs in all human populations, and analogous effects have been found in other species such as chimpanzees<ref>McClure HM, Belden KH, Pieper WA, Jacobson CB. Autosomal trisomy in a chimpanzee: resemblance to Down's syndrome. ''Science.'' 1969 ];165(897):1010–2. PMID 4240970</ref> and mice. Recently, researchers have created ] mice with most of human chromosome 21 (in addition to the normal mouse chromosomes).<ref>{{cite web |url=http://news.bbc.co.uk/1/hi/health/4268226.stm |title=Down's syndrome recreated in mice| publisher=BBC News |accessdate = 2006-06-14 |date=2005-09-22}}</ref> The extra chromosomal material can come about in several distinct ways. A typical human karyotype is designated as 46,XX or 46,XY, indicating 46 chromosomes with an XX arrangement typical of females and 46 chromosomes with an XY arrangement typical of males.<ref>For a description of human karyotype see {{cite web |author=Mittleman, A. (editor) |year=1995 |url=http://www.iscn1995.org/ |title=An International System for Human Cytogenetic Nomeclature |accessdate = 2006-06-04}}</ref> | |||
| ===Trisomy 21=== | |||
| Trisomy 21 (47,XX,+21) is caused by a ] ] event. With nondisjunction, a ] (''i.e.'', a sperm or egg cell) is produced with an extra copy of chromosome 21; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the ] now has 47 chromosomes, with three copies of chromosome 21. Trisomy 21 is the cause of approximately 95% of observed Down syndromes, with 88% coming from nondisjunction in the maternal gamete and 8% coming from nondisjunction in the paternal gamete.<ref name="occurrence">{{cite web |url=http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#TheOccurrence |title=Down syndrome occurrence rates (NIH) |accessdate = 2006-06-02}}</ref> | |||
| ===Mosaicism=== | |||
| Trisomy 21 is caused prior to conception, and all cells in the body are affected. However, when some of the cells in the body are normal and other cells have trisomy 21, it is called ] Down syndrome (46,XX/47,XX,+21).<ref></ref> This can occur in one of two ways: A ] event during an early cell division in a normal embryo leads to a fraction of the cells with trisomy 21; or a Down syndrome embryo undergoes nondisjunction and some of the cells in the embryo revert to the normal chromosomal arrangement. There is considerable variability in the fraction of trisomy 21, both as a whole and among tissues. This is the cause of 1–2% of the observed Down syndromes.<ref name="occurrence" /> | |||
| ===Robertsonian translocation=== | |||
| The extra chromosome 21 material that causes Down syndrome may be due to a ]. In this case, the long arm of chromosome 21 is attached to another chromosome, often ] (45,XX, t(14;21q)) or itself (called an ], 45,XX, t(21q;21q)). Normal ]s leading to gametes have a significant chance of creating a gamete with an extra chromosome 21. Translocation Down syndrome is often referred to as ''familial Down syndrome''. It is the cause of 2–3% of observed cases of Down syndrome.<ref name="occurrence" /> It does not show the maternal age effect, and is just as likely to have come from fathers as mothers. | |||
| ===Duplication of a portion of chromosome 21=== | |||
| Rarely, a region of chromosome 21 will undergo a duplication event. This will lead to extra copies of some, but not all, of the genes on chromosome 21 (46,XX, dup(21q)).<ref>Petersen MB, Tranebjaerg L, McCormick MK, Michelsen N, Mikkelsen M, Antonarakis SE. ''Clinical, cytogenetic, and molecular genetic characterization of two unrelated patients with different duplications of 21q.'' Am J Med Genet Suppl. 1990;7:104-9. | |||
| PMID 2149934</ref> If the duplicated region has genes that are responsible for Down syndrome physical and mental characteristics, such individuals will show those characteristics. This cause is very rare and no rate estimates are available. | |||
| ==Incidence== | |||
| ] | |||
| The incidence of Down syndrome is estimated at 1 per 800 to 1 per 1000 births.<ref name=NIHestimates>Based on estimates by National Institute of Child Health & Human Development {{cite web| title = Down syndrome rates| url=http://web.archive.org/web/20060901004316/http://www.nichd.nih.gov/publications/pubs/downsyndrome/down.htm#Questions| accessdate = 2006-06-21}} | |||
| </ref> In 2006, the Center for Disease Control estimated the rate as 1 per 733 live births in the United States (5429 new cases per year).<ref>{{cite journal |author=Center for Disease Control |title=Improved National Prevalence Estimates for 18 Selected Major Birth Defects, United States, 1999–2001 |journal=Morbidity and Mortality Weekly Report |volume=54 |issue=51 & 52 |date=] ]| url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5451a2.htm| pages=1301–1305}}</ref> Approximately 95% of these are ] 21. Down syndrome occurs in all ethnic groups and among all economic classes. | |||
| ] influences the chances of conceiving a baby with Down syndrome. At maternal age 20 to 24, the probability is 1/1490; at age 40 the probability is 1/60, and at age 49 the probability is 1/11.<ref name=Hook/> Although the probability increases with maternal age, 80% of children with Down syndrome are born to women under the age of 35,<ref>Estimate from {{cite web |title=National Down Syndrome Center |url=http://www.ndsccenter.org/resources/package3.php |accessdate = 2006-04-21}}</ref> reflecting the overall fertility of that age group. Other than maternal age, no other risk factors are known. There does not appear to be a paternal age effect. | |||
| ==Prenatal screening== | |||
| Pregnant women can be screened for various complications during pregnancy. Many standard prenatal screens can discover Down syndrome. ] along with ], such as ], ] (CVS), or percutaneous umbilical blood sampling (PUBS) are usually offered to families who may have an increased chance of having a child with Down syndrome, or where normal prenatal exams indicate possible problems. Genetic screens are often performed on pregnant women older than 30 or 35. | |||
| Amniocentesis and CVS are considered invasive procedures, in that they involve inserting instruments into the uterus, and therefore carry a small risk of causing fetal injury or miscarriage. There are several common non-invasive screens that can indicate a fetus with Down syndrome. These are normally performed in the late first trimester or early second trimester. Due to the nature of screens, each has a significant chance of a ], suggesting a fetus with Down syndrome when, in fact, the fetus does not have this genetic abnormality. Screen positives must be verified before a Down syndrome diagnosis is made. Common screening procedures for Down syndrome are given in Table 1. | |||
| {| class="wikitable" | |||
| |+ Table 1: Common first and second trimester Down syndrome screens | |||
| |- | |||
| !Screen | |||
| !When performed (weeks ]) | |||
| !Detection rate | |||
| !] rate | |||
| !Description | |||
| |- | |||
| |Triple screen | |||
| |align="center"|15–20 | |||
| |align="center"|75% | |||
| |align="center"|8.5% | |||
| |This test measures the maternal serum ] (a fetal liver protein), ] (a pregnancy hormone), and ] (hCG, a pregnancy hormone).<ref name=quadrate>For a current estimate of rates, see {{cite journal| author=Benn, PA, J Ying, T Beazoglou, JFX Egan| journal=Prenatal Diagnosis| volume=21| issue=1| pages=46–51| title=Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustments for cross-identification and double-positive results}} PMID 11180240</ref> | |||
| |- | |||
| |Quad screen | |||
| |align="center"|15–20 | |||
| |align="center"|79% | |||
| |align="center"|7.5% | |||
| |This test measures the maternal serum ] (a fetal liver protein), ] (a pregnancy hormone), ] (hCG, a pregnancy hormone), and high ]-Alpha (INHA).<ref name=quadrate/> | |||
| |- | |||
| |AFP/free beta screen | |||
| |align="center"|13–22 | |||
| |align="center"|80% | |||
| |align="center"|2.8% | |||
| |This test measures the ], produced by the fetus, and free beta hCG, produced by the ]. | |||
| |- | |||
| |Nuchal translucency/free beta/PAPPA screen | |||
| |align="center"|10–13.5 | |||
| |align="center"|91%<ref name=nasalbone>Some practices report adding Nasal Bone measurements and increasing the detection rate to 95% with a 2% False Positive Rate.</ref> | |||
| |align="center"|5%<ref name=nasalbone>Some practices report adding Nasal Bone measurements and increasing the detection rate to 95% with a 2% False Positive Rate.</ref> | |||
| |Uses ] to measure ] in addition to the freeBeta ] and PAPPA (]). NIH has confirmed that this first trimester test is more accurate than second trimester screening methods.<ref>NIH FASTER study (NEJM 2005 ('''353'''):2001). See also J.L. Simplson's editorial (NEJM 2005 ('''353'''):19).</ref> | |||
| |} | |||
| ]]] | |||
| Even with the best non-invasive screens, the detection rate is 90%–95% and the rate of false positive is 2%–5%. ]s can be caused by undetected multiple fetuses (very rare with the ultrasound tests), incorrect date of pregnancy, or normal variation in the proteins. | |||
| Confirmation of screen positive is normally accomplished with ]. This is an invasive procedure and involves taking ] from the mother and identifying fetal cells. The lab work can take several weeks but will detect over 99.8% of all numerical chromosomal problems with a very low false positive rate. <!-- Although amniocentesis is very accurate, there are a significant number of pregnancies where the test is impossible to perform because of the position of the placenta. Please would someone add some statistics here!!! --><ref>{{cite web |title=Down syndrome |author=Fackler, A |url=http://health.yahoo.com/topic/children/baby/article/healthwise/hw167989 |accessdate = 2006-09-07}}</ref> | |||
| Due to the low incidence of Down syndrome, a vast majority of early screen positives are false.<ref>Assume the false positive rate is 2% (at the low end), the incidence of Down syndrome is 1/500 (on the high side) with 95% detection, and there is no ]. Out of 100,000 screens, 200 will have Down syndrome, and the screen will detect 190 of them. From the 99,800 normal pregnancies, 1996 will be given a positive result. So, among the 2,186 positive test results, 91% will be false positives and 9% will be true positives.</ref> Since false positives typically prompt an amniocentesis to confirm the result, and the amniocentesis carries a small risk of inducing ], there is a slight risk of miscarrying a healthy fetus. (The added miscarriage risk from an amniocentesis is traditionally quoted as 0.5%, but recent studies suggest that it may be considerably smaller (0.06% with a 95% CI of 0 to 0.5%).<ref>{{cite journal |title=Pregnancy loss rates after midtrimester amniocentesis |author=Eddleman, Keith A., ''et al'' |journal=Obstet Gynecol|year=2006|volume=108|issue=5|pages=1067–1072|url=http://www.greenjournal.org/cgi/content/short/108/5/1067 |accessdate = 2006-12-09}} PMID 17077226</ref>) | |||
| A 2002 literature review of elective abortion rates found that 91–93% of pregnancies with a diagnosis of Down syndrome were terminated.<ref>{{cite journal| author=Caroline Mansfield, Suellen Hopfer, Theresa M. Marteau| title=Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review| year=1999| journal=Prenatal Diagnosis| volume=19| issue=9| pages=808–812| url=http://www3.interscience.wiley.com/cgi-bin/abstract/65500197/ABSTRACT}} PMID 10521836 This is similar to 90% results found by {{cite journal| title=Determinants of parental decisions after the prenatal diagnosis of Down syndrome: Bringing in context| journal=American Journal of Medical Genetics| volume=93| issue=5| pages=410–416| year=1999| author=David W. Britt, Samantha T. Risinger, Virginia Miller, Mary K. Mans, Eric L. Krivchenia, Mark I. Evans}} PMID 10951466</ref> Physicians and ethicists are concerned about the ethical ramifications,<ref>{{cite journal| author=Glover, NM and Glover, SJ| title=Ethical and legal issues regarding selective abortion of fetuses with Down syndrome| journal=Ment. Retard.| year=1996| volume=34| issue=4| pages=207–214| id=PMID 8828339}}</ref> with some commentators calling it "] by abortion".<ref>{{cite journal |last=Will |first=George |title=Eugenics By Abortion: Is perfection an entitlement? |date=2005-04-14 |journal=Washington Post |pages=A37 |url=http://www.washingtonpost.com/wp-dyn/articles/A51671-2005Apr13.html |accessdate = 2006-07-03}}</ref> Many members of the ] movement "believe that public support for prenatal diagnosis and abortion based on disability contravenes the movement's basic philosophy and goals."<ref>{{cite journal |author=Erik Parens and Adrienne Asch |title=Disability rights critique of prenatal genetic testing: Reflections and recommendations |year=2003 |journal=Mental Retardation and Developmental Disabilities Research Reviews |volume=9 |issue=1 |page=40–47 |url=http://www3.interscience.wiley.com/cgi-bin/abstract/102531130/ABSTRACT| accessdate = 2006-07-03}} PMID 12587137</ref> | |||
| ==Cognitive development== | |||
| ] in children with Down syndrome is quite variable. It is not currently possible at birth to predict the capabilities of any individual reliably, nor are the number or appearance of physical features predictive of future ability. The identification of the best methods of teaching each particular child ideally begins soon after birth through early intervention programs.<ref>{{cite web|url=http://www.ndss.org/index.php?option=com_content&task=view&id=2015&Itemid=198|title=Dear New or Expectant Parents|publisher=National Down Syndrome Society|accessdate = 2006-05-12}} Also {{cite web |url=http://www.downsed.org/topics/early-intervention/ |title=Research projects - Early intervention and education |accessdate = 2006-06-02}}</ref> Since children with Down syndrome have a wide range of abilities, success at school can vary greatly, which stresses the importance of evaluating children individually. The cognitive problems that are found among children with Down syndrome can also be found among typical children. Therefore, parents can use general programs that are offered through the schools or other means. | |||
| Language skills show a difference between understanding speech and expressing speech. It is not uncommon for children with Down Syndrome to have a speech delay. Although it is common for them to need speech therapy to help with expressive language.<ref>{{cite journal| author =Bird, G. and S. Thomas| year =2002| title = Providing effective speech and language therapy for children with Down syndrome in mainstream settings: A case example | journal =Down Syndrome News and Update| volume =2| issue =1| pages =30–31}} Also, {{cite book| last =Kumin| first=Libby| editor=Hassold, T.J.and D. Patterson| title =Down Syndrome: A Promising Future, Together| year =1998| publisher =Wiley-Liss| location =New York| chapter = Comprehensive speech and language treatment for infants, toddlers, and children with Down syndrome}}</ref> ]s are delayed<ref>{{cite web| title=Development of Fine Motor Skills in Down Syndrome| url=http://www.about-down-syndrome.com/fine-motor-skills-in-down-syndrome.html| accessdate = 2006-07-03}}</ref> and often lag behind ]s and can interfere with cognitive development. Gross Motor Skills can be affected anywhere from minor to major. Some children will walk at around 2 while others around 4, it all depends. A physical therapist or APE will help a child with this. <ref>{{cite web |author = M. Bruni|url=http://www.ds-health.com/occther.htm| title=Occupational Therapy and the Child with Down Syndrome|accessdate = 2006-06-02}}</ref> | |||
| In education, ] of children with Down syndrome is becoming less controversial in many countries. For example, there is a presumption of mainstream in many parts of the UK. Mainstreaming is the process whereby students of differing abilities are placed in classes with their chronological peers. Children with Down syndrome may not age emotionally/socially and intellectually at the same rates as children without Down syndrome, so over time the intellectual and emotional gap between children with and without Down syndrome may widen. Complex thinking as required in sciences but also in history, the arts, and other subjects can often be beyond the abilities of some, or achieved much later than in other children. Therefore, children with Down syndrome may benefit from mainstreaming provided that some adjustments are made to the curriculum.<ref>{{cite web|author=S.E.Armstrong|url=http://www.altonweb.com/cs/downsyndrome/index.htm?page=ndssincl.html|title=Inclusion: Educating Students with Down Syndrome with Their Non-Disabled Peers|accessdate = 2006-05-12}} Also, see {{cite web|url=http://www.altonweb.com/cs/downsyndrome/index.htm?page=bosworth.html| title=Benefits to Students with Down Syndrome in the Inclusion Classroom: K-3| author=Debra L. Bosworth| accessdate = 2006-06-12}} Finally, see a survey by NDSS on inclusion, {{cite web|url=http://www.altonweb.com/cs/downsyndrome/index.htm?page=wolpert.html| title=The Educational Challenges Inclusion Study| author=Gloria Wolpert| year=1996| publisher=National Down Syndrome Society| accessdate = 2006-06-28}}</ref> | |||
| Some European countries such as ] and ] advise a two-teacher system, whereby the second teacher takes over a group of children with disabilities within the class. A popular alternative is cooperation between ]s and mainstream schools. In cooperation, the core subjects are taught in separate classes, which neither slows down the typical students nor neglects the students with disabilities. Social activities, outings, and many sports and arts activities are performed together, as are all breaks and meals.<ref>There are many such programs. One is described by Action Alliance for Children, {{web cite|author=K. Flores| url=http://www.4children.org/news/103spec.htm|title=Special needs, "mainstream" classroom|accessdate = 2006-05-13}} Also, see {{web cite|author=Flores, K.|url=http://www.4children.org/pdf/103spec.pdf|title=Special needs, "mainstream" classroom|accessdate = 2006-05-13}}</ref> | |||
| ==Health== | |||
| {{main|Health aspects of Down syndrome}} | |||
| The medical consequences of the extra genetic material in Down syndrome are highly variable and may affect the function of any organ system or bodily process. The health aspects of Down syndrome encompass anticipating and preventing effects of the condition, recognizing complications of the disorder, managing individual symptoms, and assisting the individual and his/her family in coping and thriving with any related disability or illnesses.<ref>{{cite journal| author=American Academy of Pediatrics Committee on Genetics| title=American Academy of Pediatrics: Health supervision for children with Down syndrome| journal=Pediatrics| year=2001| month=Feb| volume=107| issue=2| pages=442–449| id=PMID 11158488}}</ref> | |||
| The most common manifestations of Down syndrome are the characteristic facial features, cognitive impairment, ] (typically a ]), hearing deficits (maybe due to sensory-neural factors, or chronic serous otitis media, also known as Glue-ear), ], ] disorders, and ]. Other less common serious illnesses include ], ], and ]. However, health benefits of Down syndrome include greatly reduced incidence of many common malignancies except leukemia and testicular cancer<ref>Yang Q, Rasmussen SA, Friedman JM. ''Lancet'' 2002 ];359(9311):1019–25. PMID 11937181</ref> — although it is, as yet, unclear whether the reduced incidence of various fatal cancers among people with Down syndrome is as a direct result of tumor-suppressor genes on chromosome 21, because of reduced exposure to ]s that contribute to cancer risk, or some other as-yet unspecified factor. Down syndrome can result from several different genetic mechanisms. This results in a wide variability in individual symptoms due to complex gene and environment interactions. Prior to birth, it is not possible to predict the symptoms that an individual with Down syndrome will develop. Some problems are present at birth, such as certain heart malformations. Others become apparent over time, such as epilepsy. | |||
| These factors can contribute to a significantly shorter lifespan for people with Down syndrome. One study, carried out in the ] in 2002, showed an average lifespan of 49 years, with considerable variations between different ethnic and socio-economic groups.<ref name="lifespan">{{cite news |first = Emma | |||
| |last = Young | |||
| |authorlink = | |||
| |author = | |||
| |coauthors = | |||
| |title = Down's syndrome lifespan doubles | |||
| |url = http://www.newscientist.com/article.ns?id=dn2073 | |||
| |format = | |||
| |work = New Scientist | |||
| |publisher = | |||
| |pages = | |||
| |page = | |||
| |date = 2002-03-22 | |||
| |accessdate = 2006-10-14 | |||
| |language = }} | |||
| </ref> | |||
| Fertility amongst both males and females is reduced,<ref name="fertility">{{cite journal | |||
| | author = Ying-Hui H. Hsiang, Gary D. Berkovitz, Gail L. Bland, Claude J. Migeon, Andrew C. Warren, John M. Opitz, James F. Reynolds | |||
| | title = Gonadal function in patients with Down syndrome | |||
| | journal = American Journal of Medical Genetics | |||
| | volume = 27 | |||
| | issue = 2 | |||
| | pages = 449—458 | |||
| | publisher = Wiley-Liss, Inc. | |||
| | date = 1987 | |||
| | url = http://dx.doi.org/10.1002/ajmg.1320270223 | |||
| | id = 10.1002/ajmg.1320270223 | |||
| | format = | |||
| | accessdate = }}</ref> with only three recorded instances of males with Down syndrome fathering children.<ref>{{cite journal |author=Sheridan R, Llerena J, Matkins S, Debenham P, Cawood A, Bobrow M |title=Fertility in a male with trisomy 21 |journal=J Med Genet |volume=26 |issue=5 |pages=294-8 |year=1989 |pmid=2567354}}</ref><ref>{{cite journal |author=Pradhan M, Dalal A, Khan F, Agrawal S |title=Fertility in men with Down syndrome: a case report |journal=Fertil Steril |volume=86 |issue=6 |pages=1765.e1–3 |year=2006 |pmid=17094988}}</ref> | |||
| ==Genetic research== | |||
| {{main|Research of Down syndrome-related genes}} | |||
| Down syndrome is “a developmental abnormality characterized by ] of human ] (Nelson 619). The extra copy of chromosome-21 leads to an over expression of certain ] located on chromosome-21. | |||
| Research by Arron ''et al'' shows that some of the ] (displayed genetic characteristics), associated with Down Syndrome can be related to the dysregulation of gene-regulating proteins (596). The gene-regulating proteins bind to ] and initiate certain segments of DNA to be replicated for the production of a certain protein (Arron ''et al''. 596). The gene-regulator in interest is called NFATc. Its activities are controlled by two proteins, DSCR1 and DYRK1A; these genes are located on chromosome-21 (Epstein 582). In people with Down Syndrome, these proteins have 1.5 times greater concentration than normal (Arron ''et al''. 597). The elevated levels of DSCR1 and DYRK1A mean that most of the NFATc is located in the ] rather than in the ] promoting ] which will produce vital proteins (Epstein 583). | |||
| This dysregulation was discovered by testing in ] mice. The mice had segments of their chromosomes duplicated to simulate a human chromosme-21 trisomy (Arron ''et al''. 597). A common characteristic of Down Syndrome is poor muscle tone, so a test involving the grip strength of the mice showed that the genetically modified mice had a significantly weaker grip (Arron ''et al''. 596). The mice squeezed a probe with a paw; the modified mice displayed a .2 Newton (measurement of force) weaker grip (Arron ''et al''. 596). Down syndrome is also characterized by increased socialization. Both modified and unmodified mice were observed for social interaction. The modified mice showed as many as 25% more interactions per time period as the unmodified mice (Arron ''et al''. 596). | |||
| The genes that may be responsible for the phenotypes associated may be located proximal to 21q22.3. Testing by Olson et al, in transgenic mice show the duplicated genes presumed to cause the phenotypes are not enough to cause the exact features. While the mice had sections of multiple genes duplicated to approximate a human chormosme-21 triplication, they only showed slight craniofacial abnormalities (688-690). The transgenic mice were compared to mice that had no gene duplication by measuring distances on various points on their skeletal structure and comparing them to the normal mice (Olson ''et al''. 687). The exact characteristics of Down Syndrome were not observed, so more genes involved for Down Syndrome ] have to be located elsewhere. | |||
| Reeves ''et al'', using 250 clones of chromosme-21 and specific gene markers, were able to map the gene in mutated bacteria. The testing had 99.7% coverage of the gene with 99.9995% accuracy due to multiple redundancies in the mapping techniques. In the study 225 genes were identified (311-313). | |||
| The search for major genes that may be involved in Down syndrome symptoms is normally in the region 21q21–21q22.3. However, studies by Reeves ''et al''. show that 41% of the genes on chromosome-21 of have no functional purpose, and only 54% of functional genes have a known protein sequence. Functionality of genes was determined by a computer using ] prediction analysis (312). ] sequence was obtained by the same procedures of the chromosome-21 mapping. | |||
| Research has led to an understanding that two genes located on chromosome-21, that code for proteins that control gene regulators, DSCR1 and DYRK1A can be responsible for some of the phenotypes associated with Down Syndrome. DSCR1 and DYRK1A cannot be blamed outright for the symptoms; there are a lot of genes that have no known purpose. And further research is needed in order to treat Down Sydrome more effectively. | |||
| Recent use of ] ] to study specific genes in the Down syndrome critical region has yielded some results. ]<ref>{{OMIM|104760}}, gene ] at ]. Retrieved on ].</ref> is an ] A4 precursor protein. It is suspected to have a major role in cognitive difficulties.<ref>{{cite web |title=Down syndrome traced to one gene |publisher=''The Scientist'' |first=Chandra |last= Shekhar |url=http://www.the-scientist.com/news/display/23869/ |date=2006-07-06 |accessdate = 2006-07-11}}</ref> Another gene, ETS2<ref>{{OMIM|164740}}, located at ] . Retrieved on ].</ref> is Avian Erythroblastosis Virus E26 Oncogene Homolog 2. Researchers have "demonstrated that overexpression of ETS2 results in ]. Transgenic mice overexpressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome."<ref>{{cite web |author=OMIM, NIH |url=http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164740 |title=V-ETS Avian Erythroblastosis virus E26 Oncogene Homolog 2 |accessdate = 2006-06-29}}</ref> | |||
| ==Sociological and cultural aspects== | |||
| ] for people with Down syndrome point to various factors, such as special education and parental support groups to make life easier for parents. There are also strides being made in education, housing, and social settings to create environments which are accessible and supportive to people with Down syndrome. In most developed countries, since the early twentieth century many people with Down syndrome were housed in institutions or colonies and excluded from society. However, since the early 1960s parents and their organizations (such as ), educators and other professionals have generally advocated a policy of inclusion,<ref>{{cite book |title=Inclusion |publisher=National Down Syndrome Society |url=http://www.ndss.org/index.php?option=com_content&task=view&id=1941&Itemid=236 |accessdate = 2006-05-21}}</ref> bringing people with any form of mental or physical disability into general society as much as possible. In many countries, people with Down syndrome are educated in the normal school system; there are increasingly higher-quality opportunities to mix special education with regular education settings. | |||
| Despite this change, reduced abilities of people with Down syndrome can pose a challenge to parents and families. Although living with family is preferable to ], people with Down syndrome often encounter patronizing attitudes and discrimination in the wider community. | |||
| The first ] was held on ] ]. The day and month were chosen to correspond with 21 and trisomy respectively. It was proclaimed by ].<ref>{{cite web| url=http://www.worlddownsyndromeday.org|title=World Down Syndrome Day| accessdate = 2006-06-02}}</ref> In the United States, the National Down Syndrome Society observes Down Syndrome Month every October as "a forum for dispelling stereotypes, providing accurate information, and raising awareness of the potential of individuals with Down syndrome."<ref></ref> In ], Down Syndrome Awareness Day is held every October 20.<ref></ref> | |||
| ==History== | |||
| {{main|History of Down syndrome}} | |||
| English physician ] first characterized Down syndrome as a distinct form of mental retardation in 1862, and in a more widely published report in 1866 entitled "Observations on an ethnic classification of idiots".<ref>{{cite journal| author=Down, J.L.H.| year=1866| title=Observations on an ethnic classification of idiots| journal=Clinical Lecture Reports, London Hospital| volume=3| pages=259–262| url=http://www.neonatology.org/classics/down.html| accessdate = 2006-07-14}} For a history of the disorder, see {{cite book | title= John Langdon Down, 1828–1896 | author=OC Ward |publisher=Royal Society of Medicine Press | id=ISBN 1-85315-374-5|year = 1998}} or {{cite web| last=Conor| first=Ward |url =http://www.intellectualdisability.info/values/history_DS.htm| title =John Langdon Down and Down's syndrome (1828–1896)| accessdate = 2006-06-02}}</ref> Due to his perception that children with Down syndrome shared physical facial similarities (]s) with those of ], Down used terms such as ''mongolism'' and ''Mongolian idiocy''.<ref>{{cite journal|Author =Conor, W.O.| year =1999| title =John Langdon Down: The Man and the Message| journal =Down Syndrome Research and Practice| volume =6| issue =1| pages =19–24| accessdate = 2006-06-02}}</ref> Down wrote that mongolism represented "retrogression," the appearance of ] traits in the children of allegedly more advanced Caucasian parents. | |||
| By the 20<sup>th</sup> century, "Mongolian idiocy" had become the most recognizable form of mental retardation. Most individuals with Down syndrome were ], few of the associated medical problems were treated, and most died in infancy or early adult life. With the rise of the ] movement, 33 of the (then) 48 ]s and several countries began programs of involuntary sterilization of individuals with Down syndrome and comparable degrees of disability. The ultimate expression of this type of public policy was the ] ] program ], begun in 1940. Court challenges and public revulsion led to discontinuation or repeal of such programs during the decades after ]. | |||
| Until the middle of the 20th century, the cause of Down syndrome remained unknown. However, the presence in all races, the association with older maternal age, and the rarity of recurrence had been noticed. Standard medical texts assumed it was caused by a combination of inheritable factors which had not been identified. Other theories focused on injuries sustained during birth.<ref>{{cite book |author=Warkany, J. |title=Congenital Malformations |location=Chicago |publisher=Year Book Medical Publishers, Inc |date=1971 |pages=313–314 |id=ISBN 0-8151-9098-0}}</ref> | |||
| With the discovery of ] techniques in the 1950s, it became possible to identify abnormalities of chromosomal number or shape. In 1959, ] discovered that Down syndrome resulted from an extra chromosome.<ref>{{cite web |url=http://www.fondationlejeune.org/eng/Content/Fondation/professeurlj.asp |title=Jérôme Lejeune Foundation |accessdate = 2006-06-02}}</ref> The extra chromosome was subsequently labeled as the 21st, and the condition as ] ]. | |||
| In 1961, nineteen geneticists wrote to the editor of '']'' suggesting that ''Mongolian idiocy'' had "misleading connotations," had become "an embarrassing term," and should be changed.<ref>{{cite journal |first=Allen |last=Gordon |coauthors=C.E. Benda, J.A. Böök, C.O. Carter, C.E. Ford, E.H.Y. Chu, E. Hanhart, George Jervis, W. Langdon-Down, J. Lejeune, H. Nishimura, J. Oster, L.S. Penrose, P.E. Polani, Edith L. Potter, Curt Stern, R. Turpin, J. Warkany, and Herman Yannet |year=1961 |title=Mongolism (Correspondence) |journal=] |pages=775 |volume=1 |issue=7180}}</ref> ''The Lancet'' supported ''Down's Syndrome''. The ] (WHO) officially dropped references to ''mongolism'' in 1965 after a request by the Mongolian delegate.<ref>{{cite journal|last=Howard-Jones |first=Norman| date=1979 |title=On the diagnostic term "Down's disease"| journal=Medical History |volume=23 |issue=1 |pages=102–104 |id=PMID 153994}}</ref> However, almost 40 years later, the term ‘mongolism’ still appears in leading medical texts such as ''Review of Medical Physiology'', 22nd Edition, 2005, by ] and ''General and Systematic Pathology'', 4th Edition, 2004, edited by ]. | |||
| In 1975, the United States ] convened a conference to standardize the nomenclature of malformations. They recommended eliminating the possessive form: "The possessive use of an eponym should be discontinued, since the author neither had nor owned the disorder."<ref>A planning meeting was held on ] ], resulting in a letter to ''The Lancet''.{{cite journal |year=1974 |title=Classification and nomenclature of malformation (Discussion) |journal=] |pages=798 |volume=303 |issue=7861}} The conference was held ]-] ], and reported to ''The Lancet'' shortly afterward.{{cite journal |year=1975 |title=Classification and nomenclature of morphological defects (Discussion) |journal=] |pages=513 |volume=305 |issue=7905}}</ref> Although both the possessive and non-possessive forms are used in the general population, Down syndrome is the accepted term among professionals in the USA, ] and other countries; Down's syndrome is still used in the ] and other areas.<ref name=name>{{cite web |last=Leshin |first=Len| date=2003 |url=http://www.ds-health.com/name.htm |title=What's in a name |accessdate = 2006-05-12}}</ref> | |||
| ==Notable individuals== | |||
| <!--- Do not add individuals here unless they have an entry in Misplaced Pages and the entry specifically mentions Down syndrome, or you can cite another source for such a claim ---> | |||
| Notable people with Down syndrome include: | |||
| *] (German actor)<ref>http://www.bobby.de/</ref> | |||
| * ], actor ('']'') and autobiographer.<ref>{{cite web | |||
| | url = http://www.chrisburke.org/bio.php | |||
| | title = About Us | |||
| | accessdate = 2006-12-08 | |||
| | work = Chris Burke with Joe and John DeMasi | |||
| | publisher = Official Site | |||
| }}</ref> | |||
| * ], a Belgian actor who shared the prize for best lead actor with ] in Festival de Cannes in 1996 for his performance in the movie '']''. King Albert II of Belgium made him Commander in the Order of the Crown in 2004.<ref>{{cite web | |||
| | url = http://www.imdb.com/name/nm0243608/bio | |||
| | title = Pascal Duquenne | |||
| | accessdate = 2007-02-21 | |||
| | publisher = ].com | |||
| }}</ref> | |||
| * ] (1928–1948), daughter of ].<ref>{{cite web | |||
| | url = http://www.channel4.com/history/microsites/H/history/c-d/degaulle.html | |||
| | title = Charles de Gaulle | |||
| | accessdate = 2006-12-08 | |||
| | work = Channel 4 – History | |||
| | publisher = Channel4.com | |||
| | author = Jenny Vaughan | |||
| }}</ref> | |||
| * ], actor ('']'') — first actor with Down syndrome in the lead part of a motion picture.<ref>{{cite web | |||
| | url = http://www.stephane.ginnsz.com/ | |||
| | title = Film Actor with Down Syndrome | |||
| | accessdate = 2006-12-08 | |||
| | publisher = ginnsz.com | |||
| | author = Stephane Ginnsz | |||
| }}</ref> | |||
| * ], actor ('']'').<ref>; </ref> | |||
| * ], ] locker room attendant.<ref>{{cite news | |||
| | first = Chris | |||
| | last = Lomon | |||
| | title = NHL Alumni RBC All-Star Awards Dinner | |||
| | url = http://www.nhlalumni.com/slam/hockey/nhlalumni/news/03/0228.html | |||
| | publisher = NHL Alumni | |||
| | date = ] | |||
| | accessdate = 2006-12-08 | |||
| }}</ref> | |||
| * ], adopted daughter of ] first baseman ] and inspiration for the Pujols Family Foundation.<ref>{{cite web | |||
| | url = http://www.pujolsfamilyfoundation.org/index2.html | |||
| | title = Pujols Family Foundation Home Page | |||
| | accessdate = 2006-12-08 | |||
| }}</ref> | |||
| * ] Scottish film actress and Special Olympic athlete (netball). Her role in the 2003 film, ''Afterlife''<ref>{{cite web | |||
| | url = http://www.channel4.com/film/reviews/film.jsp?id=134586 | |||
| | title = AfterLife Movie Review (2003)from Channel 4 Film | |||
| | accessdate = 2007-04-21}}</ref> brought her a BAFTA award for best first time performance. ''Afterlife'' won the Audience Award at The Edinburgh Film Festival 2003. It also won Paula a role as Donna in BBC Scotland's River City. | |||
| * ], artist.<ref>{{cite web | |||
| | url = http://www.hidden-worlds.com/judithscott/entwined.htm | |||
| | title = Entwined - the life of Judith Scott | |||
| | accessdate = 2006-12-08 | |||
| | publisher = Judith Scott Foundation | |||
| | author = Joyce Scott | |||
| | date = ] | |||
| }}</ref> | |||
| * ], son of former ] head football coach ] and subject of the book ''Another Season: A Coach's Story of Raising an Exceptional Son.'' (ISBN 0767902556).<ref>Mason, Carolyn. ''The Tuscaloosa News'' (] ]). Retrieved ] ].</ref> | |||
| * ], singer with ]n avant-rock band ].<ref>{{cite web | |||
| | url = http://www.paristransatlantic.com/magazine/interviews/reynols.html | |||
| | title = Interview: Reynols | |||
| | accessdate = 2006-12-08 | |||
| | publisher = Judith Scott Foundation | |||
| | author = Dan Warburton | |||
| | date = ] | |||
| }}</ref> | |||
| * ] son of ] (retrospective speculation).<ref>{{cite journal | author = Steensma D | title = Down syndrome in Down House: trisomy 21, GATA1 mutations, and Charles Darwin | journal = Blood | volume = 105 | issue = 6 | pages = 2614–6 | year = 2005 | pmid = 15746086 | url = http://bloodjournal.hematologylibrary.org/cgi/content/full/105/6/2614-a}}</ref> | |||
| The Down Syndrome Association of Los Angeles maintains a list of individuals with Down syndrome in roles in TV and movies.<ref>Down Syndrome Association of Los Angeles. Retrieved ] ].</ref> | |||
| ==Portrayal in fiction== | |||
| * ]: '']'' | |||
| * ]: '']'' | |||
| * Paul M Belous & Robert Wolterstorff: '']: Jimmy'' | |||
| * ]: '']'' | |||
| * ] and its American counterpart, '']'' | |||
| * ]: '']'' | |||
| * ]: '']'' | |||
| * ]: '']'' | |||
| * ], character in '']'' | |||
| * ]: '']'' | |||
| * ]: '']'' | |||
| * ]: '']'' | |||
| * ]: '']'' | |||
| ==References == | |||
| {{reflist|2}} | |||
| *Arron, Joseph R., et al. (2006). NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. ''Nature, 441'': 595-599. | |||
| *Epstein, Charles J. (2006). Critical Genes in Critical Region. ''Nature, 441'': 582-583. | |||
| * {{cite book | |||
| | last =Ganong | |||
| | first =W.J. | |||
| | year =2005 | |||
| | title =Review of Medical Physiology | |||
| | publisher =Mc-Graw Hill | |||
| | location =New York | |||
| }} | |||
| *Nelson, David L., & Gibbs, Richard H. (2004). The Critical Region in Trisomy-21. ''Science, 306'': 619-621. | |||
| *Olson, L.E., Richtsmeier J.T., & Reeves R.H. (2004). A Chromosome-21 Critical Region Does Not Cause Specific Down Syndrome Phenotypes. ''Science, 306'': 687-690. | |||
| *Reeves, Roger H., et al. (2000). The DNA Sequence of Human Chromosome 21. ''Nature, 405'': 311-319. | |||
| * {{cite book | |||
| | last =Underwood | |||
| | first =J.C.E. | |||
| | year =2004 | |||
| | title =General and Systematic Pathology | |||
| | publisher =Churchill Livingstone | |||
| | location =Edinburgh | |||
| }} | |||
| ==Bibliography== | |||
| * {{cite book | |||
| | last =Beck | |||
| | first =M.N. | |||
| | year =1999 | |||
| | title =Expecting Adam | |||
| | publisher =Berkley Books | |||
| | location =New York | |||
| }} | |||
| * {{cite book | |||
| | last =Buckley | |||
| | first =S. | |||
| | year =2000 | |||
| | title =Living with Down Syndrome | |||
| | publisher =The Down Syndrome Educational Trust | |||
| | location =Portsmouth, UK | |||
| | url =http://books.google.com/books?id=__5wB08U2hMC | |||
| | isbn =1903806011 | |||
| }} | |||
| * {{cite book | |||
| | last =Down Syndrome Research Foundation | |||
| | year =2005 | |||
| | title =Bright Beginnings: A Guide for New Parents | |||
| | publisher =Down Syndrome Research Foundation | |||
| | location =Buckinghamshire, UK | |||
| | url =http://www.dsrf.co.uk/Reading_material/Bright_beginnings.htm | |||
| }} | |||
| * Hassold, T.J., D. Patterson, eds. (1999). ''Down Syndrome: A Promising Future, Together''. New York: Wiley Liss. | |||
| * {{cite book | |||
| | last =Kingsley | |||
| | first =J. | |||
| | coauthors =M. Levitz | |||
| | year =1994 | |||
| | title =Count Us In: Growing up with Down Syndrome | |||
| | publisher =Harcourt Brace | |||
| | location =San Diego | |||
| }} | |||
| * Pueschel, S.M., M. Sustrova, eds. (1997). ''Adolescents with Down Syndrome: Toward a More Fulfilling Life''. Baltimore, MD: Paul H. Brookes. | |||
| * {{cite book | |||
| | last =Selikowitz | |||
| | first =M. | |||
| | edition =2nd edition | |||
| | year =1997 | |||
| | title =Down Syndrome: The Facts | |||
| | publisher =Oxford University Press | |||
| | location =Oxford, UK | |||
| }} | |||
| * {{cite book | |||
| | last =Van Dyke | |||
| | first =D.C. | |||
| | coauthors =P.J. Mattheis, S. Schoon Eberly, J. Williams | |||
| | year =1995 | |||
| | title =Medical and Surgical Care for Children with Down Syndrome | |||
| | publisher =Woodbine House | |||
| | location =Bethesda, MD | |||
| }} | |||
| * {{cite book | |||
| | last =Zuckoff | |||
| | first =M. | |||
| | year =2002 | |||
| | title =Choosing Naia: A Family's Journey | |||
| | publisher =Beacon Press | |||
| | location =New York | |||
| }} | |||
| ==External links== | |||
| {{commonscat|Down syndrome}} | |||
| For comprehensive lists of Down syndrome links see | |||
| * | |||
| * | |||
| ===Societies and associations=== | |||
| <!-- This list is not for local support organizations, there are simply too many. Contact the lists in the previous subheading to make sure you are listed there, it is more appropriate. --> | |||
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| '''Health & Targeted Nutritional Intervention''' | |||
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| {{featured article}} | |||
| {{Chromosomal abnormalities}} | |||
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