# Down syndrome

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Genetic disorder

Medical condition

Down syndrome Other names Down's syndrome, Down's, trisomy 21 An eight-year-old boy displaying characteristic facial features of Down syndrome Specialty Medical genetics, pediatrics Symptoms Delayed development, characteristic physical features, mild to moderate intellectual disability[1] Usual onset Mostly at conception, rarely after fertilization[2] Duration Lifelong Causes Third copy of chromosome 21[3] Risk factors Older age of mother, prior affected child[4][5] Diagnostic method Prenatal screening, genetic testing[6] Treatment Physical therapy, occupational therapy, speech therapy, educational support, supported work environment[7][8] Prognosis Life expectancy 50 to 60 years (developed world)[9][10] Frequency 5.4 million (0.1%)[1][11] Named after John Langdon Down

**Down syndrome** or **Down's syndrome**,[12] also known as **Trisomy 21**, is a [genetic disorder](/source/Genetic_disorder) caused by the presence of all or part of a third copy of [chromosome 21](/source/Chromosome_21).[3] It is usually associated with [developmental](/source/Child_development) delays, mild to moderate [intellectual disability](/source/Intellectual_disability), and characteristic physical features.[1][13]

The parents of the affected individual are usually [genetically](/source/Genetically) normal.[14] 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.[4] It is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability.[2] Three different genetic forms have been identified. The most common, trisomy 21, involves an extra copy of chromosome 21 in all [cells](/source/Cell_(biology)).[15] The extra chromosome is provided at conception as the egg and sperm combine.[16] [Translocation Down syndrome](/source/Translocation_Down_syndrome) involves attachment of extra chromosome 21 material.[17][18] In 1–2% of cases, the additional chromosome is added in the [embryo](/source/Embryo) stage and only affects some of the cells in the body; this is known as [mosaic Down syndrome](/source/Mosaic_Down_syndrome).[19][15]

Down syndrome can be identified during pregnancy by [prenatal screening](/source/Prenatal_screening), followed by diagnostic testing, or after birth by direct observation and [genetic testing](/source/Genetic_testing).[6] Since the introduction of screening, Down syndrome [pregnancies](/source/Pregnancies) are often [aborted](/source/Abortion) (rates varying from 50 to 85% depending on maternal age, gestational age, and maternal race/ethnicity).[20][21][22]

There is no cure for Down syndrome.[23] Education and proper care have been shown to provide better [quality of life](/source/Quality_of_life).[7] Some children with Down syndrome are educated in typical school classes, while others require more [specialized education](/source/Special_education).[8] Some individuals with Down syndrome graduate from [high school](/source/High_school), and a few attend [post-secondary education](/source/Post-secondary_education).[24] In adulthood, about 20% in the [United States](/source/United_States) do some paid work,[25] with many requiring a [sheltered work environment](/source/Sheltered_workshop).[8] [Caregiver](/source/Caregiver) support in financial and legal matters is often needed.[10] Life expectancy is around 50 to 60 years in the [developed world](/source/Developed_world), with proper [health care](/source/Health_care).[9][10] Regular [screening](/source/Screening_(medicine)) for health issues common in Down syndrome is recommended throughout the person's life.[9]

Down syndrome is the most common [chromosomal abnormality](/source/Chromosomal_abnormality),[26] occurring in about 1 in 1,000 babies born worldwide,[1] and one in 700 in the US.[17] In 2015, there were 5.4 million people with Down syndrome globally, of whom 27,000 died, down from 43,000 deaths in 1990.[11][27][28] The syndrome is named after British physician [John Langdon Down](/source/John_Langdon_Down), who dedicated his medical practice to the cause.[29] Some aspects were described earlier by French psychiatrist [Jean-Étienne Dominique Esquirol](/source/Jean-%C3%89tienne_Dominique_Esquirol) in 1838 and French physician [Édouard Séguin](/source/%C3%89douard_S%C3%A9guin) in 1844.[30] The genetic cause was discovered in 1959.[29]

## Signs and symptoms

A boy with Down syndrome

Those with Down syndrome nearly always have physical and intellectual disabilities.[31] As adults, their mental abilities are typically similar to those of an eight- or nine-year-old.[9] At the same time, their emotional and social awareness is very high.[32] They can have [poor immune function](/source/Immunodeficiency)[14] and generally reach [developmental milestones](/source/Developmental_milestones) at a later age.[10] They have an increased risk of a number of health concerns, such as [congenital heart disease](/source/Congenital_heart_defect), [epilepsy](/source/Epilepsy), [leukemia](/source/Leukemia), and [thyroid diseases](/source/Thyroid_disease).[29]

A man with Down syndrome pictured centre in the photo

Characteristics Percentage Characteristics Percentage Mental impairment 99%[33] Abnormal teeth 60%[34] Stunted growth 90%[35] Slanted eyes 60%[14] Umbilical hernia 90%[36] Shortened hands 60%[34] Increased skin on back of neck 80%[29] Short neck 60%[34] Low muscle tone 80%[37] Obstructive sleep apnea 60%[29] Narrow roof of mouth 76%[34] Bent fifth finger tip 57%[14] Flat head 75%[14] Brushfield spots in the iris 56%[14] Flexible ligaments 75%[14] Single transverse palmar crease 53%[14] Proportionally large tongue[38] 75%[37] Protruding tongue 47%[34] Abnormal outer ears 70%[29] Congenital heart disease 40%[34] Flattened nose 68%[14] Strabismus ≈35%[1] Separation of first and second toes 68%[34] Undescended testicles 20%[39]

### Physical

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

People with Down syndrome may have these physical characteristics: a [small chin](/source/Microgenia), [epicanthic folds](/source/Epicanthic_fold), [low muscle tone](/source/Hypotonia), a flat [nasal bridge](/source/Nasal_bridge), and a protruding tongue. A protruding tongue is caused by low tone and weak facial muscles, and often corrected with myofunctional exercises.[40] Some characteristic airway features can lead to [obstructive sleep apnea](/source/Obstructive_sleep_apnea) in around half of those with Down syndrome.[29] Other common features include: excessive joint flexibility, extra space between [big toe](/source/Hallux) and second toe, a [single crease of the palm](/source/Single_transverse_palmar_crease), and short fingers.[34][37]

Instability of the [atlantoaxial joint](/source/Atlantoaxial_joint) occurs in about 1–2%.[41] Atlantoaxial instability may cause [myelopathy](/source/Myelopathy) due to cervical spinal cord compression later in life, this often manifests as new onset weakness, [problems with co-ordination](/source/Ataxia), bowel or bladder incontinence, and gait dysfunction.[42] 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.[42]

Growth in height is slower, resulting in adults who tend to have [short stature](/source/Short_stature)—the average height for men is 154 centimetres (5 feet 1 inch), and for women is 142 centimetres (4 feet 8 inches).[43] Individuals with Down syndrome are at increased risk for [obesity](/source/Obesity) as they age due to increased risk of [hypothyroidism](/source/Hypothyroidism), other medical issues and lifestyle.[29][44] [Growth charts](/source/Growth_chart) have been developed specifically for children with Down syndrome.[29]

### Neurological

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.[14] 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.[45] Walking is acquired in 50% of children after 24 months.[46]

Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) [intellectual disability](/source/Intellectual_disability) with some cases having severe (IQ: 20–35) difficulties.[1][47] Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that.[48] As they age, the gap tends to widen between people with Down syndrome and their same-age peers.[47][49]

Commonly, individuals with Down syndrome have better language understanding than ability to speak.[29][47] [Babbling](/source/Babbling) typically emerges around 15 months on average.[50] 10–45% of those with Down syndrome have either a [stutter](/source/Stutter) or [rapid and irregular speech](/source/Cluttering), making it difficult to understand them.[51] After reaching 30 years of age, some may lose their ability to speak.[9]

They typically do fairly well with social skills.[29] Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability.[47] In children with Down syndrome, [mental illness](/source/Mental_illness) occurs in nearly 30% with [autism](/source/Autism) occurring in 5–10%.[10] People with Down syndrome experience a wide range of emotions.[52] While people with Down syndrome are generally happy,[53] symptoms of [depression](/source/Depression_(mood)) and [anxiety](/source/Anxiety_(mood)) may develop in early adulthood.[9]

Children and adults with Down syndrome are at increased risk of [epileptic seizures](/source/Epileptic_seizures), which occur in 5–10% of children and up to 50% of adults.[9] This includes an increased risk of a specific type of seizure called [infantile spasms](/source/Infantile_spasms).[29] Many (15%) who live 40 years or longer develop [Alzheimer's disease](/source/Alzheimer's_disease).[54] In those who reach 60 years of age, 50–70% have the disease.[9]

[Down syndrome regression disorder](https://en.wikipedia.org/w/index.php?title=Down_syndrome_regression_disorder&action=edit&redlink=1) is a sudden [regression](/source/Regression_(medicine)) with [neuropsychiatric](/source/Neuropsychiatric) symptoms such as [catatonia](/source/Catatonia), possibly caused by an autoimmune disease.[55] It primarily appears in teenagers and younger adults.[56]

### Senses

[Brushfield spots](/source/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.[29]

#### Ocular findings

[Brushfield spots](/source/Brushfield_spots) (small white or grayish/brown spots on the periphery of the [iris](/source/Iris_(anatomy))), upward slanting [palpebral fissures](/source/Palpebral_fissure) (the opening between the upper and lower lids) and [epicanthal folds](/source/Epicanthic_folds) (folds of skin between the upper eyelid and the nose) are clinical signs at birth suggesting the diagnosis of Down syndrome[57][58] especially in the [Western World](/source/Western_world).[58] None of these requires treatment.[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]

Visually significant congenital [cataracts](/source/Cataract) (clouding of the [lens](/source/Lens_(vertebrate_anatomy)) of the eye) occur more frequently with Down syndrome.[58] [Neonates](/source/Infant) with Down syndrome should be screened for cataract because early recognition and referral reduce the risk of vision loss from [amblyopia](/source/Amblyopia).[59] Dot-like opacities in the cortex of the [lens](/source/Lens_(anatomy)) (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.[58]

[Strabismus](/source/Strabismus), [nystagmus](/source/Nystagmus) and [nasolacrimal duct obstruction](/source/Nasolacrimal_duct_obstruction) occur more frequently in children with Down syndrome.[58] Screening for these diagnoses should begin within six months of birth.[58][59] Strabismus is more often acquired than [congenital](/source/Congenital).[58] Early diagnosis and treatment of strabismus reduces the risk of vision loss from amblyopia.[60] In Down syndrome, the presence of epicanthal folds may give the false impression of strabismus, referred to as [pseudostrabismus](/source/Pseudostrabismus). Nasolacrimal duct obstruction, which causes tearing ([epiphora](/source/Epiphora_(medicine))), is more frequently bilateral and multifactorial than in children without Down syndrome.[58]

[Refractive error](/source/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.[58] Early screening is recommended to identify and treat significant refractive error with glasses or contact lenses. Poor [accommodation](/source/Accommodation_reflex) (ability to focus on close objects) is associated with Down syndrome, which may mean bifocals are indicated.[58]

In [keratoconus](/source/Keratoconus), the [cornea](/source/Cornea) progressively thins and bulges into a cone shape,[61] causing visual blurring or distortion. Keratoconus first presents in the teen years and progresses into the thirties.[61][62] 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.[58] Eye rubbing is also a risk factor for developing keratoconus.[62] It is speculated that chronic eye irritation from [blepharitis](/source/Blepharitis) may increase eye rubbing in Down syndrome,[58] contributing to the increased prevalence of keratoconus.

An association between [glaucoma](/source/Glaucoma) and Down syndrome is often cited.[57] Glaucoma in children with Down syndrome is uncommon, with a prevalence of less than 1%.[57][58] It is currently unclear if the prevalence of glaucoma in those with Down syndrome differs from that in the absence of Down syndrome.[58]

Estimates of [prevalence](/source/Prevalence) of ocular findings in Down syndrome vary widely depending on the study.[58] Some prevalence estimates follow. Vision problems have been observed in 38–80% of cases.[57] [Brushfield spots](/source/Brushfield_spots) are present in 38–85% of individuals.[57] Between 20 and 50% have [strabismus](/source/Strabismus).[57] [Cataracts](/source/Cataract) occur in 15%,[63] and may be present at birth.[57] [Keratoconus](/source/Keratoconus) may occur in as many as 21–30%.[58]

#### Hearing loss

Hearing problems are found in 50–90% of children with Down syndrome.[64] This is often the result of [otitis media with effusion](/source/Otitis_media_with_effusion) which occurs in 50–70%[10] and chronic [ear infections](/source/Otitis_media) which occur in 40–60%.[65] Ear infections often begin in the first year of life and are partly due to poor [eustachian tube](/source/Eustachian_tube) function.[66][67] Excessive [ear wax](/source/Earwax) can also cause hearing loss due to obstruction of the outer [ear canal](/source/Ear_canal).[9] Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics.[1][67] It is important to rule out hearing loss as a factor in social and cognitive deterioration.[68] Age-related hearing loss of the [sensorineural type](/source/Sensorineural_hearing_loss) occurs at a much earlier age and affects 10–70% of people with Down syndrome.[9]

### Heart

The rate of [congenital heart disease](/source/Congenital_heart_disease) in newborns with Down syndrome is around 40%.[34] Of those with heart disease, about 80% have an [atrial septal defect](/source/Atrial_septal_defect) or [ventricular septal defect](/source/Ventricular_septal_defect) with the former being more common.[9] Congenital heart disease can also put individuals at a higher risk of [pulmonary hypertension](/source/Pulmonary_hypertension), where arteries in the lungs narrow and cause inadequate blood oxygenation.[69] Some of the genetic contributions to pulmonary hypertension in individuals with Down syndrome are abnormal lung development, [endothelial dysfunction](/source/Endothelial_dysfunction), and proinflammatory genes.[69] [Mitral valve](/source/Mitral_valve) problems become common as people age, even in those without heart problems at birth.[9] Other problems that may occur include [tetralogy of Fallot](/source/Tetralogy_of_Fallot) and [patent ductus arteriosus](/source/Patent_ductus_arteriosus).[66] People with Down syndrome have a lower risk of [hardening of the arteries](/source/Atherosclerosis).[9]

### Cancer

Although the overall risk of [cancer](/source/Cancer) in Down syndrome is not changed,[70] the risk of [testicular cancer](/source/Testicular_cancer) and certain blood cancers, including [acute lymphoblastic leukemia](/source/Acute_lymphoblastic_leukemia) (ALL) and [acute megakaryoblastic leukemia](/source/Acute_megakaryoblastic_leukemia) (AMKL) is increased while the risk of other non-blood cancers is decreased.[9] People with Down syndrome are believed to have an increased risk of developing cancers derived from [germ cells](/source/Germ_cell) whether these cancers are blood- or non-blood-related.[71] In 2008, the World Health Organization (WHO) introduced a distinct classification for myeloid proliferation in individuals with Down syndrome.[72]

#### Blood cancers

[Leukemia](/source/Leukemia) is 10 to 15 times more common in children with Down syndrome.[29] In particular, [acute lymphoblastic leukemia](/source/Acute_lymphoblastic_leukemia) (ALL) is 20 times more common and the megakaryoblastic form of [acute myeloid leukemia](/source/Acute_myeloid_leukemia) (AML), called [acute megakaryoblastic leukemia](/source/Acute_megakaryoblastic_leukemia) (AMLK), is 500 times more common.[73] AMKL is a leukemia of [megakaryoblasts](/source/Megakaryoblast), the precursors cells to [megakaryocytes](/source/Megakaryocyte) which form blood [platelets](/source/Platelet). ALL 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](/source/White_blood_cell_count) greater than 50,000 per [microliter](/source/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.[73][74] In short, the likelihood of developing AML and ALL is higher in children with Down syndrome compared to those without Down syndrome.[75]

[Myeloid leukemia](/source/Myeloid_leukemia) typically precedes Down syndrome and is accompanied by a condition known as [transient abnormal myelopoiesis](/source/Transient_myeloproliferative_disease) (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes.[76] In Down syndrome, AMKL is typically preceded by [transient myeloproliferative disease](/source/Transient_myeloproliferative_disease) (TMD), a disorder of [blood cell production](/source/Haematopoiesis) in which non-cancerous megakaryoblasts with a mutation in the *[GATA1](/source/GATA1)* gene rapidly divide during the later period of pregnancy.[73][77] GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM.[78] 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.[76] The condition affects 3–10% of babies with Down.[73] While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications.[79] In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.[73][79][78]

#### 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.[71] This low risk is thought to be due to an increase in the expression of [tumor suppressor genes](/source/Tumor_suppressor_gene) present on chromosome 21.[80][71] One exception is testicular [germ cell cancer](/source/Germ_cell_tumor) which occurs at a higher rate in Down syndrome.[71]

### Endocrine

Problems of the [thyroid gland](/source/Thyroid_gland) occur in 20–50% of individuals with Down syndrome.[9][29] [Low thyroid](/source/Hypothyroidism) is the most common form, occurring in almost half of all individuals.[9] Thyroid problems can be due to a poorly or nonfunctioning thyroid at birth (known as [congenital hypothyroidism](/source/Congenital_hypothyroidism)) which occurs in 1%[10] or can develop later due to an attack on the thyroid by the [immune system](/source/Immune_system) resulting in [Graves' disease](/source/Graves'_disease) or [autoimmune hypothyroidism](/source/Autoimmune_hypothyroidism).[81] [Type 1 diabetes mellitus](/source/Type_1_diabetes_mellitus) is also more common.[9]

### Gastrointestinal

[Constipation](/source/Constipation) occurs in nearly half of people with Down syndrome and may result in changes in behavior.[29] One potential cause is [Hirschsprung's disease](/source/Hirschsprung's_disease), occurring in 2–15%, which is due to a lack of [nerve cells](/source/Neuron) controlling the [colon](/source/Colon_(anatomy)).[82] Other congenital problems can include [duodenal atresia](/source/Duodenal_atresia), [imperforate anus](/source/Imperforate_anus) and [gastroesophageal reflux disease](/source/Gastroesophageal_reflux_disease).[66] [Celiac disease](/source/Celiac_disease) affects about 7–20%.[9][29]

### Teeth

People with Down syndrome tend to be more susceptible to [gingivitis](/source/Gingivitis) as well as early, severe [periodontal](/source/Periodontal_pathology) disease, [necrotising ulcerative gingivitis](/source/Acute_necrotizing_ulcerative_gingivitis), and early [tooth loss](/source/Tooth_loss), especially in the lower front teeth.[83][84] While [plaque](/source/Dental_plaque) and poor [oral hygiene](/source/Oral_hygiene) are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors.[84] Research suggests that the severity is likely a result of a weakened immune system.[84][85] The weakened immune system also contributes to increased incidence of [yeast infections](/source/Candidiasis) in the mouth (from *[Candida albicans](/source/Candida_albicans)*).[85]

People with Down syndrome also tend to have a more [alkaline](/source/Alkaline) [saliva](/source/Saliva) resulting in a greater resistance to [tooth decay](/source/Tooth_decay), despite decreased quantities of saliva,[86] less effective oral hygiene habits, and higher plaque indexes.[83][85][86][87]

Higher rates of tooth wear and [bruxism](/source/Bruxism) are also common.[85] Other common oral manifestations of Down syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, [mouth breathing](/source/Mouth_breathing), narrow [palate](/source/Palate) with crowded teeth, class III [malocclusion](/source/Malocclusion) with an underdeveloped maxilla and posterior [crossbite](/source/Crossbite), delayed exfoliation of [baby teeth](/source/Baby_teeth) and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth.[83][85][86][87] Less common manifestations include [cleft lip and palate](/source/Cleft_lip_and_palate) and [enamel hypocalcification](/source/Enamel_hypocalcification) (20% prevalence).[87]

[Taurodontism](/source/Taurodontism), an elongation of the pulp chamber, has a high prevalence in people with DS.[88][89]

### Fertility

Males with Down syndrome usually do not father children, while females have lower rates of [fertility](/source/Fertility) relative to those who are unaffected.[90] Fertility is estimated to be present in 30–50% of females.[91] [Menopause](/source/Menopause) usually occurs at an earlier age.[9] The poor fertility in males is thought to be due to problems with [sperm development](/source/Spermatogenesis); however, it may also be related to not being sexually active.[90] Without [assisted reproductive technologies](/source/Preimplantation_genetic_diagnosis), around half of the children of someone with Down syndrome will also have the syndrome.[90][92]

## Cause

Main article: [Genetics of Down syndrome](/source/Genetics_of_Down_syndrome)

Down syndrome is caused by having three copies of the [genes](/source/Gene) on [chromosome 21](/source/Chromosome_21), rather than the usual two.[3][93] The parents of the affected individual are typically genetically normal.[14] 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](/source/Karyotype).[91]

There are three types of causes for Down syndrome:[15]

1. *Trisomy 21*: 94% of the time Down syndrome is caused by an extra copy of chromosome 21 in all cells,

1. *Translocation*: 4% of cases extra chromosome 21 material is attached to another chromosome,

1. *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](/source/Trisomy) 21.[92][94] In 1–2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as [mosaic](/source/Mosaic_(genetics)) Down syndrome.[91][95] The other common mechanisms that can give rise to Down syndrome include: a [Robertsonian translocation](/source/Robertsonian_translocation), [isochromosome](/source/Isochromosome), or [ring chromosome](/source/Ring_chromosome). These contain additional material from chromosome 21 and occur in about 2.5% of cases.[29][91] An isochromosome results when the two [long arms](/source/Q_arm) of a chromosome separate together rather than the long and [short arm](/source/P-arm) separating together during [egg or sperm development](/source/Meiosis).[92]

### Trisomy 21

The trisomy 21 version of Down syndrome (also known by the [karyotype](/source/Karyotype) 47,XX,+21 for females and 47,XY,+21 for males)[96] is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development, known as [nondisjunction](/source/Nondisjunction).[92] 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.[3][92] 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.[97]

The root cause of the extra full or partial chromosome is still unknown.[98] Most of the time, the extra chromosome results from a random mistake in cell division during early development of the fetus.[99] 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](/source/Advanced_maternal_age) but about 10 per cent of cases are associated with advanced [paternal age](/source/Paternal_age_effect).[100]

[Karyotype](/source/Karyotype) for Down syndrome (trisomy 21) showing the three copies of [chromosome 21](/source/Chromosome_21)

### Translocation Down syndrome

The extra chromosome 21 material may also occur due to a [Robertsonian translocation](/source/Robertsonian_translocation) in 2–4% of cases.[91][101] In this translocation Down syndrome, the long arm of chromosome 21 is attached to another chromosome, often [chromosome 14](/source/Chromosome_14_(human)).[102] In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q).[102][103] This may be a new mutation or previously present in one of the parents.[104] The parent with such a translocation is usually normal physically and mentally;[102] however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists.[101] 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.[104] The probability of this type of Down syndrome is not related to the mother's age.[102] Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome.[102] In this case it is sometimes known as *familial* Down syndrome.[105]

### Mosaic Down syndrome

[Mosaic](/source/Mosaic_(genetics)) 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.[17] This type is the least common form of Down syndrome and accounts for only about 1% of all cases.[98] 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.[17]

## Mechanism

The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21.[93] This overexpression has been estimated at 50%, due to the third copy of the chromosome present.[91] Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3,[106] with this area including genes for the [amyloid precursor protein](/source/Amyloid_precursor_protein), [superoxide dismutase](/source/Superoxide_dismutase), and likely the [ETS2](/source/ETS2) proto [oncogene](/source/Oncogene).[107] Other research, however, has not confirmed these findings.[93] [MicroRNAs](/source/MicroRNA) are also proposed to be involved.[108]

The dementia that occurs in Down syndrome is due to an excess of [amyloid beta](/source/Amyloid_beta) [peptide](/source/Peptide) produced in the brain and is similar to [Alzheimer's disease](/source/Alzheimer's_disease), which also involves amyloid beta build-up.[109] Amyloid beta is processed from amyloid precursor protein, the gene for which is located on chromosome 21.[109] [Senile plaques](/source/Senile_plaques) and [neurofibrillary tangles](/source/Neurofibrillary_tangle) are present in nearly all by 35 years of age, though dementia may not be present.[14] It is hypothesized that those with Down syndrome lack a normal number of [lymphocytes](/source/Lymphocytes) and produce less [antibodies](/source/Antibody) which is said to present an increased risk of infection.[29]

### 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](/source/Epigenetic_clock), it is hypothesized that trisomy 21 increases the age of blood and brain tissue (on average by 6.6 years).[110]

## Diagnosis

### Screening before birth

Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age.[111][112] A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate.[29] None can be definitive; thus, if screening predicts a high possibility of Down syndrome, either [amniocentesis](/source/Amniocentesis) or [chorionic villus sampling](/source/Chorionic_villus_sampling) is required to confirm the diagnosis.[111]

#### Ultrasound

[Prenatal ultrasound](/source/Prenatal_ultrasound) can be used to screen for Down syndrome. Findings that indicate increased chances when seen at 14 to 24 weeks of [gestation](/source/Gestation) include a small or no nasal bone, [large ventricles](/source/Ventriculomegaly), [nuchal fold thickness](/source/Nuchal_fold_thickness), and an abnormal right [subclavian artery](/source/Subclavian_artery), among others.[113] The presence or absence of many markers is more accurate.[113] Increased fetal [nuchal translucency](/source/Nuchal_translucency) (NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.[114]

		- Ultrasound of fetus with Down syndrome showing a [large bladder](/source/Megacystis)

		- 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.[115][116] Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results.[115] In the second trimester, often two or three tests are used in combination with two or three of: [α-fetoprotein](/source/%CE%91-fetoprotein), unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases.[116]

Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester.[117][118] 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.[119] Accuracy has been reported at 98.6% in the first trimester of pregnancy.[29] Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.[119]

#### Combinations

First- and second-trimester screening[111] 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 From 10 wks[120] 96–100%[117] 0.3%[121] 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.[111] Common screening techniques in use are able to pick up 90–95% of cases, with a false-positive rate of 2–5%.[115] 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.[115]

#### Invasive genetic testing

Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of [miscarriage](/source/Miscarriage) by between 0.5–1%.[122] The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks.[122]

An example of an algorithm for determining the indication for prenatal genetic testing of Down syndrome[123]

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.[122]

### Abortion rates

About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated.[22] As a result, there is almost no one with Down syndrome in [Iceland](/source/Iceland) and [Denmark](/source/Denmark), where screening is commonplace.[124] In the United States, the termination rate after diagnosis is around 75%,[124] but varies from 61 to 93%, depending on the population surveyed.[21] Rates are lower among women who are younger and have decreased over time.[21] 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.[125]

### After birth

A diagnosis can often be suspected based on the child's physical appearance at birth.[10] An analysis of the child's chromosomes is needed to confirm the diagnosis, and to determine if a [translocation](/source/Chromosomal_translocation) is present, as this may help determine the chances of the child's parents having further children with Down syndrome.[10]

## Management

Efforts such as [early childhood intervention](/source/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.[126] Education and proper care can provide a positive [quality of life](/source/Quality_of_life).[7] Typical childhood [vaccinations](/source/Vaccination) are recommended.[29]

### Health screening

Recommended screening Testing Children[127] Adults[9] 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](/source/Screening_(medicine)) those with Down syndrome for particular diseases.[127] This is recommended to be done systematically.[29]

At birth, all children should get an [electrocardiogram](/source/Electrocardiogram) and [ultrasound of the heart](/source/Echocardiogram).[29] Surgical repair of heart problems may be required as early as three months of age.[29] [Heart valve](/source/Heart_valve) problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood.[29] Due to the elevated risk of testicular cancer, some recommend checking the person's testicles yearly.[9]

### Cognitive development

Some people with Down syndrome experience hearing loss. In this instance, [hearing aids](/source/Hearing_aids) or other amplification devices can be useful for language learning.[29] [Speech therapy](/source/Speech-Language_Pathology) may be useful and is recommended to be started around nine months of age.[29] As those with Down syndrome typically have good hand-eye coordination, learning [sign language](/source/Sign_language) is a helpful communication tool.[47] [Augmentative and alternative communication](/source/Augmentative_and_alternative_communication) methods, such as pointing, body language, objects, or pictures, are often used to help with communication.[128] Behavioral issues and mental illness are typically managed with counseling or medications.[10]

Education programs before reaching school age may be useful.[1] School-age children with Down syndrome may benefit from [inclusive education](/source/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.[129] In the United States, the [Individuals with Disabilities Education Act](/source/Individuals_with_Disabilities_Education_Act) of 1975 requires public schools generally to allow attendance by students with Down syndrome.[130]

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.[131] 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.[132]

### Physical therapy

Therapeutic exercise helps individuals with Down syndrome improve muscle strength, balance, coordination, and gait. Therapeutic exercise is widely used to improve motor function. Interventions typically include aerobic training, resistance (strength) training, balance exercises, and neuromuscular activities. These programs are often structured with specific parameters such as frequency, intensity, and duration to target functional outcomes. A 2023 systematic review and meta-analysis found that combined aerobic and resistance training significantly improves muscle strength in both upper and lower extremities, while aerobic exercise improves gait parameters and dynamic balance. Improvements in these areas may enhance functional mobility and the ability to perform activities of daily living. However, the overall certainty of evidence is considered low to moderate.[133] For children ages 0-3, there is some evidence that therapeutic exercises such as aerobic treadmill training may help gait and motor development.[134]

### Other

[Tympanostomy tubes](/source/Tympanostomy_tube) are often needed[29] and often more than one set during the person's childhood.[64] [Tonsillectomy](/source/Tonsillectomy) is also often done to help with sleep apnea and [throat infections](/source/Pharyngitis).[29] Surgery does not correct every instance of sleep apnea and a [continuous positive airway pressure](/source/Continuous_positive_airway_pressure) (CPAP) machine may be useful in those cases.[64]

Efforts to prevent [respiratory syncytial virus](/source/Respiratory_syncytial_virus) (RSV) infection with [human monoclonal antibodies](/source/Human_monoclonal_antibodies) should be considered, especially in those with heart problems.[1] In those who develop dementia there is no evidence for [memantine](/source/Memantine),[135] [donepezil](/source/Donepezil),[136] [rivastigmine](/source/Rivastigmine),[137] or [galantamine](/source/Galantamine).[138]

## Prognosis

The examples and perspective in this section deal primarily with US and Sweden and do not represent a worldwide view of the subject. You may improve this section, discuss the issue on the talk page, or create a new section, as appropriate. (January 2025) (Learn how and when to remove this message)

Deaths due to Down syndrome per million persons in 2012

  0

  1

  2

  3

  4

  5

  6

  7–8

  9–16

Between 5–15% of children with Down syndrome in Sweden attend regular school.[139] Some graduate from high school; however, most do not.[24] Of those with intellectual disability in the United States who attended high school about 40% graduated.[140] Many learn to read and write and some are able to do paid work.[24] In adulthood about 20% in the United States do paid work in some capacity.[25][141] In Sweden, however, less than 1% have regular jobs.[139] Many are able to live semi-independently,[14] but they often require help with financial, medical, and legal matters.[10] Those with mosaic Down syndrome usually have better outcomes.[91]

Individuals with Down syndrome have a higher risk of early death than the general population.[29] This is most often from heart problems or infections.[1][9] Following improved medical care, particularly for heart and [gastrointestinal problems](/source/Gastrointestinal_problem), the life expectancy has increased.[1] This increase has been from 12 years in 1912,[142] to 25 years in the 1980s,[1] to 50 to 60 years in the developed world in the 2000s.[9][10] Data collected between the 1985–2003 showed between 4–12% infants with Down syndrome die in the first year of life.[79] 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.[14] In those without heart problems, 85% studied survived to at least 10 years and 80% survived to at least 30 years of age.[14] It is estimated that 10% lived to 70 years of age in the early 2000s.[92] Much of this data is outdated and life expectancy has drastically improved with more equitable healthcare and continuous advancement of surgical practice.[143] The [National Down Syndrome Society](/source/National_Down_Syndrome_Society) provides information regarding raising a child with Down syndrome.[144]

## Epidemiology

The risk of having a Down syndrome pregnancy in relation to a [mother's age](/source/Advanced_maternal_age)[4]

Down syndrome is the most common chromosomal abnormality in humans.[9] Globally, as of 2010[\[update\]](https://en.wikipedia.org/w/index.php?title=Down_syndrome&action=edit), Down syndrome occurs in about 1 per 1,000 births[1] and results in about 17,000 deaths.[145] 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.[1] About 1.4 per 1,000 live births in the United States[146] and 1.1 per 1,000 live births in Norway are affected.[9] 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.[104] The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting.[10] It is the cause of 8% of all [congenital disorders](/source/Congenital_disorders).[1]

[Maternal age](/source/Maternal_age_effect) affects the chances of having a pregnancy with Down syndrome.[4] 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.[4] 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.[4] The [father's older age](/source/Paternal_age_effect) 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.[147]

## History

Levitas and Reid have suggested that this [early Netherlandish painting](/source/Early_Netherlandish_painting), *The Adoration of the Christ Child*, depicts a person with Down syndrome as one of the angels.[148]

[John Langdon Haydon Down](/source/John_Langdon_Down) — first described Down syndrome

The English physician [John Langdon Down](/source/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.[29][149][150] [Édouard Séguin](/source/%C3%89douard_S%C3%A9guin) described it as separate from [cretinism](/source/Cretinism) in 1844.[30][151] 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](/source/Mongoloid), John Langdon Down used the term "[Mongoloid](/source/Mongolian_idiocy)".[152] Down felt that the symptoms of Down syndrome in Europeans provided evidence that [all peoples were genetically related](/source/Monogenism):[153]

If these great racial divisions are fixed and definite, how comes it that disease is able to break down the barrier, and to simulate so closely the features of the members of another division. I cannot but think that the observations which I have recorded, are indications that the differences in the races are not specific but variable. These examples of the result of degeneracy among mankind, appear to me to furnish some arguments in favor of the unity of the human species.[154]

In the 1950s with discovery of the underlying cause as being related to chromosomes, concerns about the race-based nature of the name increased.[155]

In 1961, a group of nineteen scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term".[156] The [World Health Organization](/source/World_Health_Organization) (WHO) dropped the term in 1965 after a request by the delegation from the [Mongolian People's Republic](/source/Mongolian_People's_Republic).[157] While this terminology continued to be used until the late twentieth century,[158]: 21 it is now considered unacceptable and is no longer in common use.

In antiquity, many infants with disabilities were either killed or abandoned.[30] 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](/source/Poulnabrone_dolmen) in [Ireland](/source/Ireland).[159] Researchers believe that a number of historical pieces of art portray Down syndrome, including pottery from the [pre-Columbian](/source/Pre-Columbian) Tumaco-La Tolita culture in present-day [Colombia](/source/Colombia) and [Ecuador](/source/Ecuador),[160] and the 16th-century painting *The Adoration of the Christ Child*.[161][162]

In the 20th century, many people 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](/source/Eugenics_movement), 33 of the then 48 [US states](/source/US_state) and several countries began programs of forced sterilization of individuals with Down syndrome and comparable degrees of disability. [Action T4](/source/Action_T4) in [Nazi Germany](/source/Nazi_Germany) saw the systematic murder of people with Down syndrome made public policy.[163]

With the discovery of [karyotype](/source/Karyotype) techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape.[151] In 1959 [Jérôme Lejeune](/source/J%C3%A9r%C3%B4me_Lejeune) reported the discovery that Down syndrome resulted from an extra chromosome.[29] However, Lejeune's claim to the discovery has been disputed,[164] and in 2014 the Scientific Council of the French Federation of Human Genetics unanimously awarded its Grand Prize to his colleague [Marthe Gautier](/source/Marthe_Gautier) for her role in this discovery.[165] The discovery took place in the laboratory of [Raymond Turpin](/source/Raymond_Turpin) at the Hôpital Trousseau in Paris, France.[166] Jérôme Lejeune and Marthe Gautier were both his students.[167]

As a result of this discovery, the condition became known as trisomy 21, especially in European countries.[168] 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.[169]

## Society and culture

See also: [List of people with Down syndrome](/source/List_of_people_with_Down_syndrome)

### Name

Down syndrome is named after [John Langdon Down](/source/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.[170] While others had previously recognized components of the condition, John Langdon Down described the syndrome as a distinct, unique medical condition.[18]

In 1975, the United States [National Institutes of Health](/source/National_Institutes_of_Health) (NIH) convened a conference to standardize the naming and recommended replacing the possessive form, "Down's syndrome", with "Down syndrome".[171] However, both the possessive and nonpossessive forms remain in use by the general population,[12] and in the United Kingdom the [NHS](/source/National_Health_Service) uses the term *Down's syndrome* in its patient-oriented information.[172] The term "trisomy 21" is also commonly used.[156][173]

### Ethics

Obstetricians routinely offer antenatal screenings for various conditions, including Down syndrome.[174][175] When results from testing become available, it is considered an ethical requirement to share the results with the patient.[174][176]

Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being.[177] One criticism of this reasoning is that it often values those with disabilities less.[178] Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide.[179][180] The [disability rights movement](/source/Disability_rights) does not have a position on screening,[181] although some members consider testing and abortion discriminatory.[181] Some in the United States who are [anti-abortion](/source/Anti-abortion) support abortion if the fetus is disabled, while others do not.[182] 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.[182]

Within the US, some [Protestant](/source/Protestant) denominations see abortion as acceptable when a fetus has Down syndrome while [Orthodox Christianity](/source/Eastern_Orthodox_Church) and [Roman Catholicism](/source/Roman_Catholics) do not.[183] Women may face disapproval whether they choose abortion or not.[184] Some of those against screening refer to it as a form of [eugenics](/source/Eugenics).[183]

### Advocacy groups

Advocacy groups for individuals with Down syndrome began to be formed after the [Second World War](/source/World_War_II).[185] 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,[185] as well as groups providing support for families with children living with Down syndrome.[185] Before this individuals with Down syndrome were often placed in [mental hospitals or asylums](/source/History_of_psychiatric_institutions). Organizations included the [Royal Society for Handicapped Children and Adults](/source/Mencap) founded in the UK in 1946 by [Judy Fryd](/source/Judy_Fryd),[185][186] Kobato Kai founded in Japan in 1964,[185] the National Down Syndrome Congress founded in the United States in 1973 by [Kathryn McGee](/source/Kathryn_McGee) and others,[185][187] and the [National Down Syndrome Society](/source/National_Down_Syndrome_Society) founded in 1979 in the United States.[185] The first Roman Catholic order of nuns for women with Down Syndrome, [Little Sisters Disciples of the Lamb](/source/Little_Sisters_Disciples_of_the_Lamb), was founded in 1985 in France.[188]

The first [World Down Syndrome Day](/source/World_Down_Syndrome_Day) was held on 21 March 2006.[189] The day and month were chosen to correspond with 21 and trisomy, respectively.[190] It was recognized by the [United Nations General Assembly](/source/United_Nations_General_Assembly) in 2011.[189]

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](/source/Paralympic_Games).[191] 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.[192][193]

### Paralympic swimming

[International Paralympic Committee](/source/International_Paralympic_Committee) [Para-swimming classification](/source/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](/source/Para_swimming) [S14](/source/S14_(classification)) intellectual impairment category (provided they score low in IQ tests), they are often outmatched by the superior physicality of their opponents.[194][195]

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.[196][197]

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.[198]

Despite ongoing advocacy, the issue remains unresolved, and swimmers with Down syndrome continue to face challenges in accessing appropriate classification pathways.[199][200]

## Research

See also: [Down syndrome research](/source/Down_syndrome_research) and [Mouse models of Down syndrome](/source/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](/source/Gene_therapy) seems like a promising approach, tailored treatments may be required.[201] Gene therapy delivered via [stem cells](/source/Stem_cells) has been proposed as a tool for studying the syndrome[202] and as an approach to therapy.[203] Other methods being studied include the use of [antioxidants](/source/Antioxidant), [gamma secretase inhibition](/source/Gamma_secretase_inhibition), [adrenergic agonists](/source/Adrenergic_agonist), and [memantine](/source/Memantine).[204] Research is often carried out on an [animal model](/source/Animal_model), the [Ts65Dn mouse](/source/Mouse_models_of_Down_syndrome).[205] Some research seeks to develop appropriate screening tools to determine appropriate treatment strategies should they prove successful.[206]

## Other hominids

Down syndrome may also occur in [hominids](/source/Hominidae) other than humans. In [great apes](/source/Great_apes) chromosome 22 corresponds to the human chromosome 21[a] and thus trisomy 22 causes Down syndrome in apes. The condition was observed in a [common chimpanzee](/source/Common_chimpanzee) in 1969 and a [Bornean orangutan](/source/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.[208][209] Kanako was blind, relatively small, and targeted by aggressive group mates. Kanako died in the Kumamoto Sanctuary at [Kyoto University](/source/Kyoto_University) in 2020.[210]

Fossilized remains of a [Neanderthal](/source/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](/source/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.[211][212]

## In popular culture

 [Chris Burke](/source/Chris_Burke_(actor)), an actor with Down syndrome, born in 1965

### Individuals

- [Jamie Brewer](/source/Jamie_Brewer) is an American actress and model. She is best known for her roles in the [FX](/source/FX_(TV_channel)) horror anthology television series *[American Horror Story](/source/American_Horror_Story)*.[213] In its first season, *[Murder House](/source/American_Horror_Story%3A_Murder_House)*, she portrayed [Adelaide "Addie" Langdon](/source/Adelaide_Langdon); in the third season, *[Coven](/source/American_Horror_Story%3A_Coven)*, she portrayed [Nan](/source/Nan_(American_Horror_Story)), an enigmatic and [clairvoyant](/source/Clairvoyant) [witch](/source/Witch); in the fourth season *[Freak Show](/source/American_Horror_Story%3A_Freak_Show)*, she portrayed Chester Creb's vision of his doll, Marjorie; in the seventh season *[Cult](/source/American_Horror_Story%3A_Cult)*, she portrayed Hedda, a member of the 'SCUM' crew, led by feminist [Valerie Solanas](/source/Valerie_Solanas); and she also returned to her role as Nan in the eighth season, *[Apocalypse](/source/American_Horror_Story%3A_Apocalypse)*. In February 2015, Brewer became the first woman with Down syndrome to walk the red carpet at [New York Fashion Week](/source/New_York_Fashion_Week), for designer Carrie Hammer.[214]

- [Tommy Jessop](/source/Tommy_Jessop) is a British actor, author and activist. He starred in the [BAFTA](/source/BAFTA)-nominated dramas *[Coming Down the Mountain](/source/Coming_Down_the_Mountain)* and *[Line of Duty](/source/Line_of_Duty)*,[215][216] and was the first person with Down syndrome to play [Hamlet](/source/Hamlet) professionally as part of a touring production with [Blue Apple Theatre](/source/Blue_Apple_Theatre).[217] Jessop is a prominent campaigner in the UK and was a key figure in the creation of the [Down Syndrome Act 2022](/source/Down_Syndrome_Act_2022).[218] In 2023 [Headline Publishing Group](/source/Headline_Publishing_Group) published Jessop's autobiography *A Life Worth Living: Acting, Activism and Everything Else*.[219]

- [Sofía Jirau](/source/Sof%C3%ADa_Jirau) is a [Puerto Rican](/source/Puerto_Ricans) model with Down syndrome, working with designers and media outlets such as Vogue Mexico, People, and Hola!.[220][221][222] In February 2020, Jirau made her debut at [New York Fashion Week](/source/New_York_Fashion_Week).[223] Then in February 2022, she became the first-ever model with Down Syndrome to be hired by the American retail company [Victoria's Secret](/source/Victoria's_Secret).[224] She walked the [LA Fashion Week](/source/Los_Angeles_Fashion_Week) runway in 2022.[225] 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."[225]

- [Chris Nikic](/source/Chris_Nikic) is the first person with Down syndrome to finish an [Ironman Triathlon](/source/Ironman_Triathlon).[226] He was awarded the [Jimmy V Award for Perseverance](/source/Jimmy_V_Award) at the [2021 ESPY Awards](/source/2021_ESPY_Awards).[227] 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.[228]

- [Grace Strobel](/source/Grace_Strobel) is an American model and the first person with Down syndrome to represent an American skin-care brand.[229] She first joined Obagi in 2020, and continues to be an Ambassador for the brand as of 2022.[230][231] She walked the runway representing [Tommy Hilfiger](/source/Tommy_Hilfiger_(company)) for Runway of Dreams [New York Fashion Week](/source/New_York_Fashion_Week) 2020 and [Atlantic City Fashion Week](/source/Atlantic_City_Fashion_Week).[232] Strobel has been featured in *[Forbes](/source/Forbes)*, on [*The Today Show*](/source/Today_(American_TV_program)), *[Good Morning America](/source/Good_Morning_America)*, by [Rihanna](/source/Rihanna)'s [Fenty Beauty](/source/Fenty_Beauty), Lady Gaga's Kindness Channel, and many more.[232][233] She is also a public speaker and gives a presentation called #TheGraceEffect about what it is like to live with Down syndrome.[234][233]

### Television and film

- *[Life Goes On](/source/Life_Goes_On_(TV_series))* is an American drama television series that aired on [ABC](/source/American_Broadcasting_Company) from 12 September 1989, to 23 May 1993.[235] The show centers on the Thatcher family living in [suburban Chicago](/source/Chicago_metropolitan_area): Drew, his wife Libby, and their children Paige, Rebecca and Charles. Charles, called Corky on the show and portrayed by [Chris Burke](/source/Chris_Burke_(actor)), was the first major character on a television series with Down syndrome.[236] Burke's revolutionary role conveyed a realistic portrayal of people with Down syndrome and changed the way audiences viewed people with disabilities.[237]

- [*Champions*](/source/Champions_(2023_film)) (2023) is a film starring four main actors with Down syndrome: [Madison Tevlin](/source/Madison_Tevlin), Kevin Iannucci, Matthew Von Der Ahe and James Day Keith.[238] It is an American [sports](/source/Sports_film) [comedy](/source/Comedy_film) film directed by [Bobby Farrelly](/source/Bobby_Farrelly) in his [solo directorial debut](/source/List_of_directorial_debuts), from a screenplay written by Mark Rizzo. The film stars [Woody Harrelson](/source/Woody_Harrelson) as a temperamental [minor-league basketball](/source/NBA_G_League) coach who after an arrest must coach a team of players with intellectual disabilities as community service; [Kaitlin Olson](/source/Kaitlin_Olson), [Ernie Hudson](/source/Ernie_Hudson), and [Cheech Marin](/source/Cheech_Marin) also star.

- [*Born This Way*](/source/Born_This_Way_(TV_series)) is an [American](/source/Television_in_the_United_States) [reality television](/source/Reality_television) series produced by [Bunim/Murray Productions](/source/Bunim%2FMurray_Productions) featuring seven adults with Down syndrome with work hard to achieve goals and overcome obstacles.[239] The show received a Television Academy Honor in 2016.[240]

- *[The Peanut Butter Falcon](/source/The_Peanut_Butter_Falcon)* is a 2019 American [comedy-drama](/source/Comedy-drama) film written and directed by Tyler Nilson and Michael Schwartz, in their directorial film debut, and starring [Zack Gottsagen](/source/Zack_Gottsagen), [Shia LaBeouf](/source/Shia_LaBeouf), [Dakota Johnson](/source/Dakota_Johnson) and [John Hawkes](/source/John_Hawkes_(actor)).[241] The plot follows a young man with Down syndrome who escapes from an [assisted living facility](/source/Assisted_living), 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](/source/Social_work) attempts to track them.[242]

### Music

- The [Devo](/source/Devo) song "[Mongoloid](/source/Mongoloid_(song))" is about someone with Down syndrome.

- The [Amateur Transplants](/source/Amateur_Transplants) song "[Your Baby](/source/Fitness_to_Practice)" is about a fetus with Down syndrome.

### Toys

- In 2023, [Mattel](/source/Mattel) released a [Barbie](/source/Barbie) doll with characteristics of a person having Down syndrome as a way to promote diversity.[243]

## See also

- [List of syndromes](/source/List_of_syndromes)

- [Characteristics of syndromic ASD conditions](/source/Characteristics_of_syndromic_ASD_conditions)

## Notes

1. **[^](#cite_ref-208)** 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](/source/Chromosome_2) in humans.[207]

## References

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1. ^ [***a***](#cite_ref-Adv2011_185-0) [***b***](#cite_ref-Adv2011_185-1) [***c***](#cite_ref-Adv2011_185-2) [***d***](#cite_ref-Adv2011_185-3) [***e***](#cite_ref-Adv2011_185-4) [***f***](#cite_ref-Adv2011_185-5) [***g***](#cite_ref-Adv2011_185-6) Wright D (2011). ["Into the Mainstream"](https://books.google.com/books?id=lm0BrR0POj8C&pg=PA147). *Downs: The history of a disability*. Oxford University Press. p. 147. [ISBN](/source/ISBN_(identifier)) [978-0-19-161978-6](https://en.wikipedia.org/wiki/Special:BookSources/978-0-19-161978-6). [Archived](https://web.archive.org/web/20170123083050/https://books.google.com/books?id=lm0BrR0POj8C&pg=PA147) from the original on 23 January 2017.

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1. **[^](#cite_ref-vatican_188-0)** Vet C (24 July 2019). ["Religious Sisters with Down syndrome: the joy of shared contemplative life"](https://www.vaticannews.va/en/world/news/2019-07/stories-religious-sisters-with-down-syndrome.html). Vatican News. Retrieved 31 July 2019.

1. ^ [***a***](#cite_ref-WDSD2014_189-0) [***b***](#cite_ref-WDSD2014_189-1) ["World Down Syndrome Day"](http://www.ds-int.org/world-down-syndrome-day). *Down Syndrome International*. [Archived](https://web.archive.org/web/20140314001941/http://www.ds-int.org/world-down-syndrome-day) from the original on 14 March 2014. Retrieved 2 February 2014.

1. **[^](#cite_ref-190)** Pratt G, Rosner V (2012). [*The global and the intimate feminism in our time*](https://books.google.com/books?id=bWGPe649QjIC&pg=PA113). New York: Columbia University Press. p. 113. [ISBN](/source/ISBN_(identifier)) [978-0-231-52084-3](https://en.wikipedia.org/wiki/Special:BookSources/978-0-231-52084-3). [Archived](https://web.archive.org/web/20170123082556/https://books.google.com/books?id=bWGPe649QjIC&pg=PA113) from the original on 23 January 2017.

1. **[^](#cite_ref-191)** Resident P (25 March 2022). ["Special21 celebrates World Down Syndrome Day in Albufeira"](https://www.portugalresident.com/special21-celebrates-world-down-syndrome-day-in-albufeira/). *Portugal Resident*. Retrieved 13 March 2024.

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## Further reading

- Fox N (26 November 2021). ["'World-leading' Down's syndrome bill clears first hurdle in Parliament"](https://www.bbc.com/news/uk-politics-59432487). [BBC News](/source/BBC_News). [Archived](https://web.archive.org/web/20211127155428/https://www.bbc.com/news/uk-politics-59432487) from the original on 27 November 2021. Retrieved 27 November 2021.

- Thompson SB (1999). "Examining dementia in Down's syndrome (DS): decline in social abilities in DS compared with other learning disabilities". *Clinical Gerontologist*. **20** (3). Taylor & Francis (Routledge): 23–44. [doi](/source/Doi_(identifier)):[10.1300/j018v20n03_04](https://doi.org/10.1300%2Fj018v20n03_04). [ISSN](/source/ISSN_(identifier)) [1545-2301](https://search.worldcat.org/issn/1545-2301). [OCLC](/source/OCLC_(identifier)) [1106716083](https://search.worldcat.org/oclc/1106716083).

- Thompson SB (2000a). "The Central Executive System in people with Down's syndrome and dementia". *Clinical Gerontologist*. **21** (3). Taylor & Francis (Routledge): 3–32. [doi](/source/Doi_(identifier)):[10.1300/j018v21n03_02](https://doi.org/10.1300%2Fj018v21n03_02). [ISSN](/source/ISSN_(identifier)) [1545-2301](https://search.worldcat.org/issn/1545-2301). [OCLC](/source/OCLC_(identifier)) [1106716083](https://search.worldcat.org/oclc/1106716083). [S2CID](/source/S2CID_(identifier)) [218575706](https://api.semanticscholar.org/CorpusID:218575706).

- Thompson SB (2000b). "Investigation into Down's syndrome and dementia". *Journal of the Association of Practitioners in Learning Disability*. **17** (3): 10–14.

## External links

**Down syndrome**  at Wikipedia's [sister projects](https://en.wikipedia.org/wiki/Wikipedia:Wikimedia_sister_projects)

- [Media](https://commons.wikimedia.org/wiki/Category:Down_syndrome) from Commons
- [Quotations](https://en.wikiquote.org/wiki/Down_syndrome) from Wikiquote
- [Data](https://www.wikidata.org/wiki/Q47715) from Wikidata

- [Down's syndrome](https://www.nhs.uk/conditions/downs-syndrome/) by the UK [National Health Service](/source/National_Health_Service)

Classification D ICD-11: LD40.0 ICD-10: Q90 ICD-9-CM: 758.0 OMIM: 190685 MeSH: D004314 DiseasesDB: 3898 External resources MedlinePlus: 000997 eMedicine: ped/615 Patient UK: Down syndrome

v t e Autism Main Causes Diagnosis Epidemiology Epigenetics Heritability History Memory Pathophysiology Sex and gender Societal and cultural aspects Therapies Motor coordination Diagnoses Pervasive developmental disorder Autistic disorder Asperger syndrome Pervasive developmental disorder not otherwise specified Childhood disintegrative disorder High-functioning autism Associated conditions and phenomena Alexithymia Anxiety LGBTQ identities Catatonia Masking Echolalia Echopraxia Emotional dysregulation Hyperlexia Infodumping Late talker Monotropism Nonspeaking Pathological demand avoidance Pronoun reversal Reading differences Savant syndrome Special interests Stimming Sensory overload Suicide among people with autism Comorbid conditions Attention deficit hyperactivity disorder Avoidant/restrictive food intake disorder Avoidant personality disorder Anxiety disorder obsessive–compulsive disorder Bipolar disorder Developmental coordination disorder Developmental verbal dyspraxia Epilepsy Gender dysphoria Global developmental delay Intellectual disability Major depressive disorder Schizoid personality disorder Sensory processing disorder Sleep disorder Suicide Tinnitus Associated syndromes 16p11.2 deletion syndrome 16p11.2 duplication syndrome 17q12 microdeletion syndrome 22q13 deletion syndrome Angelman syndrome Beck–Fahrner syndrome CACNA1C-related disorders CHARGE syndrome Cohen syndrome Cornelia de Lange syndrome DiGeorge syndrome Down syndrome Dup15q Goldenhar syndrome Fetal valproate spectrum disorder Fragile X syndrome Jacobsen syndrome Malan syndrome MECP2 duplication syndrome Neurofibromatosis type I Noonan syndrome Multiple hamartoma syndrome O'Donnell-Luria–Rodan syndrome Pitt–Hopkins syndrome Rett syndrome Skraban–Deardorff syndrome Smith–Lemli–Opitz syndrome Sotos syndrome SYNGAP1-related intellectual disability Tatton-Brown–Rahman syndrome Timothy syndrome TRPM3-related neurodevelopmental disorder Tuberous sclerosis Williams syndrome Related issues Ableism Autistic rights movement Critical autism studies Discrimination Double empathy problem Employment Military service and conscription Multiple complex developmental disorder Neurodiversity Neuroqueer theory Peripheral neuropathy Reduced affect display Sanism Self-harm Suicidal ideation TEACCH program Twice exceptional Violence and autism Controversies Facilitated communication Lancet MMR autism fraud MMR vaccine Rapid prompting method Thiomersal Chelation Combating Autism Act Autistic supremacism Diagnostic scales Autism Diagnostic Interview Autism Diagnostic Observation Schedule Childhood Autism Rating Scale Gilliam Asperger's disorder scale Screening scales Autism-spectrum quotient Childhood Autism Spectrum Test Ritvo Autism and Asperger Diagnostic Scale Lists Autism-related topics Fictional characters Schools Accommodations Autism-friendly Curb cut effect Inclusive design Neurodiversity and labor rights Neuroinclusive design Sensory friendly Supported employment Universal design Category

v t e Chromosome abnormalities Autosomal Duplications, including trisomies 1q21.1 duplication syndrome 2q31.1 microduplication Trisomy 8 Trisomy 9 Tetrasomy 9p Distal trisomy 10q Patau syndrome 13 Trisomy 16 16p11.2 duplication syndrome Trisomy 18 Down syndrome 21 22q11.2 duplication syndrome Trisomy 22 Cat-eye syndrome 22 Deletions (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) 1 Wolf–Hirschhorn syndrome 4 Cri du chat syndrome/Chromosome 5q deletion syndrome 5 Williams syndrome 7 Jacobsen syndrome 11 Miller–Dieker syndrome/Smith–Magenis syndrome/17q12 microdeletion syndrome 17 DiGeorge syndrome 22 22q11.2 distal deletion syndrome 22 22q13 deletion syndrome 22 genomic imprinting Angelman syndrome/Prader–Willi syndrome (15) Distal 18q-/Proximal 18q- X/Y linked Monosomies Turner syndrome (45,X) Trisomies/tetrasomies, other karyotypes/mosaics Klinefelter syndrome (47,XXY) XXYY syndrome (48,XXYY) XXYYY syndrome (49,XXYYY) XXXY syndrome (48,XXXY) XXXYY syndrome (49,XXXYY) XXXXY syndrome (49,XXXXY) Trisomy X (47,XXX) Tetrasomy X (48,XXXX) Pentasomy X (49,XXXXX) XYY syndrome (47,XYY) XYYY syndrome (48,XYYY) XYYYY syndrome (49,XYYYY) 45,X/46,XY 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid Burkitt lymphoma t(8 MYC;14 IGH) Follicular lymphoma t(14 IGH;18 BCL2) Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) Acute lymphoblastic leukemia Myeloid Philadelphia chromosome t(9 ABL; 22 BCR) Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) Acute promyelocytic leukemia t(15 PML,17 RARA) Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other Ewing sarcoma t(11 FLI1; 22 EWS) Synovial sarcoma t(x SYT;18 SSX) Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) Myxoid liposarcoma t(12 DDIT3; 16 FUS) Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other Fragile X syndrome Uniparental disomy XX male syndrome/46,XX testicular disorders of sex development Marker chromosome Nullisomic Ring chromosome 6; 9; 14; 15; 18; 20; 21, 22

v t e Disability Main topics Disability Disability studies Medical model Social model Approaches IEP Inclusion Learning disability Mainstreaming Physical therapy driver rehabilitation Special needs school education Rights, law, support Rights Ableism/disablism Disability rights Pejorative terms Right to sit United States Law Accessibility Act NL NS ABCA ACA AMA AODA ADA Convention on the Rights of Persons with Disabilities Declaration on the Rights of Disabled Persons International Classification of Functioning, Disability and Health Services Services for mental disorders Services for disabled people Support DLA ODSP Rail SSDI SSI Students CNIB Activist groups CCD DPI MINDS Reach Canada Structural and assistive Accessible toilet Activities of daily living Assistance dog Assistive technology Curb cut Curb cut effect Inclusive design Independent living Mobility aid Orthotics and braces Personal Care Assistant Physical accessibility Prosthetics Redundant elevators Universal design Web accessibility Social issues Augmentative and alternative communication Conscription of people with disabilities Emotional or behavioral disability Invisible disability Disability and disasters Disability and LGBT identities Disability and religion Disability and poverty Disproportionality in special education Sexuality and disability Youth and disability Disability studies Models of disability Inspiration porn Bodymind Crip as verb Neuroqueer theory Deaf studies Eugenics Anthropology Geography Education Journals Arts, media, culture, sport Disability culture Disability art Disability in the arts Disability in children's literature Disability in horror films Disability in the media Parasports Deaflympics Paralympics Special Olympics Category Lists

Authority control databases International GND National United States France BnF data Japan Czech Republic Israel Other Encyclopedia of Modern Ukraine Yale LUX

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Adapted from the Wikipedia article [Down syndrome](https://en.wikipedia.org/wiki/Down_syndrome) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Down_syndrome?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.