Editing Down syndrome (section)

==Cause==
{{Main|Genetics of Down syndrome}}The cause of the extra full or partial chromosome is still unknown.<ref name=":0" /> Most of the time, Down syndrome is caused by a random mistake in cell division during early development of the fetus, but not inherited,<ref name=":1">{{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> and 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]]]]
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/>

The extra chromosome content can arise through several different ways. 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===
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>

=== 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=":0">{{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>

===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>