Down syndrome

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>Template:Cite journal</ref> It is usually associated with developmental delays, mild to moderate intellectual disability, and characteristic physical features.<ref name="Wei2010">Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The parents of the affected individual are usually genetically normal.<ref name=Steph2010>Template:Cite book</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Usually, babies get 23 chromosomes from each parent for a total of 46, whereas in Down syndrome, a third 21st chromosome is attached.<ref name="www.intellectualdisability.info">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The extra chromosome is provided at conception as the egg and sperm combine.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="www.intellectualdisability.info" /> Translocation Down syndrome is another rare type.<ref name="CDC" /><ref name="NDDS-about">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Since the introduction of screening, Down syndrome pregnancies are often aborted (rates varying from 50 to 85% depending on maternal age, gestational age, and maternal race/ethnicity).<ref>Template:Cite journal</ref><ref name=Nat2012>Template:Cite journal</ref><ref name=Mans1999>Template:Cite journal</ref>

There is no cure for Down syndrome.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Education and proper care have been shown to provide better quality of life.<ref name=Roi2003>Template:Cite journal</ref> Some children with Down syndrome are educated in typical school classes, while others require more specialized education.<ref name=NADS/> Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education.<ref name=Stein2011>Template:Cite book</ref> In adulthood, about 20% in the United States do some paid work,<ref name=US2013>Template:Cite news</ref> with many requiring a sheltered work environment.<ref name=NADS>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Caretaker support in financial and legal matters is often needed.<ref name=Nelson2011/> Life expectancy is around 50 to 60 years in the developed world, with proper health care.<ref name=Malt2013/><ref name=Nelson2011>Template:Cite book</ref> Regular screening for health issues common in Down syndrome is recommended throughout the person's life.<ref name="Malt2013">Template:Cite journal</ref>

Down syndrome is the most common chromosomal abnormality,<ref name="Martínez-Espinosa">Template:Cite journal</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>Template:Cite journal</ref><ref name=GBD2015De>Template:Cite journal</ref><ref name="GDB2013">Template:Cite journal</ref> The syndrome is named after British physician John Langdon Down, who dedicated his medical practice to the cause.<ref name=Hick2012>Template:Cite journal</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>Template:Cite book</ref> The genetic cause was discovered in 1959.<ref name=Hick2012/> Template:TOC limit

Signs and symptoms

File:Autism somali Center 01.jpg

A boy from Somalia with Down syndrome

Those with Down syndrome nearly always have physical and intellectual disabilities.<ref>Template:Cite book</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>Template:Cite journal</ref> They can have 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 diseases.<ref name=Hick2012/>

Characteristics	Percentage	Characteristics	Percentage
Mental impairment	99%<ref>Template:Cite book</ref>	Abnormal teeth	60%<ref name=Eps2007>Template:Cite book</ref>
Stunted growth	90%<ref>Template:Cite book</ref>	Slanted eyes	60%<ref name=Steph2010/>
Umbilical hernia	90%<ref>Template:Cite book</ref>	Shortened hands	60%<ref name=Eps2007/>
Increased skin on back of neck	80%<ref name=Hick2012/>	Short neck	60%<ref name=Eps2007/>
Low muscle tone	80%<ref name=Dom2007>Template:Cite book</ref>	Obstructive sleep apnea	60%<ref name=Hick2012/>
Narrow roof of mouth	76%<ref name=Eps2007/>	Bent fifth finger tip	57%<ref name=Steph2010/>
Flat head	75%<ref name=Steph2010/>	Brushfield spots in the iris	56%<ref name=Steph2010/>
Flexible ligaments	75%<ref name=Steph2010/>	Single transverse palmar crease	53%<ref name=Steph2010/>
Proportionally large tongue<ref name=Perk2009>Template:Cite journal</ref>	75%<ref name=Dom2007/>	Protruding tongue	47%<ref name=Eps2007/>
Abnormal 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>Template:Cite book</ref>

Physical

File:Feet of a boy with Down Syndrome.JPG

Feet of a boy with Down syndrome, showing the deviated first toes

People with Down syndrome may have these physical characteristics: a small chin, epicanthic folds, 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>Template:Cite book</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 big toe and second toe, a 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>Template:Cite journal</ref> Atlantoaxial instability may cause myelopathy due to cervical spinal cord compression later in life, this often manifests as new onset weakness, problems with coordination, bowel or bladder incontinence, and gait dysfunction.<ref name="Bull 2020">Template:Cite journal</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 Template:Convert, and for women is Template:Convert.<ref>Template:Cite book</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>Template:Cite journal</ref> Growth charts 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

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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Walking is acquired in 50% of children after 24 months.<ref>Template:Cite journal</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>Template:Cite journal</ref> Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that.<ref>Template:Cite book</ref> As they age, the gap tends to widen between people with Down syndrome and their same-age peers.<ref name=Reil2012/><ref>Template:Cite journal</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>Template:Cite journal</ref> 10–45% of those with Down syndrome have either a stutter or rapid and irregular speech, making it difficult to understand them.<ref>Template:Cite journal</ref> After reaching 30 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 occurring in 5–10%.<ref name=Nelson2011/> People with Down syndrome experience a wide range of emotions.<ref>Template:Cite book</ref> While people with Down syndrome are generally happy,<ref>Template:Cite book</ref> symptoms of depression and 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>Template:Cite book</ref> In those who reach 60 years of age, 50–70% have the disease.<ref name="Malt2013"/>

Down syndrome regression disorder is a sudden regression with neuropsychiatric symptoms such as catatonia, possibly caused by an autoimmune disease.<ref>Template:Cite journal</ref> It primarily appears in teenagers and younger adults.<ref>Template:Cite book</ref>

Senses

File:Brushfield eye crop.jpg

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/>

Ocular findings

Brushfield spots (small white or grayish/brown spots on the periphery of the iris), upward slanting palpebral fissures (the opening between the upper and lower lids) and 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">Template:Cite journal</ref><ref name="eyewiki.org">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> especially in the Western World.<ref name="eyewiki.org"/> None of these requires treatment.Template:Citation needed

Visually significant congenital cataracts (clouding of the lens of the eye) occur more frequently with Down syndrome.<ref name="eyewiki.org"/> 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">Template:Cite journal</ref> Dot-like opacities in the cortex of the 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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), 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 (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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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" /> Cataracts occur in 15%,<ref name="Nelson20112">Template:Cite book</ref> and may be present at birth.<ref name="Wei20102" /> Keratoconus may occur in as many as 21–30%.<ref name="eyewiki.org" />

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 ear infections which occur in 40–60%.<ref>Template:Cite book</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>Template:Cite book</ref> Excessive 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>Template:Cite book</ref> Age-related hearing loss of the 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">Template:Cite journal</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>Template:Cite book</ref> People with Down syndrome have a lower risk of hardening of the arteries.<ref name=Malt2013/>

Cancer

Although the overall risk of cancer in Down syndrome is not changed,<ref name=UrbanoP129>Template:Cite book</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 cells 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>Template:Cite journal</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 megakaryoblasts, the precursors cells to megakaryocytes which form blood platelets.<ref name="pmid22867885">Template:Cite journal</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">Template:Cite journal</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>Template:Cite journal</ref>

Myeloid leukemia typically precedes Down syndrome and is accompanied by a condition known as transient abnormal myelopoiesis (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes.<ref name="The paradox of Myeloid Leukemia ass">Template:Cite journal</ref> In Down syndrome, AMKL is typically preceded by transient myeloproliferative disease (TMD), a disorder of 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">Template:Cite journal</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>Template:Cite journal</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">Template:Cite journal</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 genes present on chromosome 21.<ref>Template:Cite book</ref><ref name=Nix2018>Template:Cite journal</ref> One exception is testicular 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/> 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>Template:Cite journal</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 nerve cells controlling the colon.<ref>Template:Cite journal</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 disease, necrotising ulcerative gingivitis, and early tooth loss, especially in the lower front teeth.<ref name="Churchill">Template:Cite book</ref><ref name="Carranza">Template:Cite book</ref> While 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">Template:Cite book</ref> The weakened immune system also contributes to increased incidence of 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">Template:Cite book</ref> less effective oral hygiene habits, and higher plaque indexes.<ref name="Churchill"/><ref name="Mosby"/><ref name="ReferenceA"/><ref name="Saunders">Template:Cite book</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>Template:Cite journal</ref><ref>Template:Cite journal</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 sperm development; however, it may also be related to not being sexually active.<ref name=Prad2006>Template:Cite journal</ref> Without 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

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Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two.<ref name=Patt2009/><ref name="Lana2011">Template:Cite journal</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 karyotypes.<ref name=Nel2010/>

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>Template:Cite news</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.<ref name="Ramasamy">Template:Cite journal</ref>

File:Down Syndrome Karyotype.png

Karyotype for Down syndrome (trisomy 21) showing the three copies of chromosome 21

The extra chromosome content can affect all cells or only some. 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 1–2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down syndrome.<ref name=Nel2010/><ref>Template:Cite book</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 long arms of a chromosome separate together rather than the long and short arm separating together during egg or sperm development.<ref name=Rubin2013>Template:Cite book</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>Template:Cite book</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>Template:Cite book</ref>

Mosaic Down syndrome

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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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.<ref name=Mich2013/> In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q).<ref name=Mich2013>Template:Cite book</ref><ref>Template:Cite book</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>Template:Cite book</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>Template:Cite book</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene.<ref>Template:Cite book</ref> Other research, however, has not confirmed these findings.<ref name=Lana2011/> MicroRNAs are also proposed to be involved.<ref>Template:Cite journal</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>Template:Cite journal</ref> Senile plaques and neurofibrillary tangles are present in nearly all by 35 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 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">Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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, large ventricles, nuchal fold thickness, and an abnormal right subclavian artery, among others.<ref name=Aga2013>Template:Cite journal</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>Template:Cite journal</ref>

• T21.JPG

  Ultrasound of fetus with Down syndrome showing a 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

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>Template:Cite journal</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>Template:Cite journal</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>Template:Cite journal</ref>

Combinations

First- and second-trimester screening<ref name=ACOG2007>Template:Cite journal</ref>

Screen	Week of pregnancy when performed	Detection rate	False positive	Description
Combined test	10–13.5 wks	82–87%	5%	Uses ultrasound to measure nuchal translucency in addition to blood tests for free or total beta-hCG and PAPP-A
Quad screen	15–20 wks	81%	5%	Measures the maternal serum alpha-fetoprotein, unconjugated estriol, hCG, and inhibin-A
Integrated test	15–20 wks	94–96%	5%	Is a combination of the quad screen, PAPP-A, and NT
Cell-free fetal DNA	citation	CitationClass=web }}</ref>	96–100%<ref name="Mersy 318–29">Template:Cite journal</ref>	0.3%<ref>Template:Cite journal</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>Template:Cite journal</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>Template:Cite journal</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

CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite journal</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 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Education and proper care can provide a positive quality of life.<ref name=Roi2003/> Typical childhood vaccinations are recommended.<ref name=Hick2012/>

Health screening

Recommended screening

Testing	Children<ref name=Bull2011>Template:Cite journal</ref>	Adults<ref name=Malt2013/>
Hearing	6 months, 12 months, then yearly	3–5 years
T4 and 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, or earlier if symptoms occur
Sleep study	3 to 4 years, or earlier if symptoms 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 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 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

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 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">Template:Cite journal</ref> Behavioral issues and mental illness are typically managed with counseling or medications.<ref name="Nelson2011" />

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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite book</ref>

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>Template:Cite news</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Other

Tympanostomy tubes are often needed<ref name=Hick2012/> and often more than one set during the person's childhood.<ref name=Rod2012>Template:Cite journal</ref> Tonsillectomy is also often done to help with sleep apnea and 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>Template:Cite journal</ref> donepezil,<ref>Template:Cite journal</ref> rivastigmine,<ref>Template:Cite journal</ref> or galantamine.<ref>Template:Cite journal</ref>

Prognosis

{{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= Template:Ambox

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File:Downs syndrome world map-Deaths per million persons-WHO2012.svg

Deaths due to Down syndrome per million persons in 2012 Template:Div colTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate: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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In Sweden, however, less than 1% have regular jobs.<ref name="EU2006">{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite book</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 problems, the life expectancy has increased.<ref name=Wei2010/> This increase has been from 12 years in 1912,<ref name="Urbano2010108">Template:Cite book</ref> to 25 years in the 1980s,<ref name=Wei2010/> to 50 to 60 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 years and 50% survived to at least 30 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 years and 80% survived to at least 30 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The National Down Syndrome Society provides information regarding raising a child with Down syndrome.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Epidemiology

File:Down risk by maternal age from jk morris.png

The risk of having a Down syndrome pregnancy in relation to a mother's age<ref name=Mor2002>Template:Cite journal</ref>

Down syndrome is the most common chromosomal abnormality in humans.<ref name="Malt2013" /> Globally, Template:As of, Down syndrome occurs in about 1 per 1,000 births<ref name=Wei2010/> and results in about 17,000 deaths.<ref name=Loz2012>Template:Cite journal</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>Template:Cite journal</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>Template:Cite book</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 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 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>Template:Cite book</ref>

History

File:The Adoration of the Christ Child MET DT8852.jpg

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>Template:Cite journal</ref>

File:Portrait of John Langdon Down (c 1870) by Sydney Hodges.jpg

John Langdon Haydon Down — first described Down syndrome

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>Template:Cite journal</ref><ref>Template:Cite book</ref> Édouard Séguin described it as separate from cretinism in 1844.<ref name=Evans2009p12/><ref name="Neri2009">Template:Cite journal</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 Blumenbach's Mongoloid race, John Langdon Down used the term "mongoloid".<ref>Template:Cite book</ref> He felt that the existence of Down syndrome confirmed that all peoples were genetically related.<ref>Template:Cite book</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>Template:Cite book</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">Template:Cite journal</ref> While this terminology continued to be used until the late twentieth century,<ref>Template:Cite book</ref>Template:Rp 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 BC at Poulnabrone dolmen in Ireland.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref> and the 16th-century painting The Adoration of the Christ Child.<ref>Template:Cite book</ref><ref name=Evans2009p1314>Template:Cite book</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. states 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">Template:Cite book</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>Template:Cite book</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>Template:Cite news</ref> The discovery took place in the laboratory of Raymond Turpin at the Hôpital Trousseau in Paris, France.<ref>Template:Cite journal</ref> Jérôme Lejeune and Marthe Gautier were both his students.<ref>Template:Cite journal</ref>

As a result of this discovery, the condition became known as trisomy 21.<ref>Template:Cite book</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>Template:Cite book</ref>

Society and culture

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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite journal</ref> However, both the possessive and nonpossessive forms remain in use by the general population.<ref name=Smith-2011>Template:Cite book</ref> The term "trisomy 21" is also commonly used.<ref name="Rod2011">Template:Cite journal</ref><ref>Template:Cite book</ref>

Ethics

Obstetricians routinely offer antenatal screenings for various conditions, including Down syndrome.<ref name=Cher2010>Template:Cite journal</ref><ref>Template:Cite journal</ref> When results from testing become available, it is considered an ethical requirement to share the results with the patient.<ref name=Cher2010/><ref>Template:Cite journal</ref>

Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being.<ref>Template:Cite journal</ref> One criticism of this reasoning is that it often values those with disabilities less.<ref>Template:Cite journal</ref> Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The disability rights movement does not have a position on screening,<ref name=Paren2003/> although some members consider testing and abortion discriminatory.<ref name=Paren2003>Template:Cite journal</ref> Some in the United States who are anti-abortion support abortion if the fetus is disabled, while others do not.<ref name=Green1997>Template:Cite journal</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 Orthodox Christianity and Roman Catholicism do not.<ref name=Rel2013>Template:Cite book</ref> Women may face disapproval whether they choose abortion or not.<ref>Template:Cite book</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 Second World War.<ref name="Adv2011">Template:Cite book</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 mental hospitals or asylums. Organizations included the Royal Society for Handicapped Children and Adults founded in the UK in 1946 by Judy Fryd,<ref name="Adv2011" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite news</ref>

The first World Down Syndrome Day was held on 21 March 2006.<ref name=WDSD2014>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The day and month were chosen to correspond with 21 and trisomy, respectively.<ref>Template:Cite book</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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 Paralympic Swimming S14 intellectual impairment category (provided they score low in IQ tests), they are often outmatched by the superior physicality of their opponents.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Despite ongoing advocacy, the issue remains unresolved, and swimmers with Down syndrome continue to face challenges in accessing appropriate classification pathways.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Research

Template:See also 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>Template:Cite book</ref> Gene therapy delivered via stem cells has been proposed as a tool for studying the syndrome<ref name="Brigg2013">Template:Cite journal</ref> and as an approach to therapy.<ref>Template:Cite journal</ref> Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonists, and memantine.<ref>Template:Cite journal</ref> Research is often carried out on an animal model, the Ts65Dn mouse.<ref>Template:Cite journal</ref> Some research seeks to develop appropriate screening tools to determine appropriate treatment strategies should they prove successful.<ref>Template:Cite journal</ref>

Other hominids

Down syndrome may also occur in hominids other than humans. In great apes chromosome 22 corresponds to the human chromosome 21Template:Efn 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>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Kanako was blind, relatively small, and targeted by aggressive group mates. Kanako died in the Kumamoto Sanctuary at Kyoto University in 2020.<ref>Template:Cite journal</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>Template:Cite journal</ref><ref name=neanderthal>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In popular culture

File:Chris Burke.jpg

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 horror anthology television series American Horror Story.<ref>Template:Cite news</ref> In its first season, Murder House, she portrayed Adelaide "Addie" Langdon; in the third season, Coven, she portrayed Nan, an enigmatic and clairvoyant witch; in the fourth season Freak Show, she portrayed Chester Creb's vision of his doll, Marjorie; in the seventh season 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, 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>{{#invoke:citation/CS1|citation

|CitationClass=web }}</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">Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2023 Headline Publishing Group published Jessop's autobiography A Life Worth Living: Acting, Activism and Everything Else.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Sofía Jirau is a Puerto Rican model with Down syndrome, working with designers and media outlets such as Vogue Mexico, People, and Hola!.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In February 2020, Jirau made her debut at New York Fashion Week.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> She walked the LA Fashion Week runway in 2022.<ref name="About me">{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite news</ref> He was awarded the Jimmy V Award for Perseverance at the 2021 ESPY Awards.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Grace Strobel is an American model and the first person with Down Syndrome to represent an American skin-care brand.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> She first joined Obagi in 2020, and continues to be an Ambassador for the brand as of 2022.<ref>Template:Cite press release</ref><ref>Template:Cite press release</ref> She walked the runway representing 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.">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Strobel has been featured in Forbes, on 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="The Grace Effect">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Television and film

• Life Goes On is an American drama television series that aired on ABC from September 12, 1989, to May 23, 1993.<ref>Template:Citation</ref> The show centers on the Thatcher family living in suburban Chicago: Drew, his wife Libby, and their children Paige, Rebecca and Charles. Charles, called Corky on the show and portrayed by Chris Burke, was the first major character on a television series with Down syndrome.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> Burke's revolutionary role conveyed a realistic portrayal of people with Down syndrome and changed the way audiences viewed people with disabilities.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Struck by Lightning, an Australian film by Jerzy Domaradzki and starring Garry McDonald, is a comedy-drama depicting the efforts by a newly appointed physical education teacher to introduce soccer to a specialized school for youths with Down syndrome.
• 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>Template:Citation</ref> It is an American sports comedy film directed by Bobby Farrelly in his solo directorial debut, from a screenplay written by Mark Rizzo. The film stars Woody Harrelson as a temperamental 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 is an 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>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> The show received a Television Academy Honor in 2016.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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.<ref>Template:Citation</ref> The plot follows a young man with Down syndrome who escapes from an 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 worker attempts to track them.<ref>{{#invoke:citation/CS1|citation

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Music

• The Devo song "Mongoloid" is about someone with Down syndrome.
• The Amateur Transplants song "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>Template:Cite news</ref>

See also

• List of syndromes
• Characteristics of syndromic ASD conditions

Further reading

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External links

• Down's syndrome by the UK National Health Service