View source for Down syndrome

{{Short description|Genetic disorder}}
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{{Infobox medical condition
| name          = Down syndrome
| image         = Boy with Down Syndrome.JPG <!-- Do not change this picture without discussing it in the Down syndrome discussion page. Because of continued vandalism, pictures will be immediately reverted. -->
| alt           = Eight year old boy with Down syndrome
| caption       = An eight-year-old boy displaying characteristic facial features of Down syndrome
| field         = [[Medical genetics]], [[pediatrics]]
| synonyms      = Down's syndrome, Down's, trisomy 21
| symptoms      = Delayed [[Child development|development]], characteristic physical features, mild to moderate [[intellectual disability]]<ref name=Wei2010/>
| complications = 
| onset         = Mostly at conception, rarely after [[fertilization]]<ref name=NIH2014Cause/>
| duration      = Lifelong
| causes        = Third copy of [[chromosome 21]]<ref name=Patt2009/>
| risks         = [[Advanced maternal age|Older age of mother]], prior affected child<ref name=Mor2002/><ref>{{cite web |title=Down syndrome – Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/down-syndrome/symptoms-causes/syc-20355977 |website	=Mayo Clinic |access-date=17 March 2019 |language=en}}</ref>
| diagnosis     = [[Prenatal screening]], [[genetic testing]]<ref name=NIH2014Diag/>
| differential  = 
| prevention    = 
| treatment     = Physical therapy, occupational therapy, speech therapy, educational support, supported work environment<ref name=Roi2003/><ref name=NADS/>
| medication    = 
| prognosis     = Life expectancy 50 to 60 years (developed world)<ref name=Malt2013/><ref name=Nelson2011/>
| frequency     = 5.4 million (0.1%)<ref name=Wei2010/><ref name=GBD2015Pre/>
| named after   = [[John Langdon Down]]
}}

<!-- Definition and symptoms -->
'''Down syndrome''' or '''Down's syndrome''',<ref name=Smith-2011/> also known as '''trisomy 21''', is a [[genetic disorder]] caused by the presence of all or part of a third copy of [[chromosome 21]].<ref name=Patt2009>{{cite journal | vauthors = Patterson D | title = Molecular genetic analysis of Down syndrome | journal = Human Genetics | volume = 126 | issue = 1 | pages = 195–214 | date = July 2009 | pmid = 19526251 | doi = 10.1007/s00439-009-0696-8 | s2cid = 10403507  |issn = 0340-6717}}</ref> It is usually associated with [[child development|developmental]] delays, mild to moderate [[intellectual disability]], and characteristic physical features.<ref name="Wei2010">{{cite journal | vauthors = Weijerman ME, de Winter JP | title = Clinical practice. The care of children with Down syndrome | journal = European Journal of Pediatrics | volume = 169 | issue = 12 | pages = 1445–1452 | date = December 2010 | pmid = 20632187 | pmc = 2962780 | doi = 10.1007/s00431-010-1253-0 }}</ref><ref>{{Cite web |title=What are common symptoms of Down syndrome? |url=https://www.nichd.nih.gov/health/topics/down/conditioninfo/symptoms |access-date=28 March 2023 |website=NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development|date=31 January 2017 }}</ref>

<!-- Cause and diagnosis -->
The parents of the affected individual are usually [[genetically]] normal.<ref name=Steph2010>{{cite book| vauthors = Hammer GD |chapter=Pathophysiology of Selected Genetic Diseases | veditors = McPhee SJ |title=Pathophysiology of disease: an introduction to clinical medicine|year=2010|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-162167-0|pages=Chapter 2|edition=6th}}</ref> The incidence of the syndrome increases with the age of the mother, from less than 0.1% for 20-year-old mothers to 3% for those of age 45.<ref name=Mor2002/> It is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability.<ref name="NIH2014Cause">{{cite web |date=2014-01-17 |title=What causes Down syndrome? |url=https://www.nichd.nih.gov/health/topics/down/conditioninfo/causes |url-status=live |archive-url=https://web.archive.org/web/20160105082310/https://www.nichd.nih.gov/health/topics/down/conditioninfo/pages/causes.aspx |archive-date=5 January 2016 |access-date=6 January 2016 |work=National Institute of Child Health and Human Development |publisher=U.S. National Institutes of Health}}</ref> Three different genetic forms have been identified. The most common, trisomy 21, involves an extra copy of chromosome 21 in all cells.<ref name="www.intellectualdisability.info">{{Cite web |title=The Genetics of Down's Syndrome |url=http://www.intellectualdisability.info/conditions-associated-with-intellectual-disability/articles/the-genetics-of-downs-syndrome |access-date=2023-04-01 |website=www.intellectualdisability.info |language=en}}</ref> The extra chromosome is provided at conception as the egg and sperm combine.<ref>{{Cite web | work = National Association for Down Syndrome | title = Facts About Down Syndrome |url=https://www.nads.org/resources/facts-about-down-syndrome/ |access-date=2023-04-01 |language=en-US}}</ref> [[Translocation Down syndrome]] involves attachment of extra chromosome 21 material.<ref name="CDC" /><ref name="NDDS-about">{{Cite web |title=About Down Syndrome {{!}} National Down Syndrome Society (NDSS) |url=https://ndss.org/about |access-date=2023-03-28 |website=ndss.org |language=en}}</ref> In 1–2% of cases, the additional chromosome is added in the embryo stage and only affects some of the cells in the body; this is known as [[Mosaic Down syndrome]].<ref>{{Cite web |title=LSUHSC School of Medicine |url=https://www.medschool.lsuhsc.edu/genetics/down_syndrome.aspx |access-date=2023-04-01 |website=www.medschool.lsuhsc.edu}}</ref><ref name="www.intellectualdisability.info" />  

Down syndrome can be identified during pregnancy by [[prenatal screening]], followed by diagnostic testing, or after birth by direct observation and [[genetic testing]].<ref name=NIH2014Diag>{{cite web|title=How do health care providers diagnose Down syndrome?|url=https://www.nichd.nih.gov/health/topics/down/conditioninfo/diagnosis|website=Eunice Kennedy Shriver National Institute of Child Health and Human Development|access-date=4 March 2016|date=2014-01-17|url-status=live|archive-url=https://web.archive.org/web/20160307142500/https://www.nichd.nih.gov/health/topics/down/conditioninfo/Pages/diagnosed.aspx|archive-date=7 March 2016}}</ref> Since the introduction of screening, Down syndrome [[pregnancies]] are often [[Abortion|aborted]] (rates varying from 50 to 85% depending on maternal age, gestational age, and maternal race/ethnicity).<ref>{{cite journal | vauthors = Seror V, L'Haridon O, Bussières L, Malan V, Fries N, Vekemans M, Salomon LJ, Ville Y | display-authors = 6 | title = Women's Attitudes Toward Invasive and Noninvasive Testing When Facing a High Risk of Fetal Down Syndrome | journal = JAMA Network Open | volume = 2 | issue = 3 | pages = e191062 | date = March 2019 | pmid = 30924894 | pmc = 6450316 | doi = 10.1001/jamanetworkopen.2019.1062 }}</ref><ref name=Nat2012>{{cite journal | vauthors = Natoli JL, Ackerman DL, McDermott S, Edwards JG | title = Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995-2011) | journal = Prenatal Diagnosis | volume = 32 | issue = 2 | pages = 142–153 | date = February 2012 | pmid = 22418958 | doi = 10.1002/pd.2910 | doi-access = free }}</ref><ref name=Mans1999>{{cite journal | vauthors = Mansfield C, Hopfer S, Marteau TM | title = Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review. European Concerted Action: DADA (Decision-making After the Diagnosis of a fetal Abnormality) | journal = Prenatal Diagnosis | volume = 19 | issue = 9 | pages = 808–812 | date = September 1999 | pmid = 10521836 | doi = 10.1002/(sici)1097-0223(199909)19:9<808::aid-pd637>3.0.co;2-b | publisher = Wiley | s2cid = 29637272 | url = https://escholarship.org/uc/item/1rj1h8q6 }}</ref>

<!-- Management and prognosis -->
There is no cure for Down syndrome.<ref>{{cite web|title=Down Syndrome: Other FAQs|url=https://www.nichd.nih.gov/health/topics/down/more_information/faqs|access-date=6 January 2016|date=2014-01-17|url-status=live|archive-url=https://web.archive.org/web/20160106221704/https://www.nichd.nih.gov/health/topics/down/conditioninfo/Pages/faqs.aspx|archive-date=6 January 2016}}</ref> Education and proper care have been shown to provide better [[quality of life]].<ref name=Roi2003>{{cite journal | vauthors = Roizen NJ, Patterson D | title = Down's syndrome | journal = Lancet | volume = 361 | issue = 9365 | pages = 1281–1289 | date = April 2003 | pmid = 12699967 | doi = 10.1016/S0140-6736(03)12987-X | type = Review | s2cid = 33257578 }}</ref> Some children with Down syndrome are educated in typical school classes, while others require more [[Special education|specialized education]].<ref name=NADS/> Some individuals with Down syndrome graduate from [[high school]], and a few attend [[post-secondary education]].<ref name=Stein2011>{{cite book| vauthors = Steinbock B | chapter = The Risk of Transmitting Disease or Disability |title=Life before birth the moral and legal status of embryos and fetuses |year=2011|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-971207-6|page=222| chapter-url = https://books.google.com/books?id=1ehYs43QBYAC&pg=PA222 |edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20170123082359/https://books.google.com/books?id=1ehYs43QBYAC&pg=PA222|archive-date=2017-01-23}}</ref> In adulthood, about 20% in the United States do some paid work,<ref name=US2013>{{cite news| vauthors = Szabo L |title=Life with Down syndrome is full of possibilities |url=https://www.usatoday.com/story/news/nation/2013/05/01/life-down-syndrome-improving/2054953/|access-date=7 February 2014|newspaper=USA Today|date=May 9, 2013|url-status=live|archive-url=https://web.archive.org/web/20140108012711/http://www.usatoday.com/story/news/nation/2013/05/01/life-down-syndrome-improving/2054953/|archive-date=8 January 2014}}</ref> with many requiring a [[sheltered workshop|sheltered work environment]].<ref name=NADS>{{cite web |title=Facts About Down Syndrome |publisher=National Association for Down Syndrome |url=http://www.nads.org/pages_new/facts.html |access-date=20 March 2012 |archive-url=https://web.archive.org/web/20120403162637/http://www.nads.org/pages_new/facts.html |archive-date=3 April 2012 }}</ref> [[Caregiver]] support in financial and legal matters is often needed.<ref name=Nelson2011/> Life expectancy is around 50 to 60&nbsp;years in the [[developed world]], with proper health care.<ref name=Malt2013/><ref name=Nelson2011>{{cite book| vauthors = Kliegma RM |title=Nelson textbook of pediatrics|year=2011|publisher=Saunders|location=Philadelphia|isbn=978-1-4377-0755-7|pages=Chapter 76.2|edition=19th|chapter=Down Syndrome and Other Abnormalities of Chromosome Number}}</ref> Regular [[Screening (medicine)|screening]] for health issues common in Down syndrome is recommended throughout the person's life.<ref name="Malt2013">{{cite journal | vauthors = Malt EA, Dahl RC, Haugsand TM, Ulvestad IH, Emilsen NM, Hansen B, Cardenas YE, Skøld RO, Thorsen AT, Davidsen EM | display-authors = 6 | title = Health and disease in adults with Down syndrome | journal = Tidsskrift for den Norske Laegeforening | volume = 133 | issue = 3 | pages = 290–294 | date = February 2013 | pmid = 23381164 | doi = 10.4045/tidsskr.12.0390 | doi-access = free }}</ref>

<!--Epidemiology and history -->
Down syndrome is the most common [[chromosomal abnormality]],<ref name="Martínez-Espinosa">{{cite journal | vauthors = Martínez-Espinosa RM, Molina Vila MD, Reig García-Galbis M | title = Evidences from Clinical Trials in Down Syndrome: Diet, Exercise and Body Composition | journal = International Journal of Environmental Research and Public Health | volume = 17 | issue = 12 | page = 4294 | date = June 2020 | pmid = 32560141 | pmc = 7344556 | doi = 10.3390/ijerph17124294 | doi-access = free }}</ref> occurring in about 1 in 1,000 babies born worldwide,<ref name=Wei2010/> and one in 700 in the US.<ref name="CDC"/> In 2015, there were 5.4 million people with Down syndrome globally, of whom 27,000 died, down from 43,000 deaths in 1990.<ref name=GBD2015Pre>{{cite journal | vauthors = ((GBD 2015 Disease and Injury Incidence and Prevalence Collaborators)) | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 }}</ref><ref name=GBD2015De>{{cite journal | vauthors = ((GBD 2015 Mortality and Causes of Death Collaborators)) | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 }}</ref><ref name="GDB2013">{{cite journal | vauthors = ((GBD 2013 Mortality and Causes of Death Collaborators)) | title = Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 | journal = Lancet | volume = 385 | issue = 9963 | pages = 117–171 | date = January 2015 | pmid = 25530442 | pmc = 4340604 | doi = 10.1016/S0140-6736(14)61682-2 }}</ref> The syndrome is named after British physician [[John Langdon Down]], who dedicated his medical practice to the cause.<ref name=Hick2012>{{cite journal | vauthors = Hickey F, Hickey E, Summar KL | title = Medical update for children with Down syndrome for the pediatrician and family practitioner | journal = Advances in Pediatrics | volume = 59 | issue = 1 | pages = 137–157 | year = 2012 | pmid = 22789577 | doi = 10.1016/j.yapd.2012.04.006 | publisher = Elsevier BV }}</ref> Some aspects were described earlier by French psychiatrist [[Jean-Étienne Dominique Esquirol]] in 1838 and French physician [[Édouard Séguin]] in 1844.<ref name=Evans2009p12>{{cite book| vauthors = Evans-Martin FF |title=Down syndrome|year=2009|publisher=Chelsea House|location=New York|isbn=978-1-4381-1950-2|page=[https://archive.org/details/downsyndrome0000evan/page/12 12]|url=https://archive.org/details/downsyndrome0000evan|url-access=registration}}</ref> The genetic cause was discovered in 1959.<ref name=Hick2012/>
{{TOC limit|3}}

==Signs and symptoms==
[[File:Autism somali Center 01.jpg|upright=1.2|thumb|A boy from Somalia with Down syndrome]]
Those with Down syndrome nearly always have physical and intellectual disabilities.<ref>{{cite book | veditors = Faragher R, Clarke B | chapter = Introduction | title=Educating Learners with Down Syndrome: Research, theory, and practice with children and adolescents | publisher=Taylor & Francis | year=2013 | isbn=978-1-134-67335-3 | chapter-url=https://books.google.com/books?id=0Y20AQAAQBAJ&pg=PA5 | page=5 | url-status=live | archive-url=https://web.archive.org/web/20170123082416/https://books.google.com/books?id=0Y20AQAAQBAJ&lpg=PR11&pg=PA5 | archive-date=2017-01-23}}</ref> As adults, their mental abilities are typically similar to those of an 8- or 9-year-old.<ref name=Malt2013/> At the same time, their emotional and social awareness is very high.<ref>{{cite journal | vauthors = Hippolyte L, Iglesias K, Van der Linden M, Barisnikov K | title = Social reasoning skills in adults with Down syndrome: the role of language, executive functions and socio-emotional behaviour | journal = Journal of Intellectual Disability Research | volume = 54 | issue = 8 | pages = 714–726 | date = August 2010 | pmid = 20590998 | doi = 10.1111/j.1365-2788.2010.01299.x }}</ref> They can have [[immunodeficiency|poor immune function]]<ref name=Steph2010/> and generally reach [[developmental milestones]] at a later age.<ref name=Nelson2011/> They have an increased risk of a number of health concerns, such as [[congenital heart defect]], [[epilepsy]], [[leukemia]], and [[thyroid disease]]s.<ref name=Hick2012/>
[[File:Malvernphoto b.jpg|thumb|Male adult with Down Syndrome pictured centre in the photo]]
{| class="wikitable"
|-
!Characteristics
!Percentage
!Characteristics
!Percentage
|-
|Mental impairment
| 99%<ref>{{cite book | vauthors = Johnston JM, Smyth MD, McKinstry RC | chapter = Basics of Neuroimaging in Pediatric Epilepsy | veditors = Pellock JM, Bourgeois BF, Dodson WE, Nordli Jr DR, Sankar R |title=Pediatric epilepsy diagnosis and therapy|year=2008|publisher=Demos Medical Pub.|location=New York|isbn=978-1-934559-86-4|page=Chapter 67| chapter-url=https://books.google.com/books?id=47fckyBY2XwC&pg=PA216-IA51|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20170123082424/https://books.google.com/books?id=47fckyBY2XwC&pg=PA216-IA51|archive-date=2017-01-23}}</ref>
|Abnormal teeth
| 60%<ref name=Eps2007>{{cite book| vauthors = Epstein CJ |title=The consequences of chromosome imbalance: principles, mechanisms, and models |year=2007 |publisher=Cambridge University Press |location=Cambridge |isbn=978-0-521-03809-6 |pages=255–256 |url=https://books.google.com/books?id=6SzKSM1t9MYC&pg=PA255 |url-status=live|archive-url=https://web.archive.org/web/20170123082736/https://books.google.com/books?id=6SzKSM1t9MYC&pg=PA255|archive-date=2017-01-23}}</ref>
|-
|Stunted growth
| 90%<ref>{{cite book | vauthors = Marion RW, Samanich JN | chapter = Genetics |title=Pediatrics for medical students|year=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-7030-9|page=259| chapter-url = https://books.google.com/books?id=z0ohenkQrY0C&pg=PA259 | veditors = Bernstein D, Shelov SP |edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20170123082701/https://books.google.com/books?id=z0ohenkQrY0C&pg=PA259|archive-date=2017-01-23}}</ref>
|[[Epicanthic fold|Slanted eyes]]
| 60%<ref name=Steph2010/>
|-
|[[Umbilical hernia]]
| 90%<ref>{{cite book| vauthors = Bertoti DB, Smith DE | chapter = Mental Retardation: Focus on Down Syndrome | veditors = Tecklin JS |title=Pediatric physical therapy|year=2008|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-5399-9|page=380| chapter-url = https://books.google.com/books?id=YX8pztQHX0MC&pg=PA380|edition=4th|url-status=live|archive-url=https://web.archive.org/web/20170123082243/https://books.google.com/books?id=YX8pztQHX0MC&pg=PA380|archive-date=2017-01-23}}</ref>
|Shortened hands
| 60%<ref name=Eps2007/>
|-
| Increased skin on back of neck
| 80%<ref name=Hick2012/>
|Short neck
| 60%<ref name=Eps2007/>
|-
|[[Hypotonia|Low muscle tone]]
| 80%<ref name=Dom2007>{{cite book| veditors = Domino FJ |title=The 5-minute clinical consult 2007|year=2007|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-6334-9|page=392|url=https://books.google.com/books?id=WSUMZ5ECEbMC&pg=PA392|edition=2007|url-status=live|archive-url=https://web.archive.org/web/20170123082614/https://books.google.com/books?id=WSUMZ5ECEbMC&pg=PA392|archive-date=2017-01-23}}</ref>
|[[Obstructive sleep apnea]]
| 60%<ref name=Hick2012/>
|-
|Narrow [[palate|roof of mouth]]
| 76%<ref name=Eps2007/>
|[[Clinodactyly|Bent fifth finger tip]]
| 57%<ref name=Steph2010/>
|-
|[[Brachycephaly|Flat head]]
| 75%<ref name=Steph2010/>
|[[Brushfield spots]] in the [[iris (anatomy)|iris]]
| 56%<ref name=Steph2010/>
|-
|Flexible ligaments
| 75%<ref name=Steph2010/>
|[[Single transverse palmar crease]]
| 53%<ref name=Steph2010/>
|-
|[[Macroglossia|Proportionally large tongue]]<ref name=Perk2009>{{cite journal | vauthors = Perkins JA | title = Overview of macroglossia and its treatment | journal = Current Opinion in Otolaryngology & Head and Neck Surgery | volume = 17 | issue = 6 | pages = 460–465 | date = December 2009 | pmid = 19713845 | doi = 10.1097/moo.0b013e3283317f89 | s2cid = 45941755 }}</ref>
| 75%<ref name=Dom2007/>
|Protruding tongue
| 47%<ref name=Eps2007/>
|-
|Abnormal [[pinna (anatomy)|outer ears]]
| 70%<ref name=Hick2012/>
|[[Congenital heart disease]]
| 40%<ref name=Eps2007/>
|-
|Flattened nose
| 68%<ref name=Steph2010/>
|[[Strabismus]]
| ≈35%<ref name=Wei2010/>
|-
|Separation of first and second toes
| 68%<ref name=Eps2007/>
|[[Undescended testicles]]
| 20%<ref>{{cite book| vauthors = Wilson GN, Cooley WC |title=Preventive management of children with congenital anomalies and syndromes.|year=2006|publisher=Cambridge University Press|location=Cambridge|isbn=978-0-521-61734-5|page=190|url=https://books.google.com/books?id=k0AHKmax9gwC&pg=PA190|edition=2nd | url-status=live|archive-url=https://web.archive.org/web/20170123082838/https://books.google.com/books?id=k0AHKmax9gwC&pg=PA190|archive-date=2017-01-23}}</ref>
|}

===Physical===
[[File:Feet of a boy with Down Syndrome.JPG|thumb|upright=1.4|Feet of a boy with Down syndrome, showing the deviated first toes]]
People with Down syndrome may have these physical characteristics: a [[microgenia|small chin]], [[epicanthic fold]]s, [[Hypotonia|low muscle tone]], a flat [[nasal bridge]], and a protruding tongue. A protruding tongue is caused by low tone and weak facial muscles, and often corrected with myofunctional exercises.<ref>{{Cite book | vauthors = Kumin L |title=Resource Guide to Oral Motor Skill Difficulties in Children with Down Syndrome |publisher=Loyola College of Maryland |location= | url = https://www.ndsccenter.org/wp-content/uploads/OralMotor.pdf }}</ref> Some characteristic airway features can lead to [[obstructive sleep apnea]] in around half of those with Down syndrome.<ref name=Hick2012/> Other common features include: excessive joint flexibility, extra space between [[Hallux|big toe]] and second toe, a [[Single transverse palmar crease|single crease of the palm]],  and short fingers.<ref name=Eps2007/><ref name=Dom2007/>

Instability of the [[atlantoaxial joint]] occurs in about 1–2%.<ref>{{cite journal | vauthors = Bull MJ, Trotter T, Santoro SL, Christensen C, Grout RW, Burke LW, Berry SA, Geleske TA, Holm I, Hopkin RJ, Introne WJ, Lyons MJ, Monteil DC, Scheuerle A, Stoler JM, Vergano SA, Chen E, Hamid R, Downs SM, Grout RW, Cunniff C, Parisi MA, Ralston SJ, Scott JA, Shapira SK, Spire P | display-authors = 6 | collaboration = Council on Genetics | title = Health Supervision for Children and Adolescents With Down Syndrome | journal = Pediatrics | volume = 149 | issue = 5 | date = May 2022 | article-number = e2022057010 | doi = 10.1542/peds.2022-057010 | pmid = 35490285 | s2cid = 248252638 | url = https://publications.aap.org/pediatrics/article/149/5/e2022057010/186778/Health-Supervision-for-Children-and-Adolescents?autologincheck=redirected | url-access = subscription }}</ref> Atlantoaxial instability may cause [[myelopathy]] due to cervical spinal cord compression later in life, this often manifests as new onset weakness, [[ataxia|problems with coordination]], bowel or bladder incontinence, and gait dysfunction.<ref name="Bull 2020">{{cite journal | vauthors = Bull MJ | title = Down Syndrome | journal = The New England Journal of Medicine | volume = 382 | issue = 24 | pages = 2344–2352 | date = June 2020 | pmid = 32521135 | doi = 10.1056/NEJMra1706537 | s2cid = 219586275 }}</ref> Serial imaging cannot reliably predict future cervical cord compression, but changes can be seen on neurological exam. The condition is surgically corrected with spine surgery.<ref name="Bull 2020" />

Growth in height is slower, resulting in adults who tend to have [[short stature]]—the average height for men is {{convert|154|cm|ftin|abbr=off}}, and for women is {{convert|142|cm|ftin|abbr=off}}.<ref>{{cite book|title=Williams Textbook of Endocrinology Expert Consult|year=2011|publisher=Elsevier Health Sciences|location=London|isbn=978-1-4377-3600-7|url=https://books.google.com/books?id=nbg1QOAObicC&pg=PT4756|edition=12th|url-status=live|archive-url=https://web.archive.org/web/20170123082306/https://books.google.com/books?id=nbg1QOAObicC&pg=PT4756|archive-date=2017-01-23}}</ref> Individuals with Down syndrome are at increased risk for [[obesity]] as they age due to hypothyroidism, other medical issues and lifestyle.<ref name=Hick2012/><ref>{{cite journal | vauthors = Pierce M, Ramsey K, Pinter J | title = Trends in Obesity and Overweight in Oregon Children With Down Syndrome | journal = Global Pediatric Health | volume = 6 | article-number = 2333794X19835640 | date = 2 April 2019 | pmid = 31044152 | pmc = 6446252 | doi = 10.1177/2333794X19835640 }}</ref> [[Growth chart]]s have been developed specifically for children with Down syndrome.<ref name=Hick2012/>

===Neurological===
[[File:A boy with Down syndrome using cordless drill to assemble a book case.jpg|upright=1.2|thumb|A boy with Down syndrome using a cordless drill to assemble a book case]]
This syndrome causes about a third of cases of intellectual disability.<ref name=Steph2010/> Many developmental milestones are delayed with the ability to crawl typically occurring around 8–22 months rather than 6–12 months, and the ability to walk independently typically occurring around 1–4 years rather than 9–18 months.<ref>{{Cite web |title=Early Development for Children with Down Syndrome |url=https://www.cambscommunityservices.nhs.uk/Bedfordshire/services/occupational-therapy/ot-leaflets/down-syndrome |access-date=28 March 2023 |website=INHS Cambridgeshire Community Services NHS Trust}}</ref> Walking is acquired in 50% of children after 24 months.<ref>{{cite journal | vauthors = Winders P, Wolter-Warmerdam K, Hickey F | title = A schedule of gross motor development for children with Down syndrome | journal = Journal of Intellectual Disability Research | volume = 63 | issue = 4 | pages = 346–356 | date = April 2019 | pmid = 30575169 | doi = 10.1111/jir.12580 | s2cid = 58592265 }}</ref>

Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) [[intellectual disability]] with some cases having severe (IQ: 20–35) difficulties.<ref name=Wei2010/><ref name=Reil2012>{{cite journal | vauthors = Reilly C | title = Behavioural phenotypes and special educational needs: is aetiology important in the classroom? | journal = Journal of Intellectual Disability Research | volume = 56 | issue = 10 | pages = 929–946 | date = October 2012 | pmid = 22471356 | doi = 10.1111/j.1365-2788.2012.01542.x | doi-access = free }}</ref> Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that.<ref>{{cite book|title=Children with disabilities|year=2005|publisher=Paul H. Brookes|location=Baltimore [u.a.]|isbn=978-1-55766-581-2|page=308|url=https://books.google.com/books?id=P65sAAAAMAAJ&q=IQ+%22mosaic+down+syndrome%22|edition=5th| veditors = Batshaw M |url-status=live|archive-url=https://web.archive.org/web/20170123082658/https://books.google.com/books?id=P65sAAAAMAAJ&q=IQ+%22mosaic+down+syndrome%22|archive-date=2017-01-23}}</ref> As they age, the gap tends to widen between people with Down syndrome and their same-age peers.<ref name=Reil2012/><ref>{{cite journal | vauthors = Patterson T, Rapsey CM, Glue P | title = Systematic review of cognitive development across childhood in Down syndrome: implications for treatment interventions | journal = Journal of Intellectual Disability Research | volume = 57 | issue = 4 | pages = 306–318 | date = April 2013 | pmid = 23506141 | doi = 10.1111/j.1365-2788.2012.01536.x }}</ref>

Commonly, individuals with Down syndrome have better language understanding than ability to speak.<ref name=Hick2012/><ref name=Reil2012/> [[Babbling]] typically emerges around 15 months on average.<ref>{{cite journal | vauthors = Windsperger K, Hoehl S | title = Development of Down Syndrome Research Over the Last Decades-What Healthcare and Education Professionals Need to Know | journal = Frontiers in Psychiatry | volume = 12 | article-number = 749046 | date = 2021 | pmid = 34970162 | pmc = 8712441 | doi = 10.3389/fpsyt.2021.749046 | doi-access = free }}</ref> 10–45% of those with Down syndrome have either a [[stutter]] or [[cluttering|rapid and irregular speech]], making it difficult to understand them.<ref>{{cite journal | vauthors = Kent RD, Vorperian HK | title = Speech impairment in Down syndrome: a review | journal = Journal of Speech, Language, and Hearing Research | volume = 56 | issue = 1 | pages = 178–210 | date = February 2013 | pmid = 23275397 | pmc = 3584188 | doi = 10.1044/1092-4388(2012/12-0148) }}</ref> After reaching 30&nbsp;years of age, some may lose their ability to speak.<ref name=Malt2013/>

They typically do fairly well with social skills.<ref name=Hick2012/> Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability.<ref name=Reil2012/> In children with Down syndrome, [[mental illness]] occurs in nearly 30% with [[autism spectrum|autism]] occurring in 5–10%.<ref name=Nelson2011/> People with Down syndrome experience a wide range of emotions.<ref>{{cite book| vauthors = McGuire D, Chicoine B |title=Mental Wellness in Adults with Down Syndrome|year=2006|publisher=Woodbine House, Inc.|location=Bethesday, MD|isbn=978-1-890627-65-2|page=49}}</ref> While people with Down syndrome are generally happy,<ref>{{cite book| vauthors = Margulies P |title=Down syndrome|year=2007|publisher=Rosen Pub. Group|location=New York|isbn=978-1-4042-0695-3|page=[https://archive.org/details/downsyndrome0000marg/page/5 5]|url=https://archive.org/details/downsyndrome0000marg|url-access=registration|edition=1st}}</ref> symptoms of [[Depression (mood)|depression]] and [[anxiety (mood)|anxiety]] may develop in early adulthood.<ref name=Malt2013/>

Children and adults with Down syndrome are at increased risk of [[epileptic seizures]], which occur in 5–10% of children and up to 50% of adults.<ref name=Malt2013/> This includes an increased risk of a specific type of seizure called [[infantile spasms]].<ref name=Hick2012/> Many (15%) who live 40 years or longer develop [[Alzheimer's disease]].<ref>{{cite book|title=The 5-minute pediatric consult|year=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1-4511-1656-4|page=289|url=https://books.google.com/books?id=v7pbSFfMHCoC&pg=PA289|edition=6th | veditors = Schwartz MW |url-status=live|archive-url= https://web.archive.org/web/20170123083059/https://books.google.com/books?id=v7pbSFfMHCoC&pg=PA289|archive-date=2017-01-23}}</ref> In those who reach 60&nbsp;years of age, 50–70% have the disease.<ref name="Malt2013"/>

[[Down syndrome regression disorder]] is a sudden [[Regression (medicine)|regression]] with [[neuropsychiatric]] symptoms such as [[catatonia]], possibly caused by an autoimmune disease.<ref>{{Cite journal |last1=Santoro |first1=Jonathan D. |last2=Filipink |first2=Robyn A. |last3=Baumer |first3=Nicole T. |last4=Bulova |first4=Peter D. |last5=Handen |first5=Benjamin L. |date=2023-03-01 |title=Down syndrome regression disorder: updates and therapeutic advances |journal=Current Opinion in Psychiatry |volume=36 |issue=2 |pages=96–103 |doi=10.1097/YCO.0000000000000845 |issn=1473-6578 |pmid=36705008}}</ref>  It primarily appears in teenagers and younger adults.<ref>{{Cite book |last1=Skoto |first1=Brian G. |chapter-url=https://books.google.com/books?id=KYUCEQAAQBAJ&dq=%22Down+syndrome+regression+disorder%22&pg=PT1514 |title=The 5-Minute Clinical Consult 2025 |last2=Roberts |first2=Michele |date=2024-02-28 |publisher=Lippincott Williams & Wilkins |isbn=978-1-9752-3473-7 |editor-last=Domino |editor-first=Frank J. |language=en |chapter=Down Syndrome}}</ref>

===Senses===
[[File:Brushfield eye crop.jpg|thumb|upright=1.5|[[Brushfield spots]], visible in the irises of a baby with Down syndrome]]
Hearing and vision disorders occur in more than half of people with Down syndrome.<ref name=Hick2012/> 
<!-- Vision -->

==== Ocular findings ====
[[Brushfield spots]] (small white or grayish/brown spots on the periphery of the [[Iris (anatomy)|iris]]), upward slanting [[palpebral fissure]]s (the opening between the upper and lower lids) and [[Epicanthic folds|epicanthal folds]] (folds of skin between the upper eyelid and the nose) are clinical signs at birth suggesting the diagnosis of Down syndrome<ref name="Wei20102">{{cite journal |vauthors=Weijerman ME, de Winter JP |date=December 2010 |title=Clinical practice. The care of children with Down syndrome |journal=European Journal of Pediatrics |volume=169 |issue=12 |pages=1445–1452 |doi=10.1007/s00431-010-1253-0 |pmc=2962780 |pmid=20632187}}</ref><ref name="eyewiki.org">{{Cite web |title=Trisomy 21/Down Syndrome - EyeWiki |url=https://eyewiki.org/Trisomy_21/Down_Syndrome#Diagnosis |access-date=2024-05-07 |website=eyewiki.org |language=en}}</ref> especially in the [[Western world|Western World]].<ref name="eyewiki.org"/>  None of these requires treatment.{{Citation needed|date=May 2024}}

Visually significant congenital [[cataract]]s (clouding of the [[Lens (vertebrate anatomy)|lens]] of the eye) occur more frequently with Down syndrome.<ref name="eyewiki.org"/> [[Infant|Neonates]] with Down syndrome should be screened for cataract because early recognition and referral reduce the risk of vision loss from [[amblyopia]].<ref name="Bull-2022">{{Cite journal |last1=Bull |first1=Marilyn J. |last2=Trotter |first2=Tracy |last3=Santoro |first3=Stephanie L. |last4=Christensen |first4=Celanie |last5=Grout |first5=Randall W. |last6=THE COUNCIL ON GENETICS |date=2022-05-01 |title=Health Supervision for Children and Adolescents With Down Syndrome |url=https://publications.aap.org/pediatrics/article/149/5/e2022057010/186778/Health-Supervision-for-Children-and-Adolescents |journal=Pediatrics |language=en |volume=149 |issue=5 |article-number=e2022057010 |doi=10.1542/peds.2022-057010 |pmid=35490285 |issn=0031-4005|url-access=subscription }}</ref>  Dot-like opacities in the cortex of the [[Lens (anatomy)|lens]] (cerulean cataract) are present in up to 50% of people with Down syndrome, but may be followed without treatment if they are not visually significant.<ref name="eyewiki.org"/>

[[Strabismus]], [[nystagmus]] and [[nasolacrimal duct obstruction]] occur more frequently in children with Down syndrome.<ref name="eyewiki.org"/>  Screening for these diagnoses should begin within six months of birth.<ref name="eyewiki.org"/><ref name="Bull-2022" />  Strabismus is more often acquired than [[congenital]].<ref name="eyewiki.org"/>  Early diagnosis and treatment of strabismus reduces the risk of vision loss from amblyopia.<ref>{{Cite web |title=Strabismus and Amblyopia {{!}} Boston Children's Hospital |url=https://www.childrenshospital.org/conditions/strabismus-and-amblyopia#:~:text=Early%20diagnosis%20is%20essential%20in,the%20eyes%20are%20not%20aligned. |access-date=2024-05-08 |website=www.childrenshospital.org}}</ref>  In Down syndrome, the presence of epicanthal folds may give the false impression of [[strabismus]], referred to as [[pseudostrabismus]]. Nasolacrimal duct obstruction, which causes tearing ([[Epiphora (medicine)|epiphora]]), is more frequently bilateral and multifactorial than in children without Down syndrome.<ref name="eyewiki.org"/>

[[Refractive error]] is more common with Down syndrome, though the rate may not differ until after twelve months of age compared to children without Down syndrome.<ref name="eyewiki.org"/> Early screening is recommended to identify and treat significant refractive error with glasses or contact lenses. Poor [[Accommodation reflex|accommodation]] (ability to focus on close objects) is associated with Down syndrome, which may mean bifocals are indicated.<ref name="eyewiki.org"/>

In [[keratoconus]], the [[cornea]] progressively thins and bulges into a cone shape,<ref name="MayoClinic">{{Cite web |title=Keratoconus - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/keratoconus/symptoms-causes/syc-20351352 |access-date=2024-05-08 |website=Mayo Clinic |language=en}}</ref> causing visual blurring or distortion. Keratoconus first presents in the teen years and progresses into the thirties.<ref name="MayoClinic" /><ref name="hopkinsmedicine.org-2021">{{Cite web |date=2021-08-08 |title=Keratoconus |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/keratoconus |access-date=2024-05-08 |website=www.hopkinsmedicine.org |language=en}}</ref> Down syndrome is a strong risk factor for developing keratoconus, and onset may be occur at a younger age than in those without Down syndrome.<ref name="eyewiki.org"/>  Eye rubbing is also a risk factor for developing keratoconus.<ref name="hopkinsmedicine.org-2021" />  It is speculated that chronic eye irritation from [[blepharitis]] may increase eye rubbing in Down syndrome,<ref name="eyewiki.org"/> contributing to the increased prevalence of keratoconus.

An association between [[glaucoma]] and Down syndrome is often cited.<ref name="Wei20102"/>  Glaucoma in children with Down syndrome is uncommon, with a prevalence of less than 1%.<ref name="Wei20102"/><ref name="eyewiki.org"/>  It is currently unclear if the prevalence of glaucoma in those with Down syndrome differs from that in the absence of Down syndrome.<ref name="eyewiki.org"/>

Estimates of [[prevalence]] of ocular findings in Down Syndrome vary widely depending on the study.<ref name="eyewiki.org"/>  Some prevalence estimates follow. Vision problems have been observed in 38–80% of cases.<ref name="Wei20102"/> [[Brushfield spots]] are present in 38–85% of individuals.<ref name="Wei20102" />  Between 20 and 50% have [[strabismus]].<ref name="Wei20102" /> [[Cataract]]s occur in 15%,<ref name="Nelson20112">{{cite book |title=Nelson textbook of pediatrics |vauthors=Kliegma RM |publisher=Saunders |year=2011 |isbn=978-1-4377-0755-7 |edition=19th |location=Philadelphia |pages=Chapter 76.2 |chapter=Down Syndrome and Other Abnormalities of Chromosome Number}}</ref> and may be present at birth.<ref name="Wei20102" /> [[Keratoconus]] may occur in as many as 21–30%.<ref name="eyewiki.org" />

==== <!-- Hearing -->Hearing loss ====
Hearing problems are found in 50–90% of children with Down syndrome.<ref name=Rod2012/> This is often the result of [[otitis media with effusion]] which occurs in 50–70%<ref name=Nelson2011/> and chronic [[otitis media|ear infections]] which occur in 40–60%.<ref>{{cite book| vauthors = Evans-Martin FF |title=Down syndrome|year=2009|publisher=Chelsea House|location=New York|isbn=978-1-4381-1950-2|page=[https://archive.org/details/downsyndrome0000evan/page/71 71]|url=https://archive.org/details/downsyndrome0000evan|url-access=registration}}</ref> Ear infections often begin in the first year of life and are partly due to poor [[eustachian tube]] function.<ref name=Tint2010/><ref name=Sam2011>{{cite book|title=Handbook of neurodevelopmental and genetic disorders in children|year=2011|publisher=Guilford Press|location=New York|isbn=978-1-60623-990-2|page=365|url=https://books.google.com/books?id=Mm81tZFxf9UC&pg=PA365|edition=2nd| veditors = Goldstein S |url-status=live|archive-url=https://web.archive.org/web/20170123082556/https://books.google.com/books?id=Mm81tZFxf9UC&pg=PA365|archive-date=2017-01-23}}</ref> Excessive [[Earwax|ear wax]] can also cause hearing loss due to obstruction of the outer [[ear canal]].<ref name=Malt2013/> Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics.<ref name=Wei2010/><ref name=Sam2011/> It is important to rule out hearing loss as a factor in social and cognitive deterioration.<ref>{{cite book| vauthors = Prasher VP |title=Neuropsychological assessments of dementia in Down syndrome and intellectual disabilities |year=2009 |publisher=Springer |location=London |isbn=978-1-84800-249-4 |page=56 |url= https://books.google.com/books?id=RBQKsxodntgC&pg=PA56 |url-status=live |archive-url= https://web.archive.org/web/20170123082925/https://books.google.com/books?id=RBQKsxodntgC&pg=PA56|archive-date=2017-01-23}}</ref> Age-related hearing loss of the [[Sensorineural hearing loss|sensorineural type]] occurs at a much earlier age and affects 10–70% of people with Down syndrome.<ref name=Malt2013/>

===Heart===
The rate of [[congenital heart disease]] in newborns with Down syndrome is around 40%.<ref name=Eps2007/> Of those with heart disease, about 80% have an [[atrial septal defect]] or [[ventricular septal defect]] with the former being more common.<ref name=Malt2013/> Congenital heart disease can also put individuals at a higher risk of [[pulmonary hypertension]], where arteries in the lungs narrow and cause inadequate blood oxygenation.<ref name="Bush-2021">{{cite journal | vauthors = Bush D, Galambos C, Dunbar Ivy D | title = Pulmonary hypertension in children with Down syndrome | journal = Pediatric Pulmonology | volume = 56 | issue = 3 | pages = 621–629 | date = March 2021 | pmid = 32049444 | doi = 10.1002/ppul.24687 | s2cid = 211087826 }}</ref> Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development, [[endothelial dysfunction]], and proinflammatory genes.<ref name="Bush-2021" /> [[Mitral valve]] problems become common as people age, even in those without heart problems at birth.<ref name=Malt2013/> Other problems that may occur include [[tetralogy of Fallot]] and [[patent ductus arteriosus]].<ref name=Tint2010>{{cite book | vauthors = Tintinalli JE |title=Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)) |publisher=McGraw-Hill Companies |location=New York |year=2010 |pages=Chapter 138|chapter=The Child with Special Health Care Needs|isbn=978-0-07-148480-0}}</ref> People with Down syndrome have a lower risk of [[atherosclerosis|hardening of the arteries]].<ref name=Malt2013/>

===Cancer===
Although the overall risk of [[cancer]] in Down syndrome is not changed,<ref name=UrbanoP129>{{cite book| vauthors = Urbano R |title=Health Issues Among Persons With Down Syndrome|url=https://books.google.com/books?id=QbHL8qrgfCoC&pg=PA129|date=9 September 2010|publisher=Academic Press|isbn=978-0-12-374477-7|page=129|url-status=live|archive-url=https://web.archive.org/web/20150512114141/http://books.google.com/books?id=QbHL8qrgfCoC&pg=PA129|archive-date=12 May 2015}}</ref> the risk of [[testicular cancer]] and certain blood cancers, including [[acute lymphoblastic leukemia]] (ALL) and [[acute megakaryoblastic leukemia]] (AMKL) is increased while the risk of other non-blood cancers is decreased.<ref name=Malt2013/> People with Down syndrome are believed to have an increased risk of developing cancers derived from [[germ cell]]s whether these cancers are blood- or non-blood-related.<ref name=Nix2018/> In 2008, the World Health Organization (WHO) introduced a distinct classification for myeloid proliferation in individuals with Down syndrome.<ref>{{cite journal | vauthors = Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD | display-authors = 6 | title = The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes | journal = Blood | volume = 114 | issue = 5 | pages = 937–951 | date = July 2009 | pmid = 19357394 | doi = 10.1182/blood-2009-03-209262 }}</ref>

==== Blood cancers ====
[[Leukemia]] is 10 to 15 times more common in children with Down syndrome.<ref name=Hick2012/> In particular, [[acute lymphoblastic leukemia]] is 20 times more common and the megakaryoblastic form of [[acute myeloid leukemia]] ([[acute megakaryoblastic leukemia]]), is 500 times more common.<ref name="pmid22867885"/> Acute megakaryoblastic leukemia (AMKL) is a leukemia of [[megakaryoblast]]s, the precursors cells to [[megakaryocyte]]s which form blood [[platelet]]s.<ref name="pmid22867885">{{cite journal | vauthors = Seewald L, Taub JW, Maloney KW, McCabe ER | title = Acute leukemias in children with Down syndrome | journal = Molecular Genetics and Metabolism | volume = 107 | issue = 1–2 | pages = 25–30 | date = September 2012 | pmid = 22867885 | doi = 10.1016/j.ymgme.2012.07.011 }}</ref> Acute lymphoblastic leukemia in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a [[white blood cell count]] greater than 50,000 per [[microliter]] and is rare in those younger than one year old. ALL in Down syndrome tends to have poorer outcomes than other cases of ALL in people without Down syndrome.<ref name="pmid22867885"/><ref name="pmid27285583">{{cite journal | vauthors = Lee P, Bhansali R, Izraeli S, Hijiya N, Crispino JD | title = The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome | journal = Leukemia | volume = 30 | issue = 9 | pages = 1816–1823 | date = September 2016 | pmid = 27285583 | pmc = 5434972 | doi = 10.1038/leu.2016.164 }}</ref>  In short, the likelihood of developing acute myeloid leukemia (AML) and [[acute lymphoblastic leukemia]] (ALL) is higher in children with Down syndrome compared to those without Down syndrome.<ref>{{cite journal | vauthors = Li J, Kalev-Zylinska ML | title = Advances in molecular characterization of myeloid proliferations associated with Down syndrome | journal = Frontiers in Genetics | volume = 13 | article-number = 891214 | date = 2022 | pmid = 36035173 | pmc = 9399805 | doi = 10.3389/fgene.2022.891214 | doi-access = free }}</ref>

[[Myeloid leukemia]] typically precedes Down syndrome and is accompanied by a condition known as [[Transient myeloproliferative disease|transient abnormal myelopoiesis]] (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes.<ref name="The paradox of Myeloid Leukemia ass">{{cite journal | vauthors = Gupte A, Al-Antary ET, Edwards H, Ravindranath Y, Ge Y, Taub JW | title = The paradox of Myeloid Leukemia associated with Down syndrome | journal = Biochemical Pharmacology | volume = 201 | article-number = 115046 | date = July 2022 | pmid = 35483417 | doi = 10.1016/j.bcp.2022.115046 | s2cid = 248431139 }}</ref> In Down syndrome, AMKL is typically preceded by [[transient myeloproliferative disease]] (TMD), a disorder of [[Haematopoiesis|blood cell production]] in which non-cancerous megakaryoblasts with a mutation in the ''[[GATA1]]'' gene rapidly divide during the later period of pregnancy.<ref name="pmid22867885"/><ref name="pmid25956670">{{cite journal | vauthors = Tamblyn JA, Norton A, Spurgeon L, Donovan V, Bedford Russell A, Bonnici J, Perkins K, Vyas P, Roberts I, Kilby MD | display-authors = 6 | title = Prenatal therapy in transient abnormal myelopoiesis: a systematic review | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 101 | issue = 1 | pages = F67–F71 | date = January 2016 | pmid = 25956670 | doi = 10.1136/archdischild-2014-308004 | s2cid = 5958598 | url = https://ora.ox.ac.uk/objects/uuid:73db9b1c-e082-43bc-91a5-db03b26d18d3 }}</ref> GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM.<ref name="pmid27510823"/> In trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to the development of TAM on the preleukemic pathway.<ref name="The paradox of Myeloid Leukemia ass"/> The condition affects 3–10% of babies with Down.<ref name="pmid22867885"/> While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications.<ref name=Gam2012>{{cite journal | vauthors = Gamis AS, Smith FO | title = Transient myeloproliferative disorder in children with Down syndrome: clarity to this enigmatic disorder | journal = British Journal of Haematology | volume = 159 | issue = 3 | pages = 277–287 | date = November 2012 | pmid = 22966823 | doi = 10.1111/bjh.12041 | s2cid = 37593917 | doi-access = free }}</ref> In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.<ref name="pmid22867885"/><ref name=Gam2012/><ref name="pmid27510823">{{cite journal | vauthors = Bhatnagar N, Nizery L, Tunstall O, Vyas P, Roberts I | title = Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update | journal = Current Hematologic Malignancy Reports | volume = 11 | issue = 5 | pages = 333–341 | date = October 2016 | pmid = 27510823 | pmc = 5031718 | doi = 10.1007/s11899-016-0338-x }}</ref>

==== Non-blood cancers ====
People with Down syndrome have a lower risk of all major solid cancers, including those of lung, breast, and cervix, with the lowest relative rates occurring in those aged 50 years or older.<ref name=Nix2018/> This low risk is thought to be due to an increase in the expression of [[tumor suppressor gene]]s present on chromosome 21.<ref>{{cite book|title=Cancer genome and tumor microenvironment |year=2010 |publisher=Springer|location=New York|isbn=978-1-4419-0711-0|page=203|url=https://books.google.com/books?id=x3Lb9Mxl4qcC&pg=PA203|edition=Online-Ausg.| veditors = Thomas-Tikhonenko A |url-status=live|archive-url=https://web.archive.org/web/20150704142502/https://books.google.com/books?id=x3Lb9Mxl4qcC&pg=PA203|archive-date=2015-07-04}}</ref><ref name=Nix2018>{{cite journal | vauthors = Nixon DW | title = Down Syndrome, Obesity, Alzheimer's Disease, and Cancer: A Brief Review and Hypothesis | journal = Brain Sciences | volume = 8 | issue = 4 | page = 53 | date = March 2018 | pmid = 29587359 | pmc = 5924389 | doi = 10.3390/brainsci8040053 | doi-access = free }}</ref> One exception is testicular [[Germ cell tumor|germ cell cancer]] which occurs at a higher rate in Down syndrome.<ref name=Nix2018/>

===Endocrine===
Problems of the [[thyroid gland]] occur in 20–50% of individuals with Down syndrome.<ref name=Malt2013/><ref name=Hick2012/> [[Hypothyroidism|Low thyroid]] is the most common form, occurring in almost half of all individuals.<ref name=Malt2013/> Thyroid problems can be due to a poorly or nonfunctioning thyroid at birth (known as [[congenital hypothyroidism]]) which occurs in 1%<ref name=Nelson2011/> or can develop later due to an attack on the thyroid by the [[immune system]] resulting in [[Graves' disease]] or [[autoimmune hypothyroidism]].<ref>{{cite journal | vauthors = Graber E, Chacko E, Regelmann MO, Costin G, Rapaport R | title = Down syndrome and thyroid function | journal = Endocrinology and Metabolism Clinics of North America | volume = 41 | issue = 4 | pages = 735–745 | date = December 2012 | pmid = 23099267 | doi = 10.1016/j.ecl.2012.08.008 }}</ref> [[Type 1 diabetes mellitus]] is also more common.<ref name=Malt2013/>

===Gastrointestinal===
[[Constipation]] occurs in nearly half of people with Down syndrome and may result in changes in behavior.<ref name=Hick2012/> One potential cause is [[Hirschsprung's disease]], occurring in 2–15%, which is due to a lack of [[Neuron|nerve cells]] controlling the [[colon (anatomy)|colon]].<ref>{{cite journal | vauthors = Moore SW | title = Down syndrome and the enteric nervous system | journal = Pediatric Surgery International | volume = 24 | issue = 8 | pages = 873–883 | date = August 2008 | pmid = 18633623 | doi = 10.1007/s00383-008-2188-7 | s2cid = 11890549 }}</ref> Other congenital problems can include [[duodenal atresia]], [[imperforate anus]] and [[gastroesophageal reflux disease]].<ref name=Tint2010/> [[Celiac disease]] affects about 7–20%.<ref name="Malt2013" /><ref name="Hick2012" />

===Teeth===
People with Down syndrome tend to be more susceptible to [[gingivitis]] as well as early, severe [[Periodontal pathology|periodontal]] disease, [[Acute necrotizing ulcerative gingivitis|necrotising ulcerative gingivitis]], and early [[tooth loss]], especially in the lower front teeth.<ref name="Churchill">{{cite book| vauthors = Cawson RA, Odell EW |title=Cawson's essentials of oral pathology and oral medicine|date=2012|publisher=Churchill Livingstone|location=Edinburgh|isbn=978-0443-10125-0|pages=419–421|edition=8th}}</ref><ref name="Carranza">{{cite book | veditors = Newman MG, Takei HH, Klokkevold PR, Carranza FA |title=Carranza's clinical periodontology|date=2006|publisher=W.B. Saunders Co.|location=Philadelphia|isbn=978-1-4160-2400-2|pages=299, 397, 409, 623|edition=10th}}</ref> While [[Dental plaque|plaque]] and poor [[oral hygiene]] are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors.<ref name="Carranza"/> Research suggests that the severity is likely a result of a weakened immune system.<ref name="Carranza"/><ref name="Mosby">{{cite book | vauthors = Avery DR, Dean JA, McDonald RE |title=Dentistry for the child and adolescent |date=2004 |publisher=Mosby |isbn=978-0-323-02450-1 |edition=8th |location=St. Louis, Mo |pages=164–168, 190–194, 474}}</ref> The weakened immune system also contributes to increased incidence of [[Candidiasis|yeast infections]] in the mouth (from ''[[Candida albicans]]'').<ref name="Mosby"/>

People with Down syndrome also tend to have a more [[alkaline]] [[saliva]] resulting in a greater resistance to [[tooth decay]], despite decreased quantities of saliva,<ref name="ReferenceA">{{cite book| vauthors = Sapp JP, Eversole LR, Wysocki GP |title=Contemporary oral and maxillofacial pathology|date=2002|publisher=Mosby|location=St. Louis|isbn=978-0-323-01723-7|pages=39–40|edition=2nd}}</ref> less effective oral hygiene habits, and higher plaque indexes.<ref name="Churchill"/><ref name="Mosby"/><ref name="ReferenceA"/><ref name="Saunders">{{cite book| vauthors = Regezi JA, Sciubba JJ, Jordan RC |title=Oral Pathology: Clinical Pathologic Correlations|date=2008|publisher=Saunders Elsevier|location=St Louis, Missouri|isbn=978-1-4557-0262-6 |pages=353–354|edition=5th}}</ref>

Higher rates of tooth wear and [[bruxism]] are also common.<ref name="Mosby"/> Other common oral manifestations of Down syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, [[mouth breathing]], narrow [[palate]] with crowded teeth, class III [[malocclusion]] with an underdeveloped maxilla and posterior [[crossbite]], delayed exfoliation of [[baby teeth]] and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth.<ref name="Churchill" /><ref name="Mosby"/><ref name="ReferenceA"/><ref name="Saunders"/> Less common manifestations include [[cleft lip and palate]] and [[enamel hypocalcification]] (20% prevalence).<ref name="Saunders"/>

[[Taurodontism]], an elongation of the pulp chamber, has a high prevalence in people with DS.<ref>{{cite journal | vauthors = Bell J, Civil CR, Townsend GC, Brown RH | title = The prevalence of taurodontism in Down's syndrome | journal = Journal of Mental Deficiency Research | volume = 33 | issue = 6 | pages = 467–476 | date = December 1989 | pmid = 2533267 | doi = 10.1111/j.1365-2788.1989.tb01502.x }}</ref><ref>{{cite journal | vauthors = Rajić Z, Mestrović SR | title = Taurodontism in Down's syndrome | journal = Collegium Antropologicum | volume = 22 | issue = Suppl | pages = 63–67 | date = December 1998 | pmid = 9951142 }}</ref>

===Fertility===
Males with Down syndrome usually do not father children, while females have lower rates of [[fertility]] relative to those who are unaffected.<ref name=Prad2006/> Fertility is estimated to be present in 30–50% of females.<ref name=Nel2010/> [[Menopause]] usually occurs at an earlier age.<ref name=Malt2013/> The poor fertility in males is thought to be due to problems with [[spermatogenesis|sperm development]]; however, it may also be related to not being sexually active.<ref name=Prad2006>{{cite journal | vauthors = Pradhan M, Dalal A, Khan F, Agrawal S | title = Fertility in men with Down syndrome: a case report | journal = Fertility and Sterility | volume = 86 | issue = 6 | pages = 1765.e1–1765.e3 | date = December 2006 | pmid = 17094988 | doi = 10.1016/j.fertnstert.2006.03.071 | s2cid = 32384231 | doi-access = free }}</ref> Without [[preimplantation genetic diagnosis|assisted reproductive technologies]], around half of the children of someone with Down syndrome will also have the syndrome.<ref name=Prad2006/><ref name=Rubin2013/>

==Cause==
{{Main|Genetics of Down syndrome}}

Down syndrome is caused by having three copies of the [[gene]]s on [[chromosome 21]], rather than the usual two.<ref name=Patt2009/><ref name="Lana2011">{{cite journal | vauthors = Lana-Elola E, Watson-Scales SD, Fisher EM, Tybulewicz VL | title = Down syndrome: searching for the genetic culprits | journal = Disease Models & Mechanisms | volume = 4 | issue = 5 | pages = 586–595 | date = September 2011 | pmid = 21878459 | pmc = 3180222 | doi = 10.1242/dmm.008078 }}</ref> The parents of the affected individual are typically genetically normal.<ref name=Steph2010/> Those who have one child with Down syndrome have about a 1% possibility of having a second child with the syndrome, if both parents are found to have normal [[karyotype]]s.<ref name=Nel2010/>

There are three types of causes for Down syndrome:<ref name="www.intellectualdisability.info"/>
# ''Trisomy 21'': 94% of the time Down syndrome is caused by an extra copy of chromosome 21 in all cells,
# ''Translocation'': 4% of cases extra chromosome 21 material is attached to another chromosome,
# ''Mosaic'': 2% of cases involve mixtures of cells, only some of which have extra chromosome 21.

The most common cause (about 92–95% of cases) is a complete extra copy of chromosome 21, resulting in [[trisomy]] 21.<ref name=Rubin2013/><ref name=CDC2013>{{cite web |url=https://www.cdc.gov/ncbddd/birthdefects/DownSyndrome.html |title=Birth Defects, Down Syndrome |website=National Center on Birth Defects and Developmental Disabilities |publisher=[[Centers for Disease Control and Prevention]] |place=US |date=2013-11-06 |url-status=live |archive-url=https://web.archive.org/web/20170728031507/https://www.cdc.gov/ncbddd/birthdefects/DownSyndrome.html |archive-date=2017-07-28 }}</ref> In 1–2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as [[mosaic (genetics)|mosaic]] Down syndrome.<ref name=Nel2010/><ref>{{cite book|title=Treatment & prognosis in pediatrics.|year=2013|publisher=Jaypee Brothers Medical P|isbn=978-93-5090-428-2|page=391|url=https://books.google.com/books?id=LlR5jdVkm8kC&pg=PA391| vauthors = Mandal K |url-status=live|archive-url=https://web.archive.org/web/20170123082941/https://books.google.com/books?id=LlR5jdVkm8kC&pg=PA391|archive-date=2017-01-23}}</ref> The other common mechanisms that can give rise to Down syndrome include: a [[Robertsonian translocation]], [[isochromosome]], or [[ring chromosome]]. These contain additional material from chromosome 21 and occur in about 2.5% of cases.<ref name=Hick2012/><ref name=Nel2010/> An isochromosome results when the two [[q arm|long arms]] of a chromosome separate together rather than the long and [[p-arm|short arm]] separating together during [[meiosis|egg or sperm development]].<ref name=Rubin2013>{{cite book|title=Essentials of Rubin's Pathology|year=2013|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-8132-6|pages=129–131|url=https://books.google.com/books?id=JD7YLArg5ncC&pg=PA130| vauthors = Reisner H |url-status=live|archive-url=https://web.archive.org/web/20170123082320/https://books.google.com/books?id=JD7YLArg5ncC&pg=PA130|archive-date=2017-01-23}}</ref>

===Trisomy 21===
The trisomy 21 version of Down syndrome (also known by the [[karyotype]] 47,XX,+21 for females and 47,XY,+21 for males)<ref name=Flet2007>{{cite book| vauthors = Fletcher-Janzen E, Reynolds CR |title=Encyclopedia of special education: a reference for the education of children, adolescents, and adults with disabilities and other exceptional individuals|year=2007|publisher=John Wiley & Sons|location=New York|isbn=978-0-470-17419-7|page=458|url=https://books.google.com/books?id=7n-tu1Q7jBsC&pg=PA458|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20170123083050/https://books.google.com/books?id=7n-tu1Q7jBsC&pg=PA458|archive-date=2017-01-23}}</ref> is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development, known as [[nondisjunction]].<ref name=Rubin2013/> As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of chromosome 21.<ref name=Patt2009/><ref name=Rubin2013/> About 88% of cases of trisomy 21 result from nonseparation of the chromosomes in the mother, 8% from nonseparation in the father, and 3% after the egg and sperm have merged.<ref name=Zhang>{{cite book| vauthors = Zhang DY, Cheng L |title=Molecular genetic pathology|year=2008|publisher=Humana|location=Totowa, N.J.|isbn=978-1-59745-405-6|page=45|url=https://books.google.com/books?id=F_7QXO0ZBigC&pg=PA45|url-status=live|archive-url=https://web.archive.org/web/20170123083008/https://books.google.com/books?id=F_7QXO0ZBigC&pg=PA45|archive-date=2017-01-23}}</ref>

The root cause of the extra full or partial chromosome is still unknown.<ref name="NDSS-what" /> Most of the time, the extra chromosome results from a random mistake in cell division during early development of the fetus.<ref>{{Cite news |title=Down syndrome - Symptoms and causes |language=en |website=Mayo Clinic |url=https://www.mayoclinic.org/diseases-conditions/down-syndrome/symptoms-causes/syc-20355977 |access-date=2022-03-24}}</ref> The mechanism is not inherited. There is no scientific research which shows that environmental factors or the parents' activities contribute to Down syndrome. The only factor that has been linked to the increased chance of having a baby with Down syndrome is advanced parental age. This is mostly associated with [[advanced maternal age]] but about 10 per cent of cases are associated with advanced [[Paternal age effect|paternal age]].<ref name="Ramasamy">{{cite journal | vauthors = Ramasamy R, Chiba K, Butler P, Lamb DJ | title = Male biological clock: a critical analysis of advanced paternal age | journal = Fertility and Sterility | volume = 103 | issue = 6 | pages = 1402–1406 | date = June 2015 | pmid = 25881878 | pmc = 4955707 | doi = 10.1016/j.fertnstert.2015.03.011 }}</ref>  [[File:Down Syndrome Karyotype.png|thumb|upright=1.4|[[Karyotype]] for Down syndrome (trisomy 21) showing the three copies of [[chromosome 21]]]]

===Translocation Down syndrome===
The extra chromosome 21 material may also occur due to a [[Robertsonian translocation]] in 2–4% of cases.<ref name=Nel2010/><ref name=AK2013/> In this translocation Down syndrome, the long arm of chromosome 21 is attached to another chromosome, often [[Chromosome 14 (human)|chromosome 14]].<ref name=Mich2013/> In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q).<ref name=Mich2013>{{cite book|title=Human Heredity: Principles and Issues|year=2013|publisher=Cengage Learning|isbn=978-1-285-52847-2|page=138|url=https://books.google.com/books?id=KSwLAAAAQBAJ&pg=PA138| vauthors = Cummings M | edition = 10th |url-status=live|archive-url=https://web.archive.org/web/20170123082431/https://books.google.com/books?id=KSwLAAAAQBAJ&pg=PA138|archive-date=2017-01-23}}</ref><ref>{{cite book|title=Yen and Jaffe's reproductive endocrinology: physiology, pathophysiology, and clinical management|year=2009|publisher=Saunders/Elsevier|location=Philadelphia, PA|isbn=978-1-4160-4907-4|page=791|url=https://books.google.com/books?id=NudwnhxY8kYC&pg=PA791| vauthors = Strauss JF, Barbieri RL |edition=6th|url-status=live|archive-url=https://web.archive.org/web/20170123082911/https://books.google.com/books?id=NudwnhxY8kYC&pg=PA791|archive-date=2017-01-23}}</ref> This may be a new mutation or previously present in one of the parents.<ref name=Menk2006/> The parent with such a translocation is usually normal physically and mentally;<ref name=Mich2013/> however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists.<ref name=AK2013>{{cite book|title=Family Medicine Principles and Practice|year=2013|publisher=Springer New York|location=New York, NY|isbn=978-0-387-21744-4|page=142|url=https://books.google.com/books?id=icdGAAAAQBAJ&pg=PA142| vauthors = David AK |edition=Sixth|url-status=live|archive-url=https://web.archive.org/web/20170123082720/https://books.google.com/books?id=icdGAAAAQBAJ&pg=PA142|archive-date=2017-01-23}}</ref> This results in a 15% chance of having a child with Down syndrome when the mother is affected and a less than 5% probability if the father is affected.<ref name=Menk2006/> The probability of this type of Down syndrome is not related to the mother's age.<ref name=Mich2013/> Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome.<ref name=Mich2013/> In this case it is sometimes known as ''familial'' Down syndrome.<ref>{{cite book| veditors = Gardner RJ, Sutherland GR, Shaffer LG |title=Chromosome abnormalities and genetic counseling|year=2012|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-974915-7|page=292|url=https://books.google.com/books?id=mqNpAgAAQBAJ&pg=PA292|edition=4th|url-status=live|archive-url=https://web.archive.org/web/20170123082500/https://books.google.com/books?id=mqNpAgAAQBAJ&pg=PA292|archive-date=2017-01-23}}</ref>

=== Mosaic Down syndrome ===
[[Mosaic (genetics)|Mosaic]] Down syndrome is diagnosed when there is a mixture of two types of cells: some cells have three copies of chromosome 21 but some cells have the typical two copies of chromosome 21.<ref name="CDC"/> This type is the least common form of Down syndrome and accounts for only about 1% of all cases.<ref name="NDSS-what">{{Cite web |title=What is Down Syndrome? {{!}} National Down Syndrome Society |url=https://www.ndss.org/about-down-syndrome/down-syndrome/ |access-date=2022-03-24 |website=NDSS |language=en-US}}</ref> Children with mosaic Down syndrome may have the same features as other children with Down syndrome. However, they may have fewer characteristics of the condition due to the presence of some (or many) cells with a typical number of chromosomes.<ref name="CDC">{{Cite web |date=2021-04-06 |title=Facts about Down Syndrome {{!}} CDC |url=https://www.cdc.gov/ncbddd/birthdefects/downsyndrome.html |access-date=2023-03-31 |website=Centers for Disease Control and Prevention |language=en-us}}</ref>

==Mechanism==
The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21.<ref name=Lana2011/> This overexpression has been estimated at 50%, due to the third copy of the chromosome present.<ref name=Nel2010/> Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3,<ref>{{cite web |url=http://emedicine.medscape.com/article/943216-overview |title=Genetics of Down syndrome |access-date=2011-05-29 |url-status=live |archive-url=https://web.archive.org/web/20110527214124/http://emedicine.medscape.com/article/943216-overview |archive-date=2011-05-27 }}</ref> with this area including genes for the [[amyloid precursor protein]], [[superoxide dismutase]], and likely the [[ETS2]] proto [[oncogene]].<ref>{{cite book|title=Current diagnosis & treatment psychiatry|year=2008|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-142292-5|pages=Chapter 3|edition=2nd| veditors = Ebert MH |chapter=Psychiatric Genetics}}</ref> Other research, however, has not confirmed these findings.<ref name=Lana2011/> [[MicroRNA]]s are also proposed to be involved.<ref>{{cite journal | vauthors = Patterson D, Cabelof DC | title = Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging | journal = Mechanisms of Ageing and Development | volume = 133 | issue = 4 | pages = 133–137 | date = April 2012 | pmid = 22019846 | doi = 10.1016/j.mad.2011.10.001 | s2cid = 3663890 }}</ref>

The dementia that occurs in Down syndrome is due to an excess of [[amyloid beta]] [[peptide]] produced in the brain and is similar to [[Alzheimer's disease]], which also involves amyloid beta build-up.<ref name=Wek2013/> Amyloid beta is processed from amyloid precursor protein, the gene for which is located on chromosome 21.<ref name=Wek2013>{{cite journal | vauthors = Weksler ME, Szabo P, Relkin NR, Reidenberg MM, Weksler BB, Coppus AM | title = Alzheimer's disease and Down's syndrome: treating two paths to dementia | journal = Autoimmunity Reviews | volume = 12 | issue = 6 | pages = 670–673 | date = April 2013 | pmid = 23201920 | doi = 10.1016/j.autrev.2012.10.013 }}</ref> [[Senile plaques]] and [[neurofibrillary tangle]]s are present in nearly all by 35&nbsp;years of age, though dementia may not be present.<ref name=Steph2010/> It is hypothesized that those with Down syndrome lack a normal number of [[lymphocytes]] and produce less [[antibody|antibodies]] which is said to present an increased risk of infection.<ref name=Hick2012/>

===Epigenetics===
Down syndrome is associated with an increased risk of some chronic diseases that are typically associated with older age such as Alzheimer's disease. It is believed that accelerated aging occurs and increases the biological age of tissues, but molecular evidence for this hypothesis is sparse. According to a biomarker of tissue age known as [[epigenetic clock]], it is hypothesized that trisomy 21 increases the age of blood and brain tissue (on average by 6.6 years).<ref name="Horvath2015DownSyndrome">{{cite journal | vauthors = Horvath S, Garagnani P, Bacalini MG, Pirazzini C, Salvioli S, Gentilini D, Di Blasio AM, Giuliani C, Tung S, Vinters HV, Franceschi C | display-authors = 6 | title = Accelerated epigenetic aging in Down syndrome | journal = Aging Cell | volume = 14 | issue = 3 | pages = 491–495 | date = June 2015 | pmid = 25678027 | pmc = 4406678 | doi = 10.1111/acel.12325 }}</ref>

==Diagnosis==
===Screening before birth===
Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age.<ref name=ACOG2007/><ref>{{cite web|title=CG62: Antenatal care |url=http://publications.nice.org.uk/antenatal-care-cg62 |publisher=London: National Institute for Health and Clinical Excellence |access-date=16 February 2013 |author=National Institute for Health and Clinical Excellence |year=2008 |archive-url=https://web.archive.org/web/20130126165543/http://publications.nice.org.uk/antenatal-care-cg62 |archive-date=26 January 2013 }}</ref> A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate.<ref name=Hick2012/> None can be definitive; thus, if screening predicts a high possibility of Down syndrome, either [[amniocentesis]] or [[chorionic villus sampling]] is required to confirm the diagnosis.<ref name=ACOG2007/>

==== Ultrasound ====
[[Prenatal ultrasound]] can be used to screen for Down syndrome. Findings that indicate increased chances when seen at 14 to 24 weeks of [[gestation]] include a small or no nasal bone, [[ventriculomegaly|large ventricles]], [[nuchal fold thickness]], and an abnormal right [[subclavian artery]], among others.<ref name=Aga2013>{{cite journal | vauthors = Agathokleous M, Chaveeva P, Poon LC, Kosinski P, Nicolaides KH | title = Meta-analysis of second-trimester markers for trisomy 21 | journal = Ultrasound in Obstetrics & Gynecology | volume = 41 | issue = 3 | pages = 247–261 | date = March 2013 | pmid = 23208748 | doi = 10.1002/uog.12364 | doi-access = free }}</ref> The presence or absence of many markers is more accurate.<ref name=Aga2013/> Increased fetal [[nuchal translucency]] (NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.<ref>{{cite journal | vauthors = Malone FD, D'Alton ME | title = First-trimester sonographic screening for Down syndrome | journal = Obstetrics and Gynecology | volume = 102 | issue = 5 Pt 1 | pages = 1066–1079 | date = November 2003 | pmid = 14672489 | doi = 10.1016/j.obstetgynecol.2003.08.004 | s2cid = 24592539 }}</ref>

<gallery mode="packed" heights="200px">
T21.JPG|Ultrasound of fetus with Down syndrome showing a [[megacystis|large bladder]]
Nuchal edema in Down Syndrome Dr. W. Moroder.jpg|Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndrome
</gallery>

====Blood tests====
Several blood markers can be measured to predict the chances of Down syndrome during the first or second trimester.<ref name=Can2012/><ref name=Deek2012/> Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results.<ref name=Can2012/> In the second trimester, often two or three tests are used in combination with two or three of: [[α-fetoprotein]], unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases.<ref name=Deek2012>{{cite journal | vauthors = Alldred SK, Deeks JJ, Guo B, Neilson JP, Alfirevic Z | title = Second trimester serum tests for Down's Syndrome screening | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 6 | article-number = CD009925 | date = June 2012 | pmid = 22696388 | pmc = 7086392 | doi = 10.1002/14651858.CD009925 | url = http://eprints.nottingham.ac.uk/31499/1/Second%20trimester%20serum%20tests%20for%20Down%27s%20Syndrome%20screening.pdf | access-date = January 7, 2019 | archive-url = https://web.archive.org/web/20191209234759/http://eprints.nottingham.ac.uk/31499/1/Second%20trimester%20serum%20tests%20for%20Down%27s%20Syndrome%20screening.pdf | archive-date = December 9, 2019 }}</ref>

Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester.<ref name="Mersy 318–29"/><ref>{{cite journal | vauthors = Verweij EJ, van den Oever JM, de Boer MA, Boon EM, Oepkes D | title = Diagnostic accuracy of noninvasive detection of fetal trisomy 21 in maternal blood: a systematic review | journal = Fetal Diagnosis and Therapy | volume = 31 | issue = 2 | pages = 81–86 | year = 2012 | pmid = 22094923 | doi = 10.1159/000333060 | doi-access = free }}</ref> The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high likelihood of trisomy 21.<ref name=Benn2011/> Accuracy has been reported at 98.6% in the first trimester of pregnancy.<ref name=Hick2012/> Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.<ref name=Benn2011>{{cite journal | vauthors = Benn P, Borrell A, Cuckle H, Dugoff L, Gross S, Johnson JA, Maymon R, Odibo A, Schielen P, Spencer K, Wright D, Yaron Y | display-authors = 6 | title = Prenatal Detection of Down Syndrome using Massively Parallel Sequencing (MPS): a rapid response statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, 24 October 2011 | journal = Prenatal Diagnosis | volume = 32 | issue = 1 | pages = 1–2 | date = January 2012 | pmid = 22275335 | doi = 10.1002/pd.2919 | url = http://www.ispdhome.org/public/news/2011/ISPD_RapidResponse_MPS_24Oct11.pdf | s2cid = 42116198 | archive-url = https://web.archive.org/web/20120319105150/http://www.ispdhome.org/public/news/2011/ISPD_RapidResponse_MPS_24Oct11.pdf | archive-date = 2012-03-19 }}</ref>

====Combinations====
{| class="wikitable"
|+ First- and second-trimester screening<ref name=ACOG2007>{{cite journal | title = ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities | journal = Obstetrics and Gynecology | volume = 109 | issue = 1 | pages = 217–227 | date = January 2007 | pmid = 17197615 | doi = 10.1097/00006250-200701000-00054 | author1 = ACOG Committee on Practice Bulletins }}</ref>
|-
!Screen
![[Gestational age (obstetrics)|Week of pregnancy]] when performed
!Detection rate
!False positive
!Description
|-
|Combined test
| 10–13.5&nbsp;wks
| 82–87%
| 5%
|Uses [[ultrasound]] to measure [[nuchal translucency]] in addition to blood tests for free or total beta-hCG and [[pregnancy-associated plasma protein A|PAPP-A]]
|-
|[[Quad screen]]
|15–20&nbsp;wks
|81%
| 5%
|Measures the maternal serum alpha-fetoprotein, unconjugated estriol, hCG, and [[inhibin]]-A
|-
|Integrated test
|15–20&nbsp;wks
|94–96%
|5%
|Is a combination of the quad screen, PAPP-A, and NT
|-
|[[Cell-free fetal DNA]]
|From 10&nbsp;wks<ref name=oxhp>{{cite web|title=Noninvasive prenatal diagnosis of fetal aneuploidy using cell-free fetal nucleic acids in maternal blood|url=https://www.oxhp.com/secure/policy/noninvasive_prenatal_diagnosis_fetal_aneuploidy.pdf|publisher=United Healthcare Oxford|access-date=25 March 2014|url-status=live|archive-url=https://web.archive.org/web/20140307093626/https://www.oxhp.com/secure/policy/noninvasive_prenatal_diagnosis_fetal_aneuploidy.pdf|archive-date=7 March 2014}}</ref>
|96–100%<ref name="Mersy 318–29">{{cite journal | vauthors = Mersy E, Smits LJ, van Winden LA, de Die-Smulders CE, Paulussen AD, Macville MV, Coumans AB, Frints SG | display-authors = 6 | title = Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012 | journal = Human Reproduction Update | volume = 19 | issue = 4 | pages = 318–329 | date = Jul–Aug 2013 | pmid = 23396607 | doi = 10.1093/humupd/dmt001 | doi-access = free }}</ref>
|0.3%<ref>{{cite journal | vauthors = Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, Craig JA, Chudova DI, Devers PL, Jones KW, Oliver K, Rava RP, Sehnert AJ | display-authors = 6 | title = DNA sequencing versus standard prenatal aneuploidy screening | journal = The New England Journal of Medicine | volume = 370 | issue = 9 | pages = 799–808 | date = February 2014 | pmid = 24571752 | doi = 10.1056/nejmoa1311037 | doi-access = free }}</ref>
|A blood sample is taken from the mother by [[venipuncture]] and is sent for DNA analysis.
|}

====Efficacy====
For combinations of ultrasonography and non-genetic blood tests, screening in both the first and second trimesters is better than just screening in the first trimester.<ref name=ACOG2007/> Common screening techniques in use are able to pick up 90–95% of cases, with a false-positive rate of 2–5%.<ref name=Can2012>{{cite journal | vauthors = Canick J | title = Prenatal screening for trisomy 21: recent advances and guidelines | journal = Clinical Chemistry and Laboratory Medicine | volume = 50 | issue = 6 | pages = 1003–1008 | date = June 2012 | pmid = 21790505 | doi = 10.1515/cclm.2011.671 | s2cid = 37417471 }}</ref> If Down syndrome occurs in one in 500 pregnancies with a 90% detection rate and the test used has a 5% false-positive rate, of 28 women who test positive on screening, only one will have a fetus with Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means of 11 women who test positive on screening, only one will have a fetus with Down syndrome.<ref name=Can2012/>

====Invasive genetic testing====
Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of [[miscarriage]] by between 0.5–1%.<ref name=Tab2010>{{cite journal | vauthors = Tabor A, Alfirevic Z | title = Update on procedure-related risks for prenatal diagnosis techniques | journal = Fetal Diagnosis and Therapy | volume = 27 | issue = 1 | pages = 1–7 | year = 2010 | pmid = 20051662 | doi = 10.1159/000271995 | doi-access = free | oclc = 23338607 }}</ref> The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks.<ref name=Tab2010/> 
[[File:Prenatal Down syndrome screening algorithm.png|thumb|An example of an algorithm for determining the indication for prenatal genetic testing of Down syndrome<ref>{{cite web|url=https://www.uptodate.com/contents/should-i-have-a-screening-test-for-down-syndrome-during-pregnancy-beyond-the-basics/print|title=Patient education: Should I have a screening test for Down syndrome during pregnancy? (Beyond the Basics)|website=UpToDate| vauthors = Halliday JV, Messerlian GM, Palomaki GE }}</ref>]]
The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.<ref name=Tab2010/>

===Abortion rates===
About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated.<ref name=Mans1999/> As a result, there is almost no one with Down syndrome in [[Iceland]] and [[Denmark]], where screening is commonplace.<ref name=Slate2018>{{Cite web|url=https://slate.com/human-interest/2018/05/how-down-syndrome-is-redefining-the-abortion-debate.html|title=How Down Syndrome Is Redefining the Abortion Debate| vauthors = Graham R |date=2018-05-31|website=Slate Magazine|language=en|access-date=2019-01-09}}</ref> In the United States, the termination rate after diagnosis is around 75%,<ref name=Slate2018/> but varies from 61 to 93%, depending on the population surveyed.<ref name=Nat2012/> Rates are lower among women who are younger and have decreased over time.<ref name=Nat2012/> When asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.<ref>{{cite journal | vauthors = Choi H, Van Riper M, Thoyre S | title = Decision making following a prenatal diagnosis of Down syndrome: an integrative review | journal = Journal of Midwifery & Women's Health | volume = 57 | issue = 2 | pages = 156–164 | date = Mar–Apr 2012 | pmid = 22432488 | doi = 10.1111/j.1542-2011.2011.00109.x | doi-access = free }}</ref>

===After birth===
A diagnosis can often be suspected based on the child's physical appearance at birth.<ref name=Nelson2011/> An analysis of the child's chromosomes is needed to confirm the diagnosis, and to determine if a [[Chromosomal translocation|translocation]] is present, as this may help determine the chances of the child's parents having further children with Down syndrome.<ref name=Nelson2011/>

==Management==
Efforts such as [[early childhood intervention]], therapies, screening for common medical issues, a good family environment, and work-related training can improve the development of children with Down syndrome and provide good quality of life. Common therapies utilized include physical therapy, occupational therapy and speech therapy.<ref>{{Cite web |title=What are common treatments for Down syndrome? |url=https://www.nichd.nih.gov/health/topics/down/conditioninfo/treatments |access-date=28 March 2023 |website=NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development|date=31 January 2017 }}</ref> Education and proper care can provide a positive [[quality of life]].<ref name=Roi2003/> Typical childhood [[vaccination]]s are recommended.<ref name=Hick2012/>

===Health screening===
{| class="wikitable" style="float:right; margin-left:10px"
|+ Recommended screening
|-
! Testing !! Children<ref name=Bull2011>{{cite journal | vauthors = Bull MJ | title = Health supervision for children with Down syndrome | journal = Pediatrics | volume = 128 | issue = 2 | pages = 393–406 | date = August 2011 | pmid = 21788214 | doi = 10.1542/peds.2011-1605 | doi-access = free }}</ref>!! Adults<ref name=Malt2013/>
|-
| Hearing || 6 months, 12 months, then yearly || 3–5 years
|-
| [[thyroxine|T4]] and [[thyroid stimulating hormone|TSH]] || 6 months, then yearly||
|-
| Eyes || 6 months, then yearly||3–5 years
|-
| Teeth || 2 years, then every 6 months||
|-
| Celiac disease || Between 2 and 3 years of age,<br /> or earlier if symptoms occur||
|-
| [[polysomnography|Sleep study]] || 3 to 4 years, or earlier if symptoms<br /> of [[obstructive sleep apnea]] occur||
|-
| Neck X-rays || Between 3 and 5 years of age||
|}

A number of health organizations have issued recommendations for [[screening (medicine)|screening]] those with Down syndrome for particular diseases.<ref name=Bull2011/> This is recommended to be done systematically.<ref name=Hick2012/>

At birth, all children should get an [[electrocardiogram]] and [[echocardiogram|ultrasound of the heart]].<ref name=Hick2012/> Surgical repair of heart problems may be required as early as three months of age.<ref name=Hick2012/> [[Heart valve]] problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood.<ref name=Hick2012/> Due to the elevated risk of testicular cancer, some recommend checking the person's testicles yearly.<ref name=Malt2013/>

===Cognitive development===
<!-- Hearing and Speech -->
Some people with Down syndrome experience hearing loss. In this instance, [[hearing aids]] or other amplification devices can be useful for language learning.<ref name="Hick2012" /> [[Speech-Language Pathology|Speech therapy]] may be useful and is recommended to be started around nine months of age.<ref name="Hick2012" /> As those with Down syndrome typically have good hand-eye coordination, learning [[sign language]] is a helpful communication tool.<ref name="Reil2012" /> [[Augmentative and alternative communication]] methods, such as pointing, body language, objects, or pictures, are often used to help with communication.<ref name="Price2007">{{cite journal | vauthors = Roberts JE, Price J, Malkin C | title = Language and communication development in Down syndrome | journal = Mental Retardation and Developmental Disabilities Research Reviews | volume = 13 | issue = 1 | pages = 26–35 | year = 2007 | pmid = 17326116 | doi = 10.1002/mrdd.20136 }}</ref> Behavioral issues and mental illness are typically managed with counseling or medications.<ref name="Nelson2011" /><!-- School -->

Education programs before reaching school age may be useful.<ref name=Wei2010/> School-age children with Down syndrome may benefit from [[inclusive education]] (whereby students of differing abilities are placed in classes with their peers of the same age), provided some adjustments are made to the curriculum.<ref>{{cite web|title=Inclusion: Educating Students with Down Syndrome with Their Non-Disabled Peers|url=http://www.kcdsg.org/files/content/Educating%20Students%20with%20Down%20Syndrome%20With%20Their%20Typical%20Peers.pdf|publisher=National Down Syndrome Society|access-date=5 February 2014|url-status=live|archive-url=https://web.archive.org/web/20141127111652/http://www.kcdsg.org/files/content/Educating%20Students%20with%20Down%20Syndrome%20With%20Their%20Typical%20Peers.pdf|archive-date=27 November 2014}}</ref> In the United States, the [[Individuals with Disabilities Education Act]] of 1975 requires public schools generally to allow attendance by students with Down syndrome.<ref>{{cite book| vauthors = New RS, Cochran M |title=Early childhood education an international encyclopedia|year=2007|publisher=Praeger Publishers|location=Westport, Conn.|isbn=978-0-313-01448-2 |page=305 |url=https://books.google.com/books?id=JulOlhMP3JAC&pg=PA305 |url-status=live|archive-url= https://web.archive.org/web/20170123083030/https://books.google.com/books?id=JulOlhMP3JAC&pg=PA305 |archive-date=2017-01-23}}</ref>

<!-- Early Intervention&nbsp;Therapies -->
Individuals with Down syndrome may learn better visually. Drawing may help with language, speech, and reading skills. Children with Down syndrome still often have difficulty with sentence structure and grammar, as well as developing the ability to speak clearly.<ref>{{Cite news|url=https://www.dseinternational.org/en-us/about-down-syndrome/development/|title=Development and learning for people with Down syndrome|language=en-US|access-date=2016-11-18|url-status=live|archive-url=https://web.archive.org/web/20161119055326/https://www.dseinternational.org/en-us/about-down-syndrome/development/|archive-date=2016-11-19}}</ref> Several types of early intervention can help with cognitive development. Efforts to develop motor skills include physical therapy, speech and language therapy, and occupational therapy. Physical therapy focuses specifically on motor development and teaching children to interact with their environment. Speech and language therapy can help prepare for later language. Lastly, occupational therapy can help with skills needed for later independence.<ref>{{Cite web|url=http://www.ndss.org/resources/therapies-development/early-intervention/|title=Early Intervention – National Down Syndrome Society|website=www.ndss.org|access-date=2016-11-18|url-status=live|archive-url=https://web.archive.org/web/20161119060027/http://www.ndss.org/resources/therapies-development/early-intervention/|archive-date=2016-11-19}}</ref>

===Other===
[[Tympanostomy tube]]s are often needed<ref name=Hick2012/> and often more than one set during the person's childhood.<ref name=Rod2012>{{cite journal | vauthors = Rodman R, Pine HS | title = The otolaryngologist's approach to the patient with Down syndrome | journal = Otolaryngologic Clinics of North America | volume = 45 | issue = 3 | pages = 599–629, vii–viii | date = June 2012 | pmid = 22588039 | doi = 10.1016/j.otc.2012.03.010 }}</ref> [[Tonsillectomy]] is also often done to help with sleep apnea and [[pharyngitis|throat infections]].<ref name=Hick2012/> Surgery does not correct every instance of sleep apnea and a [[continuous positive airway pressure]] (CPAP) machine may be useful in those cases.<ref name=Rod2012/>

Efforts to prevent [[respiratory syncytial virus]] (RSV) infection with [[human monoclonal antibodies]] should be considered, especially in those with heart problems.<ref name=Wei2010/> In those who develop dementia there is no evidence for [[memantine]],<ref>{{cite journal | vauthors = Mohan M, Bennett C, Carpenter PK | title = Memantine for dementia in people with Down syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 1 | article-number = CD007657 | date = January 2009 | pmid = 19160343 | pmc = 7197456 | doi = 10.1002/14651858.CD007657 }}</ref> [[donepezil]],<ref>{{cite journal | vauthors = Mohan M, Carpenter PK, Bennett C | title = Donepezil for dementia in people with Down syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 1 | article-number = CD007178 | date = January 2009 | pmid = 19160328 | pmc = 7208846 | doi = 10.1002/14651858.CD007178.pub2 }}</ref> [[rivastigmine]],<ref>{{cite journal | vauthors = Mohan M, Bennett C, Carpenter PK | title = Rivastigmine for dementia in people with Down syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 1 | article-number = CD007658 | date = January 2009 | pmid = 19160344 | pmc = 7197503 | doi = 10.1002/14651858.CD007658 }}</ref> or [[galantamine]].<ref>{{cite journal | vauthors = Mohan M, Bennett C, Carpenter PK | title = Galantamine for dementia in people with Down syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 1 | article-number = CD007656 | date = January 2009 | pmid = 19160342 | pmc = 7197502 | doi = 10.1002/14651858.CD007656 }}</ref>

==Prognosis==
{{Globalize|date=January 2025|2=US and Sweden|section}}[[File:Downs syndrome world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.4|Deaths due to Down syndrome per million persons in 2012 {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0}}{{legend|#ffd820|1}}{{legend|#ffc020|2}}{{legend|#ffa020|3}}{{legend|#ff9a20|4}}{{legend|#f08015|5}}{{legend|#e06815|6}}{{legend|#d85010|7–8}}{{legend|#d02010|9–16}}{{div col end}}]]
Between 5–15% of children with Down syndrome in Sweden attend regular school.<ref name=EU2006/> Some graduate from high school; however, most do not.<ref name=Stein2011/> Of those with intellectual disability in the United States who attended high school about 40% graduated.<ref>{{cite web|title=Number of 14- through 21-year-old students served under Individuals with Disabilities Education Act, Part B, who exited school, by exit reason, age, and type of disability: 2007–08 and 2008–09|url=https://nces.ed.gov/programs/digest/d11/tables/dt11_118.asp|work=National Center for Education Statistics|access-date=7 February 2014|url-status=live|archive-url=https://web.archive.org/web/20140222132619/https://nces.ed.gov/programs/digest/d11/tables/dt11_118.asp|archive-date=22 February 2014}}</ref> Many learn to read and write and some are able to do paid work.<ref name=Stein2011/> In adulthood about 20% in the United States do paid work in some capacity.<ref name=US2013/><ref>{{cite web|title=Down's Syndrome: Employment Barriers|url=http://www.rehacare.com/cipp/md_rehacare/custom/pub/content,oid,15324/lang,2/ticket,g_u_e_s_t/mcat_id,7738/local_lang,2|work=Rehab Care International|access-date=7 February 2014|archive-url=https://web.archive.org/web/20140222065400/http://www.rehacare.com/cipp/md_rehacare/custom/pub/content,oid,15324/lang,2/ticket,g_u_e_s_t/mcat_id,7738/local_lang,2|archive-date=22 February 2014}}</ref> In Sweden, however, less than 1% have regular jobs.<ref name="EU2006">{{cite web|url=http://www.down-syndrome.eu/files/profiles/edsa_sweden.pdf |title=European Down Syndrome Association news |year=2006 |archive-url=https://web.archive.org/web/20140222204153/http://www.down-syndrome.eu/files/profiles/edsa_sweden.pdf |archive-date=22 February 2014 |work=European Down Syndrome Association |access-date=7 February 2014 }}</ref> Many are able to live semi-independently,<ref name=Steph2010/> but they often require help with financial, medical, and legal matters.<ref name=Nelson2011/> Those with mosaic Down syndrome usually have better outcomes.<ref name=Nel2010>{{cite book| vauthors = Nelson MR |title=Pediatrics|year=2011|publisher=Demos Medical|location=New York|isbn=978-1-61705-004-6|page=88|url=https://books.google.com/books?id=8wE1dAYxGhoC&pg=PA88|url-status=live|archive-url=https://web.archive.org/web/20170123082430/https://books.google.com/books?id=8wE1dAYxGhoC&pg=PA88|archive-date=2017-01-23}}</ref>

Individuals with Down syndrome have a higher risk of early death than the general population.<ref name=Hick2012/> This is most often from heart problems or infections.<ref name=Wei2010/><ref name=Malt2013/> Following improved medical care, particularly for heart and [[gastrointestinal problem]]s, the life expectancy has increased.<ref name=Wei2010/> This increase has been from 12 years in 1912,<ref name="Urbano2010108">{{cite book | vauthors = Urbano R |title=Health Issues Among Persons With Down Syndrome|url=https://books.google.com/books?id=QbHL8qrgfCoC&pg=PA108|date=9 September 2010|publisher=Academic Press|isbn=978-0-12-374477-7|page=108|url-status=live|archive-url=https://web.archive.org/web/20150512112441/http://books.google.com/books?id=QbHL8qrgfCoC&pg=PA108|archive-date=12 May 2015}}</ref> to 25 years in the 1980s,<ref name=Wei2010/> to 50 to 60&nbsp;years in the developed world in the 2000s.<ref name=Malt2013/><ref name=Nelson2011/> Data collected between the 1985–2003 showed between 4–12% infants with Down syndrome die in the first year of life.<ref name=Gam2012/> The probability of long-term survival is partly determined by the presence of heart problems. From research at the turn of the century, it tracked those with congenital heart problems, showing 60% survived to at least 10&nbsp;years and 50% survived to at least 30&nbsp;years of age. The research failed to track further aging beyond 30 years.<ref name="Steph2010" /> In those without heart problems, 85% studied survived to at least 10&nbsp;years and 80% survived to at least 30&nbsp;years of age.<ref name=Steph2010/> It is estimated that 10% lived to 70 years of age in the early 2000s.<ref name=Rubin2013/> Much of this data is outdated and life expectancy has drastically improved with more equitable healthcare and continuous advancement of surgical practice.<ref>{{Cite web |title=Survival Rates Improving for Patients with Down Syndrome and Congenital Heart Defects |url=http://www.cardiosmart.org/news/2016/7/survival-rates-improving-for-patients-with-down-syndrome-and-congenital-heart-defects |access-date=2023-03-31 |website=CardioSmart |language=en}}</ref> The [[National Down Syndrome Society]] provides information regarding raising a child with Down syndrome.<ref>{{cite web|title=Where Should I Go From Here?|url=http://www.ndss.org/Resources/New-Expectant-Parents/Where-Should-I-Go-From-Here/|access-date=19 December 2015|url-status=live|archive-url=https://web.archive.org/web/20151222115201/http://www.ndss.org/Resources/New-Expectant-Parents/Where-Should-I-Go-From-Here/|archive-date=22 December 2015 | work = National Down Syndrome Society }}</ref>

==Epidemiology==
[[File:Down risk by maternal age from jk morris.png|thumb|upright=1.5|The risk of having a Down syndrome pregnancy in relation to a [[Advanced maternal age|mother's age]]<ref name=Mor2002>{{cite journal | vauthors = Morris JK, Mutton DE, Alberman E | title = Revised estimates of the maternal age specific live birth prevalence of Down's syndrome | journal = Journal of Medical Screening | volume = 9 | issue = 1 | pages = 2–6 | year = 2002 | pmid = 11943789 | doi = 10.1136/jms.9.1.2 | doi-access = free }}</ref>]]
Down syndrome is the most common chromosomal abnormality in humans.<ref name="Malt2013" /> Globally, {{as of|2010|lc=y}}, Down syndrome occurs in about 1 per 1,000 births<ref name=Wei2010/> and results in about 17,000 deaths.<ref name=Loz2012>{{cite journal | vauthors = Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA | display-authors = 6 | title = Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–2128 | date = December 2012 | pmid = 23245604 | pmc = 10790329 | doi = 10.1016/S0140-6736(12)61728-0 | hdl-access = free | s2cid = 1541253 | hdl = 10536/DRO/DU:30050819 }}</ref> More children are born with Down syndrome in countries where abortion is not allowed and in countries where pregnancy more commonly occurs at a later age.<ref name=Wei2010/> About 1.4 per 1,000 live births in the United States<ref name=Parker2010>{{cite journal | vauthors = Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A | display-authors = 6 | title = Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006 | journal = Birth Defects Research. Part A, Clinical and Molecular Teratology | volume = 88 | issue = 12 | pages = 1008–1016 | date = December 2010 | pmid = 20878909 | doi = 10.1002/bdra.20735 }}</ref> and 1.1 per 1,000 live births in Norway are affected.<ref name=Malt2013/> In the 1950s, in the United States, it occurred in 2 per 1,000 live births with the decrease since then due to prenatal screening and abortions.<ref name=Menk2006>{{cite book| vauthors = Menkes JH, Sarnat HB |title=Child neurology|year=2005|publisher=Lippincott Williams & Wilkins|location=Philadelphia, PA|isbn=978-0-7817-5104-9|page=228|url=https://books.google.com/books?id=gnjMX_jtvYoC&pg=PA228|edition=7th|url-status=live|archive-url=https://web.archive.org/web/20170123082801/https://books.google.com/books?id=gnjMX_jtvYoC&pg=PA228|archive-date=2017-01-23}}</ref> The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting.<ref name=Nelson2011/> It is the cause of 8% of all [[congenital disorders]].<ref name=Wei2010/>

[[Maternal age effect|Maternal age]] affects the chances of having a pregnancy with Down syndrome.<ref name=Mor2002/> At age 20, the chance is 1 in 1,441; at age 30, it is 1 in 959; at age 40, it is 1 in 84; and at age 50 it is 1 in 44.<ref name=Mor2002/> Although the probability increases with maternal age, 70% of children with Down syndrome are born to women 35 years of age and younger, because younger people have more children.<ref name=Mor2002/> The [[Paternal age effect|father's older age]] is also a risk factor in women older than 35, but not in women younger than 35, and may partly explain the increase in risk as women age.<ref name=Doug2013>{{cite book | vauthors = Fisch H | chapter = The male biological clock |title=Paternal influences on human reproductive success|year=2013|publisher=Cambridge University Press|isbn=978-1-107-02448-9|page=65| chapter-url = https://books.google.com/books?id=O4Px3Q7f34QC&pg=PA65| veditors = Carrell DT |url-status=live|archive-url=https://web.archive.org/web/20170123082733/https://books.google.com/books?id=O4Px3Q7f34QC&pg=PA65|archive-date=2017-01-23}}</ref>

==History==
[[File:The Adoration of the Christ Child MET DT8852.jpg|thumb|Levitas and Reid have suggested that this [[early Netherlandish painting]], ''The Adoration of the Christ Child'', depicts a person with Down syndrome as one of the angels.<ref>{{cite journal | vauthors = Levitas AS, Reid CS | title = An angel with Down syndrome in a sixteenth century Flemish Nativity painting | journal = American Journal of Medical Genetics. Part A | volume = 116A | issue = 4 | pages = 399–405 | date = February 2003 | pmid = 12522800 | doi = 10.1002/ajmg.a.10043 | quote = We have identified a 16th-century Flemish Nativity painting in which one angelic figure appears distinctly different from other individuals in the painting with an appearance of Down syndrome. | s2cid = 8821338 }}</ref>]]
[[File:Portrait of John Langdon Down (c 1870) by Sydney Hodges.jpg|thumb|left|[[John Langdon Down|John Langdon Haydon Down]] — first described Down syndrome]]

The English physician [[John Langdon Down]] first described Down syndrome in 1862, recognizing it as a distinct type of mental disability, and again in a more widely published report in 1866.<ref name=Hick2012/><ref>{{cite journal|year= 1866|title= Observations on an ethnic classification of idiots|url= http://www.neonatology.org/classics/down.html|journal= Clinical Lecture Reports, London Hospital|volume= 3|pages= 259–62| vauthors = Down JL |access-date= 2006-07-14|url-status= live|archive-url= https://web.archive.org/web/20060615010343/http://www.neonatology.org/classics/down.html|archive-date= 2006-06-15}}</ref><ref>{{cite book|title=John Langdon Down, 1828–1896|publisher=Royal Society of Medicine Press|year=1998|isbn=978-1-85315-374-7| vauthors = Conor WO }}</ref> [[Édouard Séguin]] described it as separate from [[cretinism]] in 1844.<ref name=Evans2009p12/><ref name="Neri2009">{{cite journal | vauthors = Neri G, Opitz JM | title = Down syndrome: comments and reflections on the 50th anniversary of Lejeune's discovery | journal = American Journal of Medical Genetics. Part A | volume = 149A | issue = 12 | pages = 2647–2654 | date = December 2009 | pmid = 19921741 | doi = 10.1002/ajmg.a.33138 | s2cid = 12945876 }}</ref> By the 20th century, Down syndrome had become the most recognizable form of mental disability.

Due to his perception that children with Down syndrome shared facial similarities with those of [[Mongoloid|Blumenbach's Mongoloid race]], John Langdon Down used the term "[[Mongolian idiocy|mongoloid]]".<ref>{{cite book | vauthors = Reisner H | date = 2013 | title = Essentials of Rubin's Pathology | publisher = Lippincott Williams & Wilkins | pages = 129–131 | isbn = 978-1-4511-8132-6}}</ref> He felt that the existence of Down syndrome confirmed that all peoples were genetically related.<ref>{{cite book | vauthors = Gould S | date = 2010 | title = The Panda's Thumb: More Reflections in Natural History | publisher = W. W. Norton & Company | page = 166 | isbn = 978-0-393-34083-9 }}</ref> In the 1950s with discovery of the underlying cause as being related to chromosomes, concerns about the race-based nature of the name increased.<ref>{{cite book | vauthors = Keevak M | date = 2011 | title = Becoming Yellow: A Short History of Racial Thinking | publisher = Princeton University Press | page = 120 | isbn = 
978-1-4008-3860-8 }}</ref>

In 1961, a group of nineteen scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term".<ref name="Rod2011" /> The [[World Health Organization]] (WHO) dropped the term in 1965 after a request by the delegation from the [[Mongolian People's Republic]].<ref name="pmid153994">{{cite journal | vauthors = Howard-Jones N | title = On the diagnostic term "Down's disease" | journal = Medical History | volume = 23 | issue = 1 | pages = 102–4 | date = January 1979 | pmid = 153994 | pmc = 1082401 | doi = 10.1017/s0025727300051048 }}</ref> While this terminology continued to be used until the late twentieth century,<ref>{{Cite book | vauthors = Driscoll MW |title=The Whites are Enemies of Heaven: Climate Caucasianism and Asian Ecological Protection |date=2020 |publisher=[[Duke University Press]] |isbn=978-1-4780-1121-7 |location=Durham}}</ref>{{Rp|page=21}} it is now considered unacceptable and is no longer in common use.

In antiquity, many infants with disabilities were either killed or abandoned.<ref name=Evans2009p12/> 
In June 2020, the earliest incidence of Down syndrome was found in genomic evidence from an infant that was buried before 3200&nbsp;BC at [[Poulnabrone dolmen]] in [[Ireland]].<ref>{{cite web |url=https://www.rte.ie/news/2020/0617/1148049-genomes-study/|title=Genetics study shines light on early periods of Ireland's human history|author=<!--Not stated--> |date= 17 June 2020|website= www.rte.ie|publisher=Raidió Teilifís Éireann |access-date= 17 June 2020}}</ref>
Researchers believe that a number of historical pieces of art portray Down syndrome, including pottery from the [[pre-Columbian]] Tumaco-La Tolita culture in present-day [[Colombia]] and [[Ecuador]],<ref name="BernalBriceno">{{cite journal | vauthors = Bernal JE, Briceno I | title = Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador | journal = Clinical Genetics | volume = 70 | issue = 3 | pages = 188–191 | date = September 2006 | pmid = 16922718 | doi = 10.1111/j.1399-0004.2006.00670.x | s2cid = 27716271 }}</ref> and the 16th-century painting ''The Adoration of the Christ Child''.<ref>{{cite book | vauthors = Evans-Martin FF | title = Down Syndrome | url = https://books.google.com/books?id=BJf2JgWbYoYC | series = Genes & Disease | location = New York | publisher = Infobase Publishing | date = 2009 | page = 13 | isbn = 978-1-4381-1950-2 | access-date = 20 March 2020 | quote = There is also very little representation of Down syndrome in art over the centuries. Only a few paintings, such as the sixteenth century Flemish painting ''The Adoration of the Christ Child'', have been identified in which characters appear to have facial features and other characteristics typical of Down syndrome.}}</ref><ref name=Evans2009p1314>{{cite book| vauthors = Evans-Martin FF |title=Down Syndrome|year=2009|publisher=Chelsea House|location=New York|isbn=978-1-4381-1950-2|pages=[https://archive.org/details/downsyndrome0000evan/page/13 13]–14|url=https://archive.org/details/downsyndrome0000evan|url-access=registration}}</ref>

In the 20th century, many individuals with Down syndrome were institutionalized, few of the associated medical problems were treated, and most people died in infancy or early adulthood. With the rise of the [[eugenics movement]], 33 of the then 48 [[U.S. state]]s and several countries began programs of forced sterilization of individuals with Down syndrome and comparable degrees of disability. [[Action T4]] in [[Nazi Germany]] saw the systematic murder of people with Down syndrome made public policy.<ref name="Wright2011">{{cite book| vauthors = Wright D |title= Downs: The history of a disability |url= https://books.google.com/books?id=0FMKNv_ALRYC&pg=PA200|access-date= 25 August 2012|date=25 August 2011|publisher= Oxford University Press|isbn= 978-0-19-956793-5|pages= 104–108|url-status= live|archive-url= https://web.archive.org/web/20130528115732/http://books.google.com/books?id=0FMKNv_ALRYC&pg=PA200|archive-date= 28 May 2013}}</ref>

With the discovery of [[karyotype]] techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape.<ref name=Neri2009/> In 1959 [[Jérôme Lejeune]] reported the discovery that Down syndrome resulted from an extra chromosome.<ref name=Hick2012/> However, Lejeune's claim to the discovery has been disputed,<ref>{{cite book| vauthors = Wright D |title= Downs: The history of a disability|url= https://books.google.com/books?id=0FMKNv_ALRYC&pg=PA200|access-date= 25 August 2012|date= 25 August 2011|publisher= Oxford University Press|isbn=978-0-19-956793-5|page=145|url-status=live|archive-url=https://web.archive.org/web/20130528115732/http://books.google.com/books?id=0FMKNv_ALRYC&pg=PA200|archive-date= 28 May 2013}}</ref> and in 2014 the Scientific Council of the French Federation of Human Genetics unanimously awarded its Grand Prize to his colleague [[Marthe Gautier]] for her role in this discovery.<ref>{{cite news|title= Trisomie: une pionnière intimidée|url=http://www.lemonde.fr/sciences/article/2014/02/03/trisomie-une-pionniere-intimidee_4359331_1650684.html|access-date=25 March 2014|newspaper= Le Monde|date= Feb 3, 2014 |language=fr}}</ref> The discovery took place in the laboratory of [[Raymond Turpin]] at the Hôpital Trousseau in Paris, France.<ref>{{Cite journal| vauthors = Gautier M, Harper PS |year= 2009|title= Fiftieth anniversary of trisomy 21: returning to a discovery|url= http://www.hopkinsmedicine.org/women_science_medicine/_pdfs/Trisomy%2021%20article.pdf|journal= Human Genetics|volume= 126|issue= 2|pages= 317–324|doi= 10.1007/s00439-009-0690-1|s2cid= 30299551|url-status= live|archive-url= https://web.archive.org/web/20170202012842/http://www.hopkinsmedicine.org/women_science_medicine/_pdfs/Trisomy%2021%20article.pdf|archive-date= 2017-02-02}}</ref> Jérôme Lejeune and Marthe Gautier were both his students.<ref>{{cite journal | vauthors = Pain E | title = History of science. After more than 50 years, a dispute over Down syndrome discovery | journal = Science | volume = 343 | issue = 6172 | pages = 720–721 | date = February 2014 | pmid = 24531949 | doi = 10.1126/science.343.6172.720 | doi-access = free | bibcode = 2014Sci...343..720P }}</ref>

As a result of this discovery, the condition became known as trisomy&nbsp;21.<ref>{{cite book| vauthors = Wright D |title= Downs: The history of a disability |url= https://books.google.com/books?id=0FMKNv_ALRYC&pg=PA200|access-date= 25 August 2012|date= 25 August 2011|publisher= Oxford University Press|isbn= 978-0-19-956793-5|pages= 9–10|url-status= live|archive-url= https://web.archive.org/web/20130528115732/http://books.google.com/books?id=0FMKNv_ALRYC&pg=PA200|archive-date= 28 May 2013}}</ref> Even before the discovery of its cause, the presence of the syndrome in all races, its association with older maternal age, and its rarity of recurrence had been noticed. Medical texts had assumed it was caused by a combination of inheritable factors that had not been identified. Other theories had focused on injuries sustained during birth.<ref>{{cite book | vauthors = Warkany J |title= Congenital Malformations |location= Chicago |publisher= Year Book Medical Publishers, Inc |year= 1971 |pages= 313–14|isbn= 978-0-8151-9098-1}}</ref>
{{clear}}

==Society and culture==
{{See also|List of people with Down syndrome}}

===Name===
Down syndrome is named after [[John Langdon Down]]. He was the first person to provide an accurate description of the syndrome. His research that was published in 1866 earned him the recognition as the Father of the syndrome.<ref>{{Cite web |title=About Down Syndrome |url=https://ndss.org/about |access-date=28 March 2023 |website=National Down Syndrome Society}}</ref> While others had previously recognized components of the condition, John Langdon Down described the syndrome as a distinct, unique medical condition.<ref name="NDDS-about" />

In 1975, the United States [[National Institutes of Health]] (NIH) convened a conference to standardize the naming and recommended replacing the possessive form, "Down's syndrome", with "Down syndrome".<ref>{{cite journal | vauthors =  | title = Classification and nomenclature of morphological defects | journal = Lancet | volume = 1 | issue = 7905 | page = 513 | date = March 1975 | pmid = 46972 | doi = 10.1016/S0140-6736(75)92847-0 | s2cid = 37636187 }}</ref> However, both the possessive and nonpossessive forms remain in use by the general population,<ref name=Smith-2011>{{cite book| vauthors = Smith K |title=The politics of Down syndrome|year=2011|publisher=Zero|location=[New Alresford, Hampshire]|isbn=978-1-84694-613-4|page=3|url=https://books.google.com/books?id=wSWzQyUZJxUC&pg=PA3|url-status=live|archive-url=https://web.archive.org/web/20170123082433/https://books.google.com/books?id=wSWzQyUZJxUC&pg=PA3|archive-date=2017-01-23}}</ref> and in the United Kingdom the [[National Health Service|NHS]] uses the term ''Down's syndrome'' in its patient-oriented information.<ref>{{cite web |title=Down's syndrome |url=https://www.nhs.uk/conditions/downs-syndrome/ |website=nhs.uk |access-date=27 October 2025 |language=en |date=23 October 2017}}</ref> The term "trisomy 21" is also commonly used.<ref name="Rod2011">{{cite journal | vauthors = Rodríguez-Hernández ML, Montoya E | title = Fifty years of evolution of the term Down's syndrome | journal = Lancet | volume = 378 | issue = 9789 | page = 402 | date = July 2011 | pmid = 21803206 | doi = 10.1016/s0140-6736(11)61212-9 | s2cid = 8541289 }}</ref><ref>{{cite book| vauthors = Westman JS |title=Medical genetics for the modern clinician.|year=2005|publisher=Lippincott Williams & Wilkins|location=Philadelphia, PA|isbn=978-0-7817-5760-7|page=[https://archive.org/details/medicalgeneticsf0000west/page/136 136]|url=https://archive.org/details/medicalgeneticsf0000west|url-access=registration}}</ref>

===Ethics===
Obstetricians routinely offer antenatal screenings for various conditions, including Down syndrome.<ref name=Cher2010>{{cite journal | vauthors = Chervenak FA, McCullough LB | title = Ethical considerations in first-trimester Down syndrome risk assessment | journal = Current Opinion in Obstetrics & Gynecology | volume = 22 | issue = 2 | pages = 135–138 | date = April 2010 | pmid = 20125014 | doi = 10.1097/gco.0b013e3283374a9f | s2cid = 2017130 }}</ref><ref>{{Cite journal |last1=Ravitsky |first1=Vardit |last2=Roy |first2=Marie-Christine |last3=Haidar |first3=Hazar |last4=Henneman |first4=Lidewij |last5=Marshall |first5=John |last6=Newson |first6=Ainsley J. |last7=Ngan |first7=Olivia M.Y. |last8=Nov-Klaiman |first8=Tamar |date=2021-08-31 |title=The Emergence and Global Spread of Noninvasive Prenatal Testing |journal=Annual Review of Genomics and Human Genetics |language=en |volume=22 |issue=1 |pages=309–338 |doi=10.1146/annurev-genom-083118-015053 |issn=1527-8204|doi-access=free |pmid=33848430 }}</ref> When results from testing become available, it is considered an ethical requirement to share the results with the patient.<ref name=Cher2010/><ref>{{cite journal | vauthors = Sharma G, McCullough LB, Chervenak FA | title = Ethical considerations of early (first vs. second trimester) risk assessment disclosure for trisomy 21 and patient choice in screening versus diagnostic testing | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 145C | issue = 1 | pages = 99–104 | date = February 2007 | pmid = 17299736 | doi = 10.1002/ajmg.c.30118 | doi-access = free }}</ref>

Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being.<ref>{{cite journal | vauthors = Savulescu J, Kahane G | title = The moral obligation to create children with the best chance of the best life | journal = Bioethics | volume = 23 | issue = 5 | pages = 274–290 | date = June 2009 | pmid = 19076124 | doi = 10.1111/j.1467-8519.2008.00687.x | s2cid = 13897639 }}</ref> One criticism of this reasoning is that it often values those with disabilities less.<ref>{{cite journal | vauthors = Bennett R | title = The fallacy of the Principle of Procreative Beneficence | journal = Bioethics | volume = 23 | issue = 5 | pages = 265–273 | date = June 2009 | pmid = 18477055 | doi = 10.1111/j.1467-8519.2008.00655.x | s2cid = 7373407 | url = https://pure.manchester.ac.uk/ws/files/20431080/POST-PEER-REVIEW-NON-PUBLISHERS.DOC | url-access = subscription }}</ref> Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide.<ref>{{Cite web|title = Halifax mom questions Down syndrome suppression|url = http://www.cbc.ca/news/canada/nova-scotia/halifax-mom-questions-down-syndrome-suppression-1.1323401|access-date = 2015-09-26|url-status=live|archive-url = https://web.archive.org/web/20151105024307/http://www.cbc.ca/news/canada/nova-scotia/halifax-mom-questions-down-syndrome-suppression-1.1323401|archive-date = 2015-11-05}}</ref><ref>{{Cite web|title = Should Down Syndrome Be Cured?|url = http://parenting.blogs.nytimes.com/2010/01/11/should-down-syndrome-be-cured/|access-date = 2015-09-26| vauthors = Belkin L |url-status=live|archive-url = https://web.archive.org/web/20150425093102/http://parenting.blogs.nytimes.com/2010/01/11/should-down-syndrome-be-cured/|archive-date = 2015-04-25|date = 2010-01-11}}</ref> The [[Disability rights|disability rights movement]] does not have a position on screening,<ref name=Paren2003/> although some members consider testing and abortion discriminatory.<ref name=Paren2003>{{cite journal | vauthors = Parens E, Asch A | title = Disability rights critique of prenatal genetic testing: reflections and recommendations | journal = Mental Retardation and Developmental Disabilities Research Reviews | volume = 9 | issue = 1 | pages = 40–47 | year = 2003 | pmid = 12587137 | doi = 10.1002/mrdd.10056 }}</ref> Some in the United States who are [[anti-abortion]] support abortion if the fetus is disabled, while others do not.<ref name=Green1997>{{cite journal | vauthors = Green RM | title = Parental autonomy and the obligation not to harm one's child genetically | journal = The Journal of Law, Medicine & Ethics | volume = 25 | issue = 1 | pages = 5–15, 2 | date = Spring 1997 | pmid = 11066476 | doi = 10.1111/j.1748-720x.1997.tb01389.x | s2cid = 38939256 | url = https://zenodo.org/record/1230726 }}</ref> Of a group of 40 mothers in the United States who have had one child with Down syndrome, half agreed to screening in the next pregnancy.<ref name=Green1997/>

Within the US, some [[Protestant]] denominations see abortion as acceptable when a fetus has Down syndrome while [[Eastern Orthodox Church|Orthodox Christianity]] and [[Roman Catholics|Roman Catholicism]] do not.<ref name=Rel2013>{{cite book|title=Encyclopedia of religious controversies in the United States.|year=2013|publisher=ABC-CLIO|location=Santa Barbara, Calif.|isbn=978-1-59884-867-0|page=278|url=https://books.google.com/books?id=vnWE00YVeJQC&pg=PA278|author-link1=Bill J. Leonard|author-link2=Jill Y. Crainshaw| vauthors = Leonard BJ, Crainshaw JY |edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20170123082425/https://books.google.com/books?id=vnWE00YVeJQC&pg=PA278|archive-date=2017-01-23}}</ref> Women may face disapproval whether they choose abortion or not.<ref>{{cite book|title=Woman-centered care in pregnancy and childbirth|year=2010|publisher=Radcliffe Pub.|location=Oxford|isbn=978-1-84619-161-9|page=140|url=https://books.google.com/books?id=OFvr9oIt1tsC&pg=PA140| vauthors = Shields SG, Candib LM |url-status=live|archive-url=https://web.archive.org/web/20170123082811/https://books.google.com/books?id=OFvr9oIt1tsC&pg=PA140|archive-date=2017-01-23}}</ref> Some of those against screening refer to it as a form of [[eugenics]].<ref name=Rel2013/>

===Advocacy groups===

Advocacy groups for individuals with Down syndrome began to be formed after the [[World War II|Second World War]].<ref name="Adv2011">{{cite book | chapter = Into the Mainstream |title=Downs: The history of a disability|year=2011|publisher=Oxford University Press|isbn=978-0-19-161978-6|page=147| chapter-url = https://books.google.com/books?id=lm0BrR0POj8C&pg=PA147| vauthors = Wright D |url-status=live|archive-url=https://web.archive.org/web/20170123083050/https://books.google.com/books?id=lm0BrR0POj8C&pg=PA147|archive-date=2017-01-23}}</ref> These were organizations advocating for the inclusion of people with Down syndrome into the general school system and for a greater understanding of the condition among the general population,<ref name="Adv2011" /> as well as groups providing support for families with children living with Down syndrome.<ref name="Adv2011" /> Before this individuals with Down syndrome were often placed in [[History of psychiatric institutions|mental hospitals or asylums]]. Organizations included the [[Mencap|Royal Society for Handicapped Children and Adults]] founded in the UK in 1946 by [[Judy Fryd]],<ref name="Adv2011" /><ref>{{cite web|title=Timeline|url=http://www.mencap.org.uk/about-us/our-history/timeline|work=MENCAP|access-date=2 February 2014|archive-url=https://web.archive.org/web/20110617061939/http://www.mencap.org.uk/about-us/our-history/timeline|archive-date=17 June 2011}}</ref> Kobato Kai founded in Japan in 1964,<ref name="Adv2011" /> the National Down Syndrome Congress founded in the United States in 1973 by [[Kathryn McGee]] and others,<ref name="Adv2011" /><ref>{{cite web|title=National Down Syndrome Organizations in the U.S.|url=http://www.globaldownsyndrome.org/about-down-syndrome/resources/national-down-syndrome-organizations-2/|work=Global Down Syndrome Foundation|access-date=2 February 2014|url-status=live|archive-url=https://web.archive.org/web/20140118014934/http://www.globaldownsyndrome.org/about-down-syndrome/resources/national-down-syndrome-organizations-2/|archive-date=18 January 2014|date=2012-02-21}}</ref> and the [[National Down Syndrome Society]] founded in 1979 in the United States.<ref name="Adv2011" /> The first Roman Catholic order of nuns for women with Down Syndrome, [[Little Sisters Disciples of the Lamb]], was founded in 1985 in France.<ref name="vatican">{{cite news | title = Religious Sisters with Down syndrome: the joy of shared contemplative life | vauthors = Vet C | date = July 24, 2019 | access-date = July 31, 2019 | publisher = Vatican News | url = https://www.vaticannews.va/en/world/news/2019-07/stories-religious-sisters-with-down-syndrome.html }}</ref>

The first [[World Down Syndrome Day]] was held on 21 March 2006.<ref name=WDSD2014>{{cite web|title=World Down Syndrome Day|url=http://www.ds-int.org/world-down-syndrome-day|work=Down Syndrome International| access-date=2 February 2014|url-status=live|archive-url=https://web.archive.org/web/20140314001941/http://www.ds-int.org/world-down-syndrome-day|archive-date=14 March 2014}}</ref> The day and month were chosen to correspond with 21 and trisomy, respectively.<ref>{{cite book| vauthors = Pratt G, Rosner V |title=The global and the intimate feminism in our time|year=2012|publisher=Columbia University Press|location=New York|isbn=978-0-231-52084-3|page=113|url=https://books.google.com/books?id=bWGPe649QjIC&pg=PA113 |url-status=live|archive-url= https://web.archive.org/web/20170123082556/https://books.google.com/books?id=bWGPe649QjIC&pg=PA113 |archive-date=2017-01-23}}</ref> It was recognized by the [[United Nations General Assembly]] in 2011.<ref name=WDSD2014/>

Special21.org, founded in 2015, advocates the need for a specific classification category to enable Down syndrome swimmers the opportunity to qualify and compete at the [[Paralympic Games]].<ref>{{Cite web|url=https://www.portugalresident.com/special21-celebrates-world-down-syndrome-day-in-albufeira/|title=Special21 celebrates World Down Syndrome Day in Albufeira|publisher=Portugal Resident|date=March 25, 2022|access-date=March 13, 2024}}</ref>  The project began when International Down syndrome swimmer Filipe Santos broke the world record in the 50m butterfly event, but was unable to compete at the Paralympic Games.<ref>{{Cite web|url=https://www.portugalresident.com/algarve-swimmer-with-down-syndrome-breaks-world-record/|title=Algarve swimmer with Down syndrome breaks world record|publisher=Portugal Resident|date=February 27, 2019|access-date=March 13, 2024}}</ref><ref>{{Cite web|url=https://special21.org/sobre-nos/
|title=Special21 About Us|publisher=Special21.org|access-date=March 13, 2024}}</ref>

===Paralympic Swimming===

[[International Paralympic Committee]] [[Para-swimming classification]] codes are based upon single impairment only, whereas Down syndrome individuals have both physical and intellectual impairments.

Although Down syndrome swimmers are able to compete in the [[Para swimming|Paralympic Swimming]] [[S14 (classification)|S14]] intellectual impairment category (provided they score low in IQ tests), they are often outmatched by the superior physicality of their opponents.<ref>{{Cite web|url=https://www.insidethegames.biz/articles/1117707/ipc-athletes-downs-syndrome-paralympics|title=IPC urged to allow greater numbers of athletes with Down's syndrome to compete at Paralympics|publisher=Insidethegames.biz|author=Liam Morgan|date=January 12, 2022|access-date=March 2, 2024}}</ref><ref>{{Cite web|url=https://www.mirror.co.uk/sport/other-sports/paralympics-calls-down-syndrome-category-28545992|title=Paralympics faces calls for Down's syndrome category to ensure level playing field|publisher=Mirror|author=Liam Llewellyn|date=November 21, 2022|access-date=February 10, 2024}}</ref>

At present there is no designated Paralympic category for swimmers with Down syndrome, meaning they have to compete as intellectually disadvantaged athletes. This disregards their physical disabilities.<ref>{{Cite web|url=https://mashable.com/article/down-syndrome-athletes-paralympics|title=Athletes with Down syndrome fight for inclusion at the Paralympics|publisher=Mashable.com|author=Ariel Bogle|date=August 29, 2016|access-date=March 2, 2024}}</ref><ref>{{Cite web|url=https://www.skysports.com/more-sports/olympics/news/29177/12563240/paralympic-dream-for-british-down-syndrome-swimmers-at-first-national-championships|title=Paralympic dream for British Down syndrome swimmers at first national championships|publisher=Sky Sports|author=Rebecca Williams|date=March 11, 2022|access-date=March 2, 2024}}</ref>

A number of advocacy groups globally have been lobbying for the inclusion of a distinct classification category for Down syndrome swimmers within the IPC Classification Codes framework.<ref>{{Cite web|url=https://www.portugalresident.com/special21-celebrates-world-down-syndrome-day-in-albufeira/|title=Special21 celebrates World Down Syndrome Day in Albufeira|publisher=Portugal Resident|date=March 25, 2022|access-date=March 2, 2024}}</ref>

Despite ongoing advocacy, the issue remains unresolved, and swimmers with Down syndrome continue to face challenges in accessing appropriate classification pathways.<ref>{{Cite web|url=https://www.dsiso.org/paralympics-participation-swimmers-with-down-syndrome/|title=Paralympics Participation swimmers with Down syndrome|publisher=Down Syndrome International Swimming Organisation|author=Emily Laurence|access-date=March 2, 2024}}</ref><ref>{{Cite web|url=https://www.mirror.co.uk/sport/other-sports/paralympics-calls-down-syndrome-category-28545992|title=Paralympics faces calls for Down's syndrome category to ensure level playing field|publisher=Mirror|author=Liam Llewellyn|date=November 21, 2022|access-date=March 2, 2024}}</ref>

==Research==
{{See also|Down syndrome research|Mouse models of Down syndrome}}
The additional copy of chromosome 21 affects the regulation of other genes, creating a complex set of changes. Mechanisms connecting the genetic defect to pathology remain unclear. While applying [[gene therapy]] seems like a promising approach, tailored treatments may be required.<ref>{{cite book | vauthors = Fillat C, Altafaj X |title=Down Syndrome: From Understanding the Neurobiology to Therapy |chapter=Gene therapy for Down syndrome |series=Progress in Brain Research |date=2012 |volume=197 |pages=237–47 |doi=10.1016/B978-0-444-54299-1.00012-1 |pmid=22541296|isbn=978-0-444-54299-1 }}</ref>
Gene therapy delivered via [[stem cells]] has been proposed as a tool for studying the syndrome<ref name="Brigg2013">{{cite journal | vauthors = Briggs JA, Mason EA, Ovchinnikov DA, Wells CA, Wolvetang EJ | title = Concise review: new paradigms for Down syndrome research using induced pluripotent stem cells: tackling complex human genetic disease | journal = Stem Cells Translational Medicine | volume = 2 | issue = 3 | pages = 175–184 | date = March 2013 | pmid = 23413375 | pmc = 3659762 | doi = 10.5966/sctm.2012-0117 }}</ref> and as an approach to therapy.<ref>{{cite journal | vauthors = Mole B |title=Researchers turn off Down's syndrome genes |url=https://www.nature.com/news/researchers-turn-off-down-s-syndrome-genes-1.13406 |journal=Nature News |access-date=25 December 2018 |language=en |doi=10.1038/nature.2013.13406|year=2013 |s2cid=87422171 |doi-access=free }}</ref> Other methods being studied include the use of [[antioxidant]]s, [[gamma secretase inhibition]], [[adrenergic agonist]]s, and [[memantine]].<ref>{{cite journal | vauthors = Costa AC, Scott-McKean JJ | title = Prospects for improving brain function in individuals with Down syndrome | journal = CNS Drugs | volume = 27 | issue = 9 | pages = 679–702 | date = September 2013 | pmid = 23821040 | doi = 10.1007/s40263-013-0089-3 | s2cid = 24030020 }}</ref> Research is often carried out on an [[animal model]], the [[mouse models of Down syndrome|Ts65Dn mouse]].<ref>{{cite journal | vauthors = Costa AC | title = On the promise of pharmacotherapies targeted at cognitive and neurodegenerative components of Down syndrome | journal = Developmental Neuroscience | volume = 33 | issue = 5 | pages = 414–427 | year = 2011 | pmid = 21893967 | pmc = 3254040 | doi = 10.1159/000330861 }}</ref>
Some research seeks to develop appropriate screening tools to determine appropriate treatment strategies should they prove successful.<ref>{{cite journal | vauthors = Goodman MJ, Brixner DI | title = New therapies for treating Down syndrome require quality of life measurement | journal = American Journal of Medical Genetics. Part A | volume = 161A | issue = 4 | pages = 639–641 | date = April 2013 | pmid = 23495233 | doi = 10.1002/ajmg.a.35705 | s2cid = 43840950 | doi-access = free }}</ref>

==Other hominids==
Down syndrome may also occur in [[hominidae|hominids]] other than humans. In [[great apes]] chromosome 22 corresponds to the human chromosome 21{{efn|Using the traditional numbering; the current numbering scheme retains human chromosome numbers, using 2A and 2B instead of 2 and 3 to refer to the two chromosomes that fused into [[chromosome 2]] in humans.<ref>{{cite journal | vauthors = Sansom C | title = The evolution of human chromosome 2. | journal = The Biochemist | date = October 2015 | volume = 37 | issue = 5 | pages = 40–41 | doi = 10.1042/BIO03705040 | url = https://portlandpress.com/biochemist/article-pdf/37/5/40/3805/bio037050040.pdf }}</ref>}} and thus trisomy 22 causes Down syndrome in apes. The condition was observed in a [[common chimpanzee]] in 1969 and a [[Bornean orangutan]] in 1979, but neither lived very long. The common chimpanzee Kanako, born around 1993 in Japan, was genetically tested and found to have chimpanzee trisomy 22 in 2011.  Kanako has some of the same symptoms that are common in human Down syndrome. It is unknown how common this condition is in chimps, but it is plausible it could be roughly as common as Down syndrome is in humans.<ref>{{cite journal | vauthors = Hirata S, Hirai H, Nogami E, Morimura N, Udono T | title = Chimpanzee Down syndrome: a case study of trisomy 22 in a captive chimpanzee | journal = Primates; Journal of Primatology | volume = 58 | issue = 2 | pages = 267–273 | date = April 2017 | pmid = 28220267 | doi = 10.1007/s10329-017-0597-8 | publisher = Springer | hdl-access = free | lccn = sf80001417 | hdl = 2433/228259 | s2cid = 5536021 | oclc = 51531954 | eissn = 1610-7365 }}</ref><ref>{{cite web | vauthors = Hays B |title=Second case of 'Down syndrome' in chimpanzees identified in Japan |url=https://www.upi.com/Second-case-of-Down-syndrome-in-chimpanzees-identified-in-Japan/3991487709938/ |website=UPI |access-date=11 May 2019}}</ref> Kanako was blind, relatively small, and targeted by aggressive group mates. Kanako died in the Kumamoto Sanctuary at [[Kyoto University]] in 2020.<ref>{{Cite journal |last=Hirata |first=Satoshi |date=September 2020 |title=Chimpanzee Kanako |url=https://link.springer.com/10.1007/s10329-020-00856-9 |journal=Primates |language=en |volume=61 |issue=5 |pages=635–638 |doi=10.1007/s10329-020-00856-9 |pmid=32844335 |issn=0032-8332}}</ref>

Fossilized remains of a [[Neanderthal]] aged approximately 6 at death were described in 2024. The child, nicknamed Tina, suffered from a malformation of the inner ear that only occurs in people with Down syndrome, and would have caused hearing loss and disabling [[vertigo]]. The fact that a Neanderthal with such a condition survived to such an age was taken as evidence of compassion and extra-maternal care among Neanderthals.<ref>{{Cite journal|last1=Conde-Valverde |first1=M. |last2=Quirós-Sánchez |first2=A. |last3=Diez-Valero |first3=J. |last4=Mata-Castro |first4=N. |last5=García-Fernández |first5=A. |last6=Quam |first6=R. |last7=Carretero |first7=J. M. |last8=García-González |first8=R. |last9=Rodríguez |first9=L. |last10=Sánchez-Andrés |first10=Á. |last11=Arsuaga |first11=J. L. |last12=Martínez |first12=I. |last13=Villaverde |first13=V. |title=The child who lived: Down syndrome among Neanderthals? |year=2024 |journal=Science Advances |volume=10 |issue=26 |article-number=eadn9310 |doi=10.1126/sciadv.adn9310 |pmid=38924400 |doi-access=free |pmc=11204207 |bibcode=2024SciA...10N9310C }}</ref><ref name=neanderthal>{{cite web|url=https://phys.org/news/2024-06-case-syndrome-neanderthals-documented.html|title=First case of Down syndrome in Neanderthals documented in new study}}</ref>

==In popular culture==
[[File:Chris_Burke.jpg|thumb | [[Chris Burke (actor)|Chris Burke]], an actor with Down syndrome, born in 1965]]

===Individuals===
*[[Jamie Brewer]] is an American actress and model. She is best known for her roles in the [[FX (TV channel)|FX]] horror anthology television series ''[[American Horror Story]]''.<ref>{{Cite news | vauthors = Lawton A |date=2011-11-21 |title=Interview with Jamie Brewer |url=https://mediamikes.com/2011/11/interview-with-jamie-brewer/ |access-date=2023-04-01 |website=MediaMikes |language=en-US}}</ref> In its first season, ''[[American Horror Story: Murder House|Murder House]]'', she portrayed [[Adelaide Langdon|Adelaide "Addie" Langdon]]; in the third season, ''[[American Horror Story: Coven|Coven]]'', she portrayed [[Nan (American Horror Story)|Nan]], an enigmatic and [[clairvoyant]] [[witch]]; in the fourth season ''[[American Horror Story: Freak Show|Freak Show]]'', she portrayed Chester Creb's vision of his doll, Marjorie; in the seventh season ''[[American Horror Story: Cult|Cult]]'', she portrayed Hedda, a member of the 'SCUM' crew, led by feminist [[Valerie Solanas]]; and she also returned to her role as Nan in the eighth season, ''[[American Horror Story: Apocalypse|Apocalypse]]''. In February 2015, Brewer became the first woman with Down syndrome to walk the red carpet at [[New York Fashion Week]], for designer Carrie Hammer.<ref>{{Cite web | vauthors = Probus S, McNeal J |title=Meet The First Woman With Down Syndrome To Walk At Fashion Week |url=https://www.buzzfeednews.com/article/stephaniemcneal/meet-the-first-woman-with-down-syndrome-to-walk-at-fashion-w |access-date=2023-04-01 |website=BuzzFeed News |date=12 February 2015 |language=en}}</ref>
*[[Tommy Jessop]] is a British actor, author and activist. He starred in the [[BAFTA]]-nominated dramas ''[[Coming Down the Mountain]]'' and ''[[Line of Duty]]'',<ref name="Independent Feature">{{cite news| url=https://www.independent.co.uk/news/media/mark-haddon-first-he-tackled-aspergers-now-the-writer-is-putting-downs-syndrome-in-the-spotlight-with-a-new-drama-463565.html | location=London | work=The Independent | first=James | last=Rampton | title=Mark Haddon: First he tackled Asperger's, now the writer is putting Down's syndrome in the spotlight with a new drama | date=30 August 2007}}</ref><ref>{{Cite web|last=Griffiths|first=Eleanor Bley|date=21 March 2021|title=Who is Terry Boyle? Line of Duty season 6 brings back a familiar character|url=https://www.radiotimes.com/tv/drama/line-of-duty-terry-boyle/|access-date=22 March 2021|website=[[Radio Times]]}}</ref> and was the first person with Down syndrome to play [[Hamlet]] professionally as part of a touring production with [[Blue Apple Theatre]].<ref name="This Is Cornwall">{{cite web |url=http://www.thisiscornwall.co.uk/s-actor-tackles-Hamlet/story-15991047-detail/story.html |title=Down's actor tackles Hamlet &#124; This is Cornwall |access-date=23 February 2013 |archive-url=https://web.archive.org/web/20130411202311/http://www.thisiscornwall.co.uk/s-actor-tackles-Hamlet/story-15991047-detail/story.html |archive-date=11 April 2013 }}</ref> Jessop is a prominent campaigner in the UK and was a key figure in the creation of the [[Down Syndrome Act 2022]].<ref name="Campaign Work">{{cite web|url=https://www.telegraph.co.uk/tv/2023/06/29/tommy-jessop-downs-syndrome-line-of-duty/|title=tommy-jessop-downs-syndrome-line-of-duty|website=Telegraph|date=29 June 2023 }}</ref> In 2023 [[Headline Publishing Group]] published Jessop's autobiography ''A Life Worth Living: Acting, Activism and Everything Else''.<ref>{{Cite web |date=2023-06-27 |title=Award-winning Hampshire actor releases memoir on life with Down Syndrome |url=https://www.hampshirechronicle.co.uk/news/23612779.winchesters-tommy-jessop-releases-memoir-life-syndrome/ |access-date=2023-08-10 |website=Hampshire Chronicle |language=en}}</ref>  
*[[Sofía Jirau]] is a [[Puerto Ricans|Puerto Rican]] model with Down syndrome, working with designers and media outlets such as Vogue Mexico, People, and Hola!.<ref>{{Cite web |date=2020-02-19 |title=Puerto Rican model with Down Syndrome, Sofía Jirau is conquering the fashion world |url=https://www.hola.com/us/fashion/20211021325691/puerto-rican-model-down-syndrome-sofia-jirau/ |access-date=2023-04-01 |website=HOLA |language=en-US}}</ref><ref>{{Cite web | vauthors = Mier T | date = 17 February 2020 |title=NYFW: Model with Down Syndrome Says 'There Are No Limits' |url=https://people.com/human-interest/latina-model-with-down-syndrome-stuns-at-nyfw/ |access-date=2023-04-01 |website=Peoplemag |language=en}}</ref><ref>{{Cite web |date=2020-02-13 |title=Sofía Jirau, la modelo latina con síndrome de down que decantó en el Fashion Week de Nueva York |url=https://www.vogue.mx/moda/articulo/sofia-jirau-la-modelo-puertorriquena-con-sindrome-de-down-en-el-fashion-week-de-nueva-york |access-date=2023-04-01 |website=Vogue |language=es-MX}}</ref> In February 2020, Jirau made her debut at [[New York Fashion Week]].<ref>{{Cite web |last=V |first=Juliette |title=Latina Model With Down Syndrome Walks at New York Fashion Week |url=https://themighty.com/topic/down-syndrome/sofia-jirau-down-syndrome-model-new-york-fashion-week/ |access-date=2023-04-01 |website=The Mighty |language=en}}</ref> Then in February 2022, she became the first-ever model with Down Syndrome to be hired by the American retail company [[Victoria's Secret]].<ref>{{Cite web | vauthors = Holender S |date=2022-02-17 |title=Meet Sofia Jirau, Victoria's Secret's 1st Model With Down Syndrome |url=https://www.usmagazine.com/stylish/news/sofia-jirau-is-victorias-secrets-1st-model-with-down-syndrome/ |access-date=2023-04-01 |website=Us Weekly |language=en-US}}</ref> She walked the [[Los Angeles Fashion Week|LA Fashion Week]] runway in 2022.<ref name="About me">{{Cite web |title=About me |url=https://www.sofiajirau.com/en/quien-soy |access-date=2023-04-01 |website=Sofia Jirau Model |language=en}}</ref> Jirau launched a campaign in 2021 called Sin Límites or No Limits "which seeks to make visible the challenges facing the Down syndrome community, demonstrate our ability to achieve our goals, and raise awareness about the condition throughout the world."<ref name="About me" />
*[[Chris Nikic]] is the first person with Down syndrome to finish an [[Ironman Triathlon]].<ref>{{Cite news |title=Nikic becomes first person with Down's syndrome to finish Ironman |language=en-GB |work=BBC Sport |url=https://www.bbc.com/sport/triathlon/54869998 |access-date=2023-04-01}}</ref> He was awarded the [[Jimmy V Award|Jimmy V Award for Perseverance]] at the [[2021 ESPY Awards]].<ref>{{Cite web |date=2021-07-10 |title=2021 ESPYS award winners |url=https://www.espn.com/espys/story/_/page/voting-winners/2021-espys-award-winners |access-date=2023-04-01 |website=ESPN.com |language=en}}</ref> Nikic continues to run races around the world, using his platform to promote his 1% Better message and bring awareness to the endless possibilities for people with Down syndrome.<ref>{{Cite web |title=About – Chris Nikic |url=https://chrisnikic.com/about/ |access-date=2023-04-01 |language=en-US | work = chrisnikic.com }}</ref>
*[[Grace Strobel]] is an American model and the first person with Down Syndrome to represent an American skin-care brand.<ref>{{Cite web | vauthors = Abelman D | date = 21 March 2021 |title=Grace Strobel Knows How Good Her Skin Looks |url=https://www.allure.com/story/grace-strobel-obagi-skin-care-routine-interview |access-date=2023-04-01 |website=Allure |language=en-US}}</ref> She first joined Obagi in 2020, and continues to be an Ambassador for the brand as of 2022.<ref>{{Cite press release |last=Obagi |title=Obagi Announces Partnership with Down Syndrome Advocate, Grace Strobel, as new SKINCLUSION Ambassador and Face of New Obagi Clinical Cleanser |url=https://www.prnewswire.com/news-releases/obagi-announces-partnership-with-down-syndrome-advocate-grace-strobel-as-new-skinclusion-ambassador-and-face-of-new-obagi-clinical-cleanser-301143570.html |access-date=2023-04-01 |website=www.prnewswire.com |language=en}}</ref><ref>{{Cite press release |last=Obagi |title=Obagi Clinical® Continues Collaboration with Down Syndrome Advocate Grace Strobel |url=https://www.prnewswire.com/news-releases/obagi-clinical-continues-collaboration-with-down-syndrome-advocate-grace-strobel-301532656.html |access-date=2023-04-01 |website=www.prnewswire.com |language=en}}</ref> She walked the runway representing [[Tommy Hilfiger (company)|Tommy Hilfiger]] for Runway of Dreams [[New York Fashion Week]] 2020 and [[Atlantic City Fashion Week]].<ref name="At just 25 years old, Chesterfield native Grace Strobel continues to shatter stereotypes, shift societal expectations and make history.">{{Cite web | vauthors = LeBlanc DA |title=The Grace Effect: Local model is on a mission to change the world in style |url=https://www.westnewsmagazine.com/lifestyles/the-grace-effect-local-model-is-on-a-mission-to-change-the-world-in-style/article_af990822-99d2-11ec-a659-6fef10246f05.html |access-date=2023-04-01 |website=WestNewsMagazine.com |date=March 2022 |language=en}}</ref> Strobel has been featured in ''[[Forbes]]'', on [[Today (American TV program)|''The Today Show'']], ''[[Good Morning America]]'', by [[Rihanna]]'s [[Fenty Beauty]], Lady Gaga's Kindness Channel, and many more.<ref name="At just 25 years old, Chesterfield native Grace Strobel continues to shatter stereotypes, shift societal expectations and make history." /><ref name="The Grace Effect" /> She is also a public speaker and gives a presentation called #TheGraceEffect about what it is like to live with Down syndrome.<ref>{{Cite web |title=Down syndrome advocate Grace Strobel on pushing boundaries: 'Let no one tell you what you can and cannot achieve' |url=https://www.yahoo.com/lifestyle/down-syndrome-advocate-grace-strobel-on-pushing-boundaries-201717691.html |access-date=2023-04-01 |website=Yahoo Life |date=21 March 2022 |language=en-US}}</ref><ref name="The Grace Effect">{{Cite web | vauthors = Strobel G |date=2020-01-24 |title=#TheGraceEffect – Creating Ripples With Kindness And Respect |url=https://www.channelkindness.org/the-grace-effect/ |access-date=2023-04-01 |website=Channel Kindness |language=en-US}}</ref>

===Television and film===
*''[[Life Goes On (TV series)|Life Goes On]]'' is an American drama television series that aired on [[American Broadcasting Company|ABC]] from September 12, 1989, to May 23, 1993.<ref>{{Citation |title=Life Goes On (TV Series 1989–1993) - IMDb |url=https://www.imdb.com/title/tt0096635/ |access-date=2023-04-01 |language=en-US}}</ref> The show centers on the Thatcher family living in [[Chicago metropolitan area|suburban Chicago]]: Drew, his wife Libby, and their children Paige, Rebecca and Charles. Charles, called Corky on the show and portrayed by [[Chris Burke (actor)|Chris Burke]], was the first major character on a television series with Down syndrome.<ref>{{Cite web |title=Life Goes On Actor Chris Burke on Being the First Primetime Television Star with Down Syndrome |url=https://www.oprah.com/own-where-are-they-now/chris-burke-the-first-primetime-star-with-down-syndrome-video | archive-url = https://web.archive.org/web/20150814072752/https://www.oprah.com/own-where-are-they-now/chris-burke-the-first-primetime-star-with-down-syndrome-video | archive-date = 14 August 2015 |access-date=2023-04-01 |website=Oprah.com}}</ref> Burke's revolutionary role conveyed a realistic portrayal of people with Down syndrome and changed the way audiences viewed people with disabilities.<ref>{{Cite web |last1=Randle N |date=1990-12-20 |title='Our Ticket to Acceptance': Actor With Down's Syndrome on 'Life Goes On' Has Become Role Model for Many |url=https://www.latimes.com/archives/la-xpm-1990-12-20-ca-9447-story.html |access-date=2023-04-01 |website=Los Angeles Times |language=en-US}}</ref>
*[[Champions (2023 film)|''Champions'']] (2023) is a film starring four main actors with Down syndrome: [[Madison Tevlin]], Kevin Iannucci, Matthew Von Der Ahe and James Day Keith.<ref>{{Citation |title=Champions (2023) - IMDb |url=https://www.imdb.com/title/tt15339570/ |access-date=2023-04-01 |language=en-US}}</ref> It is an American [[Sports film|sports]] [[Comedy film|comedy]] film directed by [[Bobby Farrelly]] in his [[List of directorial debuts|solo directorial debut]], from a screenplay written by Mark Rizzo. The film stars [[Woody Harrelson]] as a temperamental [[NBA G League|minor-league basketball]] coach who after an arrest must coach a team of players with intellectual disabilities as community service; [[Kaitlin Olson]], [[Ernie Hudson]], and [[Cheech Marin]] also star.
*[[Born This Way (TV series)|''Born This Way'']] is an [[Television in the United States|American]] [[reality television]] series produced by [[Bunim/Murray Productions]] featuring seven adults with Down syndrome with work hard to achieve goals and overcome obstacles.<ref>{{Cite web |title=Born This Way |url=https://www.emmys.com/shows/born-way |access-date=2023-04-01 |website=Television Academy |language=en}}</ref> The show received a Television Academy Honor in 2016.<ref>{{Cite web | vauthors = Heasley S |date=2015-11-16 |title=New TV Series Features Young Adults With Down Syndrome |url=https://www.disabilityscoop.com/2015/11/16/new-tv-series-down-syndrome/20963/ |access-date=2023-04-01 |website=Disability Scoop |language=en}}</ref>
*''[[The Peanut Butter Falcon]]'' is a 2019 American [[comedy-drama]] film written and directed by Tyler Nilson and Michael Schwartz, in their directorial film debut, and starring [[Zack Gottsagen]], [[Shia LaBeouf]], [[Dakota Johnson]] and [[John Hawkes (actor)|John Hawkes]].<ref>{{Citation |title=The Peanut Butter Falcon (2019) - IMDb |url=https://www.imdb.com/title/tt4364194/ |access-date=2023-04-01 |language=en-US}}</ref> The plot follows a young man with Down syndrome who escapes from an [[Assisted living|assisted living facility]], in order to follow his dream of being a wrestler, and befriends a wayward fisherman on the run. As the two men form a rapid bond, a [[social work]]er attempts to track them.<ref>{{Cite web |title=The Peanut Butter Falcon |url=https://www.lionsgate.com/movies/the-peanut-butter-falcon |access-date=1 April 2023 |website=Lionsgate}}</ref>

===Music===
*The [[Devo]] song "[[Mongoloid (song)|Mongoloid]]" is about someone with Down syndrome.
*The [[Amateur Transplants]] song "[[Fitness to Practice|Your Baby]]" is about a fetus with Down syndrome.

===Toys===
*In 2023, [[Mattel]] released a [[Barbie]] doll with characteristics of a person having Down syndrome as a way to promote diversity.<ref>{{cite news | url=https://www.theguardian.com/society/2023/apr/25/barbie-doll-with-downs-syndrome-launched-by-mattel | title=Barbie doll with Down's syndrome launched by Mattel | newspaper=The Guardian | date=25 April 2023 | last1=Marsh | first1=Sarah }}</ref>

== See also ==
* [[List of syndromes]]
* [[Characteristics of syndromic ASD conditions]]

== Notes ==
{{notelist}}

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin}}
* {{Cite news |vauthors=Fox N |date=2021-11-26 |title='World-leading' Down's syndrome bill clears first hurdle in Parliament |url=https://www.bbc.com/news/uk-politics-59432487 |url-status=live |archive-url=https://web.archive.org/web/20211127155428/https://www.bbc.com/news/uk-politics-59432487 |archive-date= 2021-11-27 |language=en-GB |publisher=[[BBC News]] |access-date=2021-11-27}}
* {{Cite journal |vauthors=Thompson SB |date=1999 |title=Examining dementia in Down's syndrome (DS): decline in social abilities in DS compared with other learning disabilities |journal=Clinical Gerontologist |volume=20 |issue=3 |pages=23–44 |publisher=Taylor & Francis (Routledge) |doi=10.1300/j018v20n03_04 |issn=1545-2301 |oclc=1106716083 }}
* {{Cite journal |vauthors=Thompson SB |date=2000a<!-- The "a" and "b" are for convenience—I do not actually know the order of publication. --> |title=The Central Executive System in people with Down's syndrome and dementia |journal=Clinical Gerontologist |volume=21 |issue=3 |pages=3–32 |publisher=Taylor & Francis (Routledge) |doi=10.1300/j018v21n03_02 |issn=1545-2301 |oclc=1106716083 |s2cid=218575706 }}
* {{Cite journal |vauthors=Thompson SB |date=2000b<!-- The "a" and "b" are for convenience—I do not actually know the order of publication. --> |title=Investigation into Down's syndrome and dementia |journal=Journal of the Association of Practitioners in Learning Disability |volume=17 |issue=3 |pages=10–14 }}
{{Refend}}

== External links ==
{{sister project links|d=Q47715|c=Category:Down syndrome|n=no|b=no|v=no|voy=no|m=no|mw=no|s=no|wikt=no|species=no}}
* [https://www.nhs.uk/conditions/downs-syndrome/ Down's syndrome] by the UK [[National Health Service]]

{{Medical condition classification and resources
| ICD11 = {{ICD11|LD40.0}}
| ICD10 = {{ICD10|Q90}}
| ICD9 = {{ICD9|758.0}}
| ICDO = 
| OMIM = 190685
| OMIM_mult = 
| MedlinePlus = 000997
| eMedicineSubj = ped
| eMedicineTopic = 615
| DiseasesDB = 3898
| MeshID = D004314
}}

{{Autism spectrum}}
{{Chromosomal abnormalities |state=collapsed}}
{{Disability navbox|state=collapsed}}
{{Authority control}}

[[Category:Down syndrome| ]]
[[Category:Autosomal trisomies]]
[[Category:Genetic syndromes]]
[[Category:Syndromes with intellectual disability]]
[[Category:Wikipedia medicine articles ready to translate (full)]]
[[Category:Syndromes affecting the gastrointestinal tract]]
[[Category:Syndromes affecting the heart]]
[[Category:Syndromes affecting the nervous system]]
[[Category:Syndromes with craniofacial abnormalities]]
[[Category:Syndromic autism]]
[[Category:Diseases named after discoverers]]