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Wikipedia

Down syndrome

April 12, 2024

Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21.[3] It is usually associated with developmental delays, mild to moderate intellectual disability, and characteristic physical features.[1][12] There are three types of Down syndrome, all with the same features: Trisomy 21, the most common type; Mosaic Down syndrome, and Translocation Down syndrome.[13][14]

Down syndrome
Other namesDown's syndrome, Down's, trisomy 21
An eight-year-old boy displaying characteristic facial features of Down syndrome
SpecialtyMedical genetics, pediatrics
SymptomsDelayed development, characteristic physical features, mild to moderate intellectual disability[1]
Usual onsetMostly at conception, rarely after fertilization[2]
DurationLifelong
CausesThird copy of chromosome 21[3]
Risk factorsOlder age of mother, prior affected child[4][5]
Diagnostic methodPrenatal screening, genetic testing[6]
TreatmentPhysical therapy, Occupational therapy, Speech therapy, Educational support, Supported work environment[7][8]
PrognosisLife expectancy 50 to 60 years (developed world)[9][10]
Frequency5.4 million (0.1%)[1][11]
Named afterJohn Langdon Down

The parents of the affected individual are usually genetically normal.[15] The probability increases from less than 0.1% in 20-year-old mothers to 3% in those of age 45.[4] The extra chromosome is provided at conception as the egg and sperm combine.[16] A very small percentage of 1-2% gets the additional chromosome in the embryo stage and it only impacts some of the cells in the body; this is known as Mosaic Down syndrome.[17][18] Usually, babies get 23 chromosomes from each parent for a total of 46, whereas in Down syndrome, a third 21st chromosome is attached.[18] It is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability.[2] Down syndrome can be identified during pregnancy by prenatal screening, followed by diagnostic testing, or after birth by direct observation and genetic testing.[6] 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).[19][20][21]

There is no cure for Down syndrome.[22] Education and proper care have been shown to provide good quality of life.[7] Some children with Down syndrome are educated in typical school classes, while others require more specialized education.[8] Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education.[23] In adulthood, about 20% in the United States do paid work in some capacity,[24] with many requiring a sheltered work environment.[8] Support in financial and legal matters is often needed.[10] Life expectancy is around 50 to 60 years in the developed world, with proper health care.[9][10] Regular screening for health issues common in Down syndrome is recommended throughout the person's life.[9]

Down syndrome is the most common chromosomal abnormality.[25] It occurs in about 1 in 1,000 babies born each year.[1] In the US this figure is given as one in 700 births.[13] In 2015, Down syndrome was present in 5.4 million individuals globally and resulted in 27,000 deaths, down from 43,000 deaths in 1990.[11][26][27] It is named after British physician John Langdon Down, who fully described the syndrome in 1866.[28] Some aspects of the condition were described earlier by French psychiatrist Jean-Étienne Dominique Esquirol in 1838 and French physician Édouard Séguin in 1844.[29] The genetic cause of Down syndrome was discovered in 1959.[28]

Signs and symptoms

 
A boy with Down syndrome using a cordless drill to assemble a book case

Those with Down syndrome nearly always have physical and intellectual disabilities.[30] As adults, their mental abilities are typically similar to those of an 8- or 9-year-old.[9] At the same time, their emotional and social awareness is very high.[31] They can have poor immune function[15] and generally reach developmental milestones at a later age.[10] They have an increased risk of a number of health concerns, such as congenital heart defect, epilepsy, leukemia, and thyroid diseases.[28]

Characteristics Percentage Characteristics Percentage
Mental impairment 99%[32] Abnormal teeth 60%[33]
Stunted growth 90%[34] Slanted eyes 60%[15]
Umbilical hernia 90%[35] Shortened hands 60%[33]
Increased skin on back of neck 80%[28] Short neck 60%[33]
Low muscle tone 80%[36] Obstructive sleep apnea 60%[28]
Narrow roof of mouth 76%[33] Bent fifth finger tip 57%[15]
Flat head 75%[15] Brushfield spots in the iris 56%[15]
Flexible ligaments 75%[15] Single transverse palmar crease 53%[15]
Proportionally large tongue[37] 75%[36] Protruding tongue 47%[33]
Abnormal outer ears 70%[28] Congenital heart disease 40%[33]
Flattened nose 68%[15] Strabismus ≈35%[1]
Separation of first and second toes 68%[33] Undescended testicles 20%[38]

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, epicanthic folds, low muscle tone, a flat nasal bridge, a single crease of the palm, and a protruding tongue. A protruding tongue is caused by low tone and weak facial muscles, and often corrected with myofunctional exercises.[39] Some characteristic airway features can lead to obstructive sleep apnea in around half of those with Down syndrome.[28] Other common features include: excessive joint flexibility, extra space between big toe and second toe, single palm lines and short fingers.[33][36]

Instability of the atlantoaxial joint occurs in about 1-2%.[40] 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.[41] 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.[41]

Growth in height is slower, resulting in adults who tend to have short stature—the average height for men is 154 cm (5 ft 1 in), and for women is 142 cm (4 ft 8 in).[42] Individuals with Down syndrome are at increased risk for obesity as they age due to hypothyroidism, other medical issues and lifestyle.[28][43] Growth charts have been developed specifically for children with Down syndrome.[28]

Neurological

This syndrome causes about a third of cases of intellectual disability.[15] 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.[44] Walking is acquired in 50% of children after 24 months.[45]

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.[1][46] Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that.[47] As they age, the gap tends to widen between people with Down syndrome and their same-age peers.[46][48]

Commonly, individuals with Down syndrome have better language understanding than ability to speak.[28][46] Babbling typically emerges around 15 months on average.[49] 10-45% of those with Down syndrome have either a stutter or rapid and irregular speech, making it difficult to understand them.[50] After reaching 30 years of age, some may lose their ability to speak.[9]

They typically do fairly well with social skills.[28] Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability.[46] In children with Down syndrome, mental illness occurs in nearly 30% with autism occurring in 5–10%.[10] People with Down syndrome experience a wide range of emotions.[51] While people with Down syndrome are generally happy,[52] symptoms of depression and anxiety may develop in early adulthood.[9]

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.[9] This includes an increased risk of a specific type of seizure called infantile spasms.[28] Many (15%) who live 40 years or longer develop Alzheimer's disease.[53] In those who reach 60 years of age, 50–70% have the disease.[9]

Senses

 
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.[28] Vision problems occur in 38–80% of cases.[1] Between 20 and 50% have strabismus, in which the two eyes do not move together.[1] Cataracts (cloudiness of the lens of the eye) occur in 15%,[10] and may be present at birth.[1] Keratoconus (a thin, cone-shaped cornea)[9] and glaucoma (increased eye pressure) are also more common,[1] as are refractive errors requiring glasses or contacts.[9] Brushfield spots (small white or grayish/brown spots on the outer part of the iris) are present in 38–85% of individuals.[1]

Hearing problems are found in 50–90% of children with Down syndrome.[54] This is often the result of otitis media with effusion which occurs in 50–70%[10] and chronic ear infections which occur in 40–60%.[55] Ear infections often begin in the first year of life and are partly due to poor eustachian tube function.[56][57] Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal.[9] Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics.[1][57] It is important to rule out hearing loss as a factor in social and cognitive deterioration.[58] Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome.[9]

Heart

The rate of congenital heart disease in newborns with Down syndrome is around 40%.[33] Of those with heart disease, about 80% have an atrial septal defect or ventricular septal defect with the former being more common.[9] 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.[59] Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development, endothelial dysfunction, and proinflammatory genes.[59] 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 and patent ductus arteriosus.[56] People with Down syndrome have a lower risk of hardening of the arteries.[9]

Cancer

Although the overall risk of cancer in Down syndrome is not changed,[60] 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.[9] 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.[61] In 2008, the World Health Organization (WHO) introduced a distinct classification for myeloid proliferation in individuals with Down syndrome.[62]

Blood cancers

Leukemia is 10 to 15 times more common in children with Down syndrome.[28] 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.[63] Acute megakaryoblastic leukemia (AMKL) is a leukemia of megakaryoblasts, the precursors cells to megakaryocytes which form blood platelets.[63] 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.[63][64] 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.[65]

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.[66] 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.[63][67] GATA1 mutations combined with Trisomy 21 contribute to a predisposition to Transient Abnormal Myelopoiesis (TAM).[68] In Trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to the development of Transient Abnormal Myelopoiesis (TAM) on the preleukemic pathway.[66] The condition affects 3–10% of babies with Down.[63] While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications.[69] In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.[63][69][68]

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.[61] This low risk is thought to be due to an increase in the expression of tumor suppressor genes present on chromosome 21.[70][61] One exception is testicular germ cell cancer which occurs at a higher rate in Down syndrome.[61]

Endocrine

Problems of the thyroid gland occur in 20–50% of individuals with Down syndrome.[9][28] Low thyroid 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) which occurs in 1%[10] or can develop later due to an attack on the thyroid by the immune system resulting in Graves' disease or autoimmune hypothyroidism.[71] Type 1 diabetes mellitus is also more common.[9]

Gastrointestinal

Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior.[28] One potential cause is Hirschsprung's disease, occurring in 2–15%, which is due to a lack of nerve cells controlling the colon.[72] Other congenital problems can include duodenal atresia, imperforate anus and gastroesophageal reflux disease.[56] Celiac disease affects about 7–20%[9][28]

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.[73][74] While plaque and poor oral hygiene are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors.[74] Research suggests that the severity is likely a result of a weakened immune system.[74][75] The weakened immune system also contributes to increased incidence of yeast infections in the mouth (from Candida albicans).[75]

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,[76] less effective oral hygiene habits, and higher plaque indexes.[73][75][76][77]

Higher rates of tooth wear and bruxism are also common.[75] 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.[73][75][76][77] Less common manifestations include cleft lip and palate and enamel hypocalcification (20% prevalence).[77]

Taurodontism, an elongation of the pulp chamber, has a high prevalence in people with DS.[78][79]

Fertility

Males with Down syndrome usually do not father children, while females have lower rates of fertility relative to those who are unaffected.[80] Fertility is estimated to be present in 30–50% of females.[81] Menopause usually occurs at an earlier age.[9] 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.[80] As of 2006, three instances of males with Down syndrome fathering children and 26 cases of females having children have been reported.[80] Without assisted reproductive technologies, around half of the children of someone with Down syndrome will also have the syndrome.[80][82]

Cause

Main article: Genetics of Down syndrome

The cause of the extra full or partial chromosome is still unknown.[83] Most of the time, Down syndrome is caused by a random mistake in cell division during early development of the fetus, but not inherited,[84] and there is no scientific research which shows that environmental factors or the parents' activities contribute to Down syndrome. The only factor that has been linked to the increased chance of having a baby with Down syndrome is advanced parental age. This is mostly associated with advanced maternal age but about 10 per cent of cases are associated with advanced paternal age.[85]

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

Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two.[3][86] The parents of the affected individual are typically genetically normal.[15] 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.[81]

The extra chromosome content can arise through several different ways. The most common cause (about 92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21.[82][87] 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.[81][88] 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.[28][81] 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.[82]

Trisomy 21

Down syndrome (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males)[89] is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development, known as nondisjunction.[82] 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][82] 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.[90]

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.[13] This type is the least common form of Down syndrome and accounts for only about 1% of all cases.[83] 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.[13]

Translocation Down syndrome

The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% of cases.[81][91] In this translocation Down syndrome, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14.[92] In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q).[92][93] This may be a new mutation or previously present in one of the parents.[94] The parent with such a translocation is usually normal physically and mentally;[92] however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists.[91] 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.[94] The probability of this type of Down syndrome is not related to the mother's age.[92] Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome.[92] In this case it is sometimes known as familial Down syndrome.[95]

Mechanism

The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21.[86] This overexpression has been estimated at 50%, due to the third copy of the chromosome present.[81] Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3,[96] with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene.[97] Other research, however, has not confirmed these findings.[86] MicroRNAs are also proposed to be involved.[98]

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.[99] Amyloid beta is processed from amyloid precursor protein, the gene for which is located on chromosome 21.[99] Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age, though dementia may not be present.[15] 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.[28]

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).[100]

Diagnosis

Screening before birth

Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age.[101][102] A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate.[28] None can be definitive, thus if screening is positive, either amniocentesis or chorionic villus sampling is required to confirm the diagnosis.[101]

When screening tests predict a high possibility of Down syndrome, a more invasive diagnostic test (amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis.[101]

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.[103] The presence or absence of many markers is more accurate.[103] Increased fetal nuchal translucency (NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.[104]

  •  
    Ultrasound of fetus with Down syndrome showing a large bladder
  •  
    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.[105][106] Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results.[105] 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.[106]

Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester.[107][108] 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.[109] Accuracy has been reported at 98.6% in the first trimester of pregnancy.[28] Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.[109]

Combinations

First- and second-trimester screening[101]
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[110] 96–100%[107] 0.3%[111] 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.[101] The different screening techniques in use are able to pick up 90–95% of cases, with a false-positive rate of 2–5%.[105] If Down syndrome occurs in one in 500 pregnancies with a 90% detection rate and the test used has a 5% false-positive rate, this means, of 20 women who test positive on screening, only one will not have a fetus with Down syndrome confirmed.[105] If the screening test has a 2% false-positive rate, this means, of 50 women who test positive on screening, one will not have a fetus with Down syndrome.[105]

Invasive genetic testing

Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of miscarriage by between 0.5-1%.[112] The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks.[112]

 
An example of an algorithm for determining the indication for prenatal genetic testing of Down syndrome[113]

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.[112]

Abortion rates

About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated.[21] As a result, there is almost no one with Down syndrome in Iceland and Denmark, where screening is commonplace.[114] In the United States, the termination rate after diagnosis is around 75%,[114] but varies from 61 to 93%, depending on the population surveyed.[20] Rates are lower among women who are younger and have decreased over time.[20] 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.[115]

After birth

The diagnosis can often be suspected based on the child's physical appearance at birth.[10] Informing the parents of a diagnosis needs to be made as soon as possible, with care and sensitivity. Even an uncertain diagnosis needs to be informed of in the same way.[116] This allows for a longer time for processing the information.[116]

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.[10]

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.[117] Education and proper care can provide a positive quality of life.[7] Typical childhood vaccinations are recommended.[28]

Health screening

Recommended screening
Testing Children[118] 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 those with Down syndrome for particular diseases.[118] This is recommended to be done systematically.[28]

At birth, all children should get an electrocardiogram and ultrasound of the heart.[28] Surgical repair of heart problems may be required as early as three months of age.[28] Heart valve problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood.[28] 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 or other amplification devices can be useful for language learning.[28] Speech therapy may be useful and is recommended to be started around nine months of age.[28] As those with Down syndrome typically have good hand-eye coordination, learning sign language is a helpful communication tool.[46] Augmentative and alternative communication methods, such as pointing, body language, objects, or pictures, are often used to help with communication.[119] 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 (whereby students of differing abilities are placed in classes with their peers of the same age), provided some adjustments are made to the curriculum.[120] In the United States, the Individuals with Disabilities Education Act of 1975 requires public schools generally to allow attendance by students with Down syndrome.[121]

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.[122] 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.[123]

Other

Tympanostomy tubes are often needed[28] and often more than one set during the person's childhood.[54] Tonsillectomy is also often done to help with sleep apnea and throat infections.[28] Surgery does not correct every instance of sleep apnea and a continuous positive airway pressure (CPAP) machine may be useful in those cases.[54]

Efforts to prevent respiratory syncytial virus (RSV) infection with human monoclonal antibodies should be considered, especially in those with heart problems.[1] In those who develop dementia there is no evidence for memantine,[124] donepezil,[125] rivastigmine,[126] or galantamine.[127]

Prognosis

 
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.[128] Some graduate from high school; however, most do not.[23] Of those with intellectual disability in the United States who attended high school about 40% graduated.[129] Many learn to read and write and some are able to do paid work.[23] In adulthood about 20% in the United States do paid work in some capacity.[24][130] In Sweden, however, less than 1% have regular jobs.[128] Many are able to live semi-independently,[15] but they often require help with financial, medical, and legal matters.[10] Those with mosaic Down syndrome usually have better outcomes.[81]

Individuals with Down syndrome have a higher risk of early death than the general population.[28] This is most often from heart problems or infections.[1][9] Following improved medical care, particularly for heart and gastrointestinal problems, the life expectancy has increased.[1] This increase has been from 12 years in 1912,[131] 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.[69] 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.[15] In those without heart problems, 85% studied survived to at least 10 years and 80% survived to at least 30 years of age.[15] It is estimated that 10% lived to 70 years of age in the early 2000s.[82] Much of this data is outdated and life expectancy has drastically improved with more equitable healthcare and continuous advancement of surgical practice.[132] The National Down Syndrome Society provides information regarding raising a child with Down syndrome.[133]

Epidemiology

 
The risk of having a Down syndrome pregnancy in relation to a mother's age[4]

Down syndrome is the most common chromosomal abnormality in humans.[9] Globally, as of 2010, Down syndrome occurs in about 1 per 1,000 births[1] and results in about 17,000 deaths.[134] 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[135] 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.[94] 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.[1]

Maternal age 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 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.[136]

History

 
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.[137]
 
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.[28][138][139] Édouard Séguin described it as separate from cretinism in 1844.[29][140] 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 Mongolian race, John Langdon Down used the term "mongoloid".[141] He felt that the existence of Down syndrome confirmed that all peoples were genetically related.[142] In the 1950s with discovery of the underlying cause as being related to chromosomes, concerns about the race-based nature of the name increased.[143]

In 1961, a group of nineteen scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term".[144] The World Health Organization (WHO) dropped the term in 1965 after a request by the delegation from the Mongolian People's Republic.[145] While this racist terminology continued to be used until the late twentieth century,[146]: 21  it is now considered unacceptable and is no longer in common use.

In antiquity, many infants with disabilities were either killed or abandoned.[29] 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.[147] 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,[148] and the 16th-century painting The Adoration of the Christ Child.[149][150]

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.[151]

With the discovery of karyotype techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape.[140] In 1959 Jérôme Lejeune reported the discovery that Down syndrome resulted from an extra chromosome.[28] However, Lejeune's claim to the discovery has been disputed,[152] 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.[153] The discovery took place in the laboratory of Raymond Turpin at the Hôpital Trousseau in Paris, France.[154] Jérôme Lejeune and Marthe Gautier were both his students.[155]

As a result of this discovery, the condition became known as trisomy 21.[156] 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.[157]

Society and culture

See also: List of people with Down syndrome

Name

Down syndrome is named after John Langdon Down. He was the first person to provide an accurate description of the syndrome. His research that was published in 1866 earned him the recognition as the Father of the syndrome.[158] While others had previously recognized components of the condition, John Langdon Down described the syndrome as a distinct, unique medical condition.[14]

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".[159] However, both the possessive and nonpossessive forms remain in use by the general population.[160] The term "trisomy 21" is also commonly used.[144][161]

Ethics

 
Father with son who has Down syndrome

Obstetricians routinely offer antenatal screenings for various conditions, including Down syndrome.[162][163] As a medically reasonable procedure, requiring informed consent, people should be given information about it.[162] It will then be the woman's choice, based on her personal beliefs, how much or how little screening she wishes.[164][165] When results from testing become available, it is considered an ethical requirement to share the results with the patient.[162][166]

Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being.[167] One criticism of this reasoning is that it often values those with disabilities less.[168] Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide.[169][170] The disability rights movement does not have a position on screening,[171] although some members consider testing and abortion discriminatory.[171] Some in the United States who are anti-abortion support abortion if the fetus is disabled, while others do not.[172] 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.[172]

Within the US, some Protestant denominations see abortion as acceptable when a fetus has Down syndrome while Orthodox Christianity and Roman Catholicism do not.[173] Some of those against screening refer to it as a form of eugenics.[173] Disagreement exists within Islam regarding the acceptability of abortion in those carrying a fetus with Down syndrome.[174] Some Islamic countries allow abortion, while others do not.[174] Parents may be stigmatized whichever decision they make.[175]

Advocacy groups

Advocacy groups for individuals with Down syndrome began to be formed after the Second World War.[176] 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,[176] as well as groups providing support for families with children living with Down syndrome.[176] 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,[176][177] Kobato Kai founded in Japan in 1964,[176] the National Down Syndrome Congress founded in the United States in 1973 by Kathryn McGee and others,[176][178] and the National Down Syndrome Society founded in 1979 in the United States.[176] The first Roman Catholic order of nuns for women with Down Syndrome, Little Sisters Disciples of the Lamb, was founded in 1985 in France.[179]

The first World Down Syndrome Day was held on 21 March 2006.[180] The day and month were chosen to correspond with 21 and trisomy, respectively.[181] It was recognized by the United Nations General Assembly in 2011.[180]

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.[182] 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.[183][184]

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.[185][186]

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.[187][188]

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.[189]

Despite ongoing advocacy, the issue remains unresolved, and swimmers with Down syndrome continue to face challenges in accessing appropriate classification pathways.[190][191]

Research

See also: Down syndrome research and Mouse models of Down syndrome

Efforts are underway to determine how the extra chromosome 21 material causes Down syndrome, as currently this is unknown,[192] and to develop treatments to improve intelligence in those with the syndrome.[193] Two efforts being studied are the use stem cells[192] and gene therapy.[194][195] Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonists, and memantine.[196] Research is often carried out on an animal model, the Ts65Dn mouse.[197]

Other hominids

Down syndrome may also occur in hominids other than humans. In 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 in 1969 and a Bornean orangutan in 1979, but neither lived very long. The common chimpanzee Kanako (born around 1993, in Japan) has become the longest-lived known example of this condition. 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.[199][200]

In popular culture

 
Chris Burke, an actor with Down syndrome, born in 1965

Individuals

Television and film

Music

See also

Notes

  1. ^ Using the traditional numbering; the current numbering scheme retains human chromosome numbers, using 2A and 2B instead of 2 and 3 to refer to the two chromosomes that fused into chromosome 2 in humans.[198]

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Further reading

  • Thompson SB (2000). "The Central Executive System in people with Down's syndrome and dementia". Clinical Gerontologist. 21 (3). Taylor & Francis (Routledge): 3–32. doi:10.1300/j018v21n03_02. ISSN 1545-2301. OCLC 1106716083. S2CID 218575706.
  • Thompson SB (2000). "Investigation into Down's syndrome and dementia". Journal of the Association of Practitioners in Learning Disability. 17 (3): 10–14.
  • 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:10.1300/j018v20n03_04. ISSN 1545-2301. OCLC 1106716083.
  • Fox N (2021-11-26). . BBC News. Archived from the original on 2021-11-27. Retrieved 2021-11-27.

External links

 
Wikimedia Commons has media related to Down syndrome.
 
Wikiquote has quotations related to Down syndrome.

April 12, 2024
down, syndrome, down, syndrome, also, known, trisomy, genetic, disorder, caused, presence, part, third, copy, chromosome, usually, associated, with, developmental, delays, mild, moderate, intellectual, disability, characteristic, physical, features, there, thr. Down syndrome or Down s syndrome also known as trisomy 21 is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21 3 It is usually associated with developmental delays mild to moderate intellectual disability and characteristic physical features 1 12 There are three types of Down syndrome all with the same features Trisomy 21 the most common type Mosaic Down syndrome and Translocation Down syndrome 13 14 Down syndromeOther namesDown s syndrome Down s trisomy 21An eight year old boy displaying characteristic facial features of Down syndromeSpecialtyMedical genetics pediatricsSymptomsDelayed development characteristic physical features mild to moderate intellectual disability 1 Usual onsetMostly at conception rarely after fertilization 2 DurationLifelongCausesThird copy of chromosome 21 3 Risk factorsOlder age of mother prior affected child 4 5 Diagnostic methodPrenatal screening genetic testing 6 TreatmentPhysical therapy Occupational therapy Speech therapy Educational support Supported work environment 7 8 PrognosisLife expectancy 50 to 60 years developed world 9 10 Frequency5 4 million 0 1 1 11 Named afterJohn Langdon DownThe parents of the affected individual are usually genetically normal 15 The probability increases from less than 0 1 in 20 year old mothers to 3 in those of age 45 4 The extra chromosome is provided at conception as the egg and sperm combine 16 A very small percentage of 1 2 gets the additional chromosome in the embryo stage and it only impacts some of the cells in the body this is known as Mosaic Down syndrome 17 18 Usually babies get 23 chromosomes from each parent for a total of 46 whereas in Down syndrome a third 21st chromosome is attached 18 It is believed to occur by chance with no known behavioral activity or environmental factor that changes the probability 2 Down syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing or after birth by direct observation and genetic testing 6 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 19 20 21 There is no cure for Down syndrome 22 Education and proper care have been shown to provide good quality of life 7 Some children with Down syndrome are educated in typical school classes while others require more specialized education 8 Some individuals with Down syndrome graduate from high school and a few attend post secondary education 23 In adulthood about 20 in the United States do paid work in some capacity 24 with many requiring a sheltered work environment 8 Support in financial and legal matters is often needed 10 Life expectancy is around 50 to 60 years in the developed world with proper health care 9 10 Regular screening for health issues common in Down syndrome is recommended throughout the person s life 9 Down syndrome is the most common chromosomal abnormality 25 It occurs in about 1 in 1 000 babies born each year 1 In the US this figure is given as one in 700 births 13 In 2015 Down syndrome was present in 5 4 million individuals globally and resulted in 27 000 deaths down from 43 000 deaths in 1990 11 26 27 It is named after British physician John Langdon Down who fully described the syndrome in 1866 28 Some aspects of the condition were described earlier by French psychiatrist Jean Etienne Dominique Esquirol in 1838 and French physician Edouard Seguin in 1844 29 The genetic cause of Down syndrome was discovered in 1959 28 Contents 1 Signs and symptoms 1 1 Physical 1 2 Neurological 1 3 Senses 1 4 Heart 1 5 Cancer 1 5 1 Blood cancers 1 5 2 Non blood cancers 1 6 Endocrine 1 7 Gastrointestinal 1 8 Teeth 1 9 Fertility 2 Cause 2 1 Trisomy 21 2 2 Mosaic Down syndrome 2 3 Translocation Down syndrome 3 Mechanism 3 1 Epigenetics 4 Diagnosis 4 1 Screening before birth 4 1 1 Ultrasound 4 1 2 Blood tests 4 1 3 Combinations 4 1 4 Efficacy 4 1 5 Invasive genetic testing 4 2 Abortion rates 4 3 After birth 5 Management 5 1 Health screening 5 2 Cognitive development 5 3 Other 6 Prognosis 7 Epidemiology 8 History 9 Society and culture 9 1 Name 9 2 Ethics 9 3 Advocacy groups 9 4 Paralympic Swimming 10 Research 11 Other hominids 12 In popular culture 12 1 Music 13 See also 14 Notes 15 References 16 Further reading 17 External linksSigns and symptoms nbsp A boy with Down syndrome using a cordless drill to assemble a book caseThose with Down syndrome nearly always have physical and intellectual disabilities 30 As adults their mental abilities are typically similar to those of an 8 or 9 year old 9 At the same time their emotional and social awareness is very high 31 They can have poor immune function 15 and generally reach developmental milestones at a later age 10 They have an increased risk of a number of health concerns such as congenital heart defect epilepsy leukemia and thyroid diseases 28 Characteristics Percentage Characteristics PercentageMental impairment 99 32 Abnormal teeth 60 33 Stunted growth 90 34 Slanted eyes 60 15 Umbilical hernia 90 35 Shortened hands 60 33 Increased skin on back of neck 80 28 Short neck 60 33 Low muscle tone 80 36 Obstructive sleep apnea 60 28 Narrow roof of mouth 76 33 Bent fifth finger tip 57 15 Flat head 75 15 Brushfield spots in the iris 56 15 Flexible ligaments 75 15 Single transverse palmar crease 53 15 Proportionally large tongue 37 75 36 Protruding tongue 47 33 Abnormal outer ears 70 28 Congenital heart disease 40 33 Flattened nose 68 15 Strabismus 35 1 Separation of first and second toes 68 33 Undescended testicles 20 38 Physical nbsp Feet of a boy with Down syndrome showing the deviated first toesPeople with Down syndrome may have these physical characteristics a small chin epicanthic folds low muscle tone a flat nasal bridge a single crease of the palm and a protruding tongue A protruding tongue is caused by low tone and weak facial muscles and often corrected with myofunctional exercises 39 Some characteristic airway features can lead to obstructive sleep apnea in around half of those with Down syndrome 28 Other common features include excessive joint flexibility extra space between big toe and second toe single palm lines and short fingers 33 36 Instability of the atlantoaxial joint occurs in about 1 2 40 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 41 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 41 Growth in height is slower resulting in adults who tend to have short stature the average height for men is 154 cm 5 ft 1 in and for women is 142 cm 4 ft 8 in 42 Individuals with Down syndrome are at increased risk for obesity as they age due to hypothyroidism other medical issues and lifestyle 28 43 Growth charts have been developed specifically for children with Down syndrome 28 Neurological This syndrome causes about a third of cases of intellectual disability 15 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 44 Walking is acquired in 50 of children after 24 months 45 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 1 46 Those with mosaic Down syndrome typically have IQ scores 10 30 points higher than that 47 As they age the gap tends to widen between people with Down syndrome and their same age peers 46 48 Commonly individuals with Down syndrome have better language understanding than ability to speak 28 46 Babbling typically emerges around 15 months on average 49 10 45 of those with Down syndrome have either a stutter or rapid and irregular speech making it difficult to understand them 50 After reaching 30 years of age some may lose their ability to speak 9 They typically do fairly well with social skills 28 Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability 46 In children with Down syndrome mental illness occurs in nearly 30 with autism occurring in 5 10 10 People with Down syndrome experience a wide range of emotions 51 While people with Down syndrome are generally happy 52 symptoms of depression and anxiety may develop in early adulthood 9 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 9 This includes an increased risk of a specific type of seizure called infantile spasms 28 Many 15 who live 40 years or longer develop Alzheimer s disease 53 In those who reach 60 years of age 50 70 have the disease 9 Senses nbsp Brushfield spots visible in the irises of a baby with Down syndromeHearing and vision disorders occur in more than half of people with Down syndrome 28 Vision problems occur in 38 80 of cases 1 Between 20 and 50 have strabismus in which the two eyes do not move together 1 Cataracts cloudiness of the lens of the eye occur in 15 10 and may be present at birth 1 Keratoconus a thin cone shaped cornea 9 and glaucoma increased eye pressure are also more common 1 as are refractive errors requiring glasses or contacts 9 Brushfield spots small white or grayish brown spots on the outer part of the iris are present in 38 85 of individuals 1 Hearing problems are found in 50 90 of children with Down syndrome 54 This is often the result of otitis media with effusion which occurs in 50 70 10 and chronic ear infections which occur in 40 60 55 Ear infections often begin in the first year of life and are partly due to poor eustachian tube function 56 57 Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal 9 Even a mild degree of hearing loss can have negative consequences for speech language understanding and academics 1 57 It is important to rule out hearing loss as a factor in social and cognitive deterioration 58 Age related hearing loss of the sensorineural type occurs at a much earlier age and affects 10 70 of people with Down syndrome 9 Heart The rate of congenital heart disease in newborns with Down syndrome is around 40 33 Of those with heart disease about 80 have an atrial septal defect or ventricular septal defect with the former being more common 9 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 59 Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development endothelial dysfunction and proinflammatory genes 59 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 and patent ductus arteriosus 56 People with Down syndrome have a lower risk of hardening of the arteries 9 Cancer Although the overall risk of cancer in Down syndrome is not changed 60 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 9 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 61 In 2008 the World Health Organization WHO introduced a distinct classification for myeloid proliferation in individuals with Down syndrome 62 Blood cancers Leukemia is 10 to 15 times more common in children with Down syndrome 28 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 63 Acute megakaryoblastic leukemia AMKL is a leukemia of megakaryoblasts the precursors cells to megakaryocytes which form blood platelets 63 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 63 64 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 65 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 66 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 63 67 GATA1 mutations combined with Trisomy 21 contribute to a predisposition to Transient Abnormal Myelopoiesis TAM 68 In Trisomy 21 the process of leukemogenesis starts in early fetal life with genetic factors including GATA1 mutations contributing to the development of Transient Abnormal Myelopoiesis TAM on the preleukemic pathway 66 The condition affects 3 10 of babies with Down 63 While it often spontaneously resolves within three months of birth it can cause serious blood liver or other complications 69 In about 10 of cases TMD progresses to AMKL during the three months to five years following its resolution 63 69 68 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 61 This low risk is thought to be due to an increase in the expression of tumor suppressor genes present on chromosome 21 70 61 One exception is testicular germ cell cancer which occurs at a higher rate in Down syndrome 61 Endocrine Problems of the thyroid gland occur in 20 50 of individuals with Down syndrome 9 28 Low thyroid 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 which occurs in 1 10 or can develop later due to an attack on the thyroid by the immune system resulting in Graves disease or autoimmune hypothyroidism 71 Type 1 diabetes mellitus is also more common 9 Gastrointestinal Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior 28 One potential cause is Hirschsprung s disease occurring in 2 15 which is due to a lack of nerve cells controlling the colon 72 Other congenital problems can include duodenal atresia imperforate anus and gastroesophageal reflux disease 56 Celiac disease affects about 7 20 9 28 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 73 74 While plaque and poor oral hygiene are contributing factors the severity of these periodontal diseases cannot be explained solely by external factors 74 Research suggests that the severity is likely a result of a weakened immune system 74 75 The weakened immune system also contributes to increased incidence of yeast infections in the mouth from Candida albicans 75 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 76 less effective oral hygiene habits and higher plaque indexes 73 75 76 77 Higher rates of tooth wear and bruxism are also common 75 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 73 75 76 77 Less common manifestations include cleft lip and palate and enamel hypocalcification 20 prevalence 77 Taurodontism an elongation of the pulp chamber has a high prevalence in people with DS 78 79 Fertility Males with Down syndrome usually do not father children while females have lower rates of fertility relative to those who are unaffected 80 Fertility is estimated to be present in 30 50 of females 81 Menopause usually occurs at an earlier age 9 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 80 As of 2006 three instances of males with Down syndrome fathering children and 26 cases of females having children have been reported 80 Without assisted reproductive technologies around half of the children of someone with Down syndrome will also have the syndrome 80 82 CauseMain article Genetics of Down syndromeThe cause of the extra full or partial chromosome is still unknown 83 Most of the time Down syndrome is caused by a random mistake in cell division during early development of the fetus but not inherited 84 and there is no scientific research which shows that environmental factors or the parents activities contribute to Down syndrome The only factor that has been linked to the increased chance of having a baby with Down syndrome is advanced parental age This is mostly associated with advanced maternal age but about 10 per cent of cases are associated with advanced paternal age 85 nbsp Karyotype for Down syndrome trisomy 21 showing the three copies of chromosome 21Down syndrome is caused by having three copies of the genes on chromosome 21 rather than the usual two 3 86 The parents of the affected individual are typically genetically normal 15 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 81 The extra chromosome content can arise through several different ways The most common cause about 92 95 of cases is a complete extra copy of chromosome 21 resulting in trisomy 21 82 87 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 81 88 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 28 81 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 82 Trisomy 21 Down syndrome also known by the karyotype 47 XX 21 for females and 47 XY 21 for males 89 is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development known as nondisjunction 82 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 82 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 90 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 13 This type is the least common form of Down syndrome and accounts for only about 1 of all cases 83 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 13 Translocation Down syndrome The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2 4 of cases 81 91 In this translocation Down syndrome the long arm of chromosome 21 is attached to another chromosome often chromosome 14 92 In a male affected with Down syndrome it results in a karyotype of 46XY t 14q21q 92 93 This may be a new mutation or previously present in one of the parents 94 The parent with such a translocation is usually normal physically and mentally 92 however during production of egg or sperm cells a higher chance of creating reproductive cells with extra chromosome 21 material exists 91 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 94 The probability of this type of Down syndrome is not related to the mother s age 92 Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome 92 In this case it is sometimes known as familial Down syndrome 95 MechanismThe extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21 86 This overexpression has been estimated at 50 due to the third copy of the chromosome present 81 Some research has suggested the Down syndrome critical region is located at bands 21q22 1 q22 3 96 with this area including genes for the amyloid precursor protein superoxide dismutase and likely the ETS2 proto oncogene 97 Other research however has not confirmed these findings 86 MicroRNAs are also proposed to be involved 98 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 99 Amyloid beta is processed from amyloid precursor protein the gene for which is located on chromosome 21 99 Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age though dementia may not be present 15 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 28 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 100 DiagnosisScreening before birth Guidelines recommend screening for Down syndrome to be offered to all pregnant women regardless of age 101 102 A number of tests are used with varying levels of accuracy They are typically used in combination to increase the detection rate 28 None can be definitive thus if screening is positive either amniocentesis or chorionic villus sampling is required to confirm the diagnosis 101 When screening tests predict a high possibility of Down syndrome a more invasive diagnostic test amniocentesis or chorionic villus sampling is needed to confirm the diagnosis 101 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 103 The presence or absence of many markers is more accurate 103 Increased fetal nuchal translucency NT indicates an increased possibility of Down syndrome picking up 75 80 of cases and being falsely positive in 6 104 nbsp Ultrasound of fetus with Down syndrome showing a large bladder nbsp Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndromeBlood tests Several blood markers can be measured to predict the chances of Down syndrome during the first or second trimester 105 106 Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results 105 In the second trimester often two or three tests are used in combination with two or three of a fetoprotein unconjugated estriol total hCG and free bhCG detecting about 60 70 of cases 106 Testing of the mother s blood for fetal DNA is being studied and appears promising in the first trimester 107 108 The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high likelihood of trisomy 21 109 Accuracy has been reported at 98 6 in the first trimester of pregnancy 28 Confirmatory testing by invasive techniques amniocentesis CVS is still required to confirm the screening result 109 Combinations First and second trimester screening 101 Screen Week of pregnancy when performed Detection rate False positive DescriptionCombined 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 AQuad screen 15 20 wks 81 5 Measures the maternal serum alpha fetoprotein unconjugated estriol hCG and inhibin AIntegrated test 15 20 wks 94 96 5 Is a combination of the quad screen PAPP A and NTCell free fetal DNA From 10 wks 110 96 100 107 0 3 111 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 101 The different screening techniques in use are able to pick up 90 95 of cases with a false positive rate of 2 5 105 If Down syndrome occurs in one in 500 pregnancies with a 90 detection rate and the test used has a 5 false positive rate this means of 20 women who test positive on screening only one will not have a fetus with Down syndrome confirmed 105 If the screening test has a 2 false positive rate this means of 50 women who test positive on screening one will not have a fetus with Down syndrome 105 Invasive genetic testing Amniocentesis and chorionic villus sampling are more reliable tests but they increase the risk of miscarriage by between 0 5 1 112 The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks 112 nbsp An example of an algorithm for determining the indication for prenatal genetic testing of Down syndrome 113 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 112 Abortion rates About 92 of pregnancies in Europe with a diagnosis of Down syndrome are terminated 21 As a result there is almost no one with Down syndrome in Iceland and Denmark where screening is commonplace 114 In the United States the termination rate after diagnosis is around 75 114 but varies from 61 to 93 depending on the population surveyed 20 Rates are lower among women who are younger and have decreased over time 20 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 115 After birth The diagnosis can often be suspected based on the child s physical appearance at birth 10 Informing the parents of a diagnosis needs to be made as soon as possible with care and sensitivity Even an uncertain diagnosis needs to be informed of in the same way 116 This allows for a longer time for processing the information 116 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 10 ManagementEfforts 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 117 Education and proper care can provide a positive quality of life 7 Typical childhood vaccinations are recommended 28 Health screening Recommended screening Testing Children 118 Adults 9 Hearing 6 months 12 months then yearly 3 5 yearsT4 and TSH 6 months then yearlyEyes 6 months then yearly 3 5 yearsTeeth 2 years then every 6 monthsCeliac disease Between 2 and 3 years of age or earlier if symptoms occurSleep study 3 to 4 years or earlier if symptoms of obstructive sleep apnea occurNeck X rays Between 3 and 5 years of ageA number of health organizations have issued recommendations for screening those with Down syndrome for particular diseases 118 This is recommended to be done systematically 28 At birth all children should get an electrocardiogram and ultrasound of the heart 28 Surgical repair of heart problems may be required as early as three months of age 28 Heart valve problems may occur in young adults and further ultrasound evaluation may be needed in adolescents and in early adulthood 28 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 or other amplification devices can be useful for language learning 28 Speech therapy may be useful and is recommended to be started around nine months of age 28 As those with Down syndrome typically have good hand eye coordination learning sign language is a helpful communication tool 46 Augmentative and alternative communication methods such as pointing body language objects or pictures are often used to help with communication 119 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 whereby students of differing abilities are placed in classes with their peers of the same age provided some adjustments are made to the curriculum 120 In the United States the Individuals with Disabilities Education Act of 1975 requires public schools generally to allow attendance by students with Down syndrome 121 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 122 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 123 Other Tympanostomy tubes are often needed 28 and often more than one set during the person s childhood 54 Tonsillectomy is also often done to help with sleep apnea and throat infections 28 Surgery does not correct every instance of sleep apnea and a continuous positive airway pressure CPAP machine may be useful in those cases 54 Efforts to prevent respiratory syncytial virus RSV infection with human monoclonal antibodies should be considered especially in those with heart problems 1 In those who develop dementia there is no evidence for memantine 124 donepezil 125 rivastigmine 126 or galantamine 127 Prognosis nbsp Deaths due to Down syndrome per million persons in 2012 0 1 2 3 4 5 6 7 8 9 16Between 5 15 of children with Down syndrome in Sweden attend regular school 128 Some graduate from high school however most do not 23 Of those with intellectual disability in the United States who attended high school about 40 graduated 129 Many learn to read and write and some are able to do paid work 23 In adulthood about 20 in the United States do paid work in some capacity 24 130 In Sweden however less than 1 have regular jobs 128 Many are able to live semi independently 15 but they often require help with financial medical and legal matters 10 Those with mosaic Down syndrome usually have better outcomes 81 Individuals with Down syndrome have a higher risk of early death than the general population 28 This is most often from heart problems or infections 1 9 Following improved medical care particularly for heart and gastrointestinal problems the life expectancy has increased 1 This increase has been from 12 years in 1912 131 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 69 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 15 In those without heart problems 85 studied survived to at least 10 years and 80 survived to at least 30 years of age 15 It is estimated that 10 lived to 70 years of age in the early 2000s 82 Much of this data is outdated and life expectancy has drastically improved with more equitable healthcare and continuous advancement of surgical practice 132 The National Down Syndrome Society provides information regarding raising a child with Down syndrome 133 Epidemiology nbsp The risk of having a Down syndrome pregnancy in relation to a mother s age 4 Down syndrome is the most common chromosomal abnormality in humans 9 Globally as of 2010 update Down syndrome occurs in about 1 per 1 000 births 1 and results in about 17 000 deaths 134 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 135 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 94 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 1 Maternal age 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 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 136 History nbsp 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 137 nbsp John Langdon Haydon Down first described Down syndromeEnglish 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 28 138 139 Edouard Seguin described it as separate from cretinism in 1844 29 140 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 Mongolian race John Langdon Down used the term mongoloid 141 He felt that the existence of Down syndrome confirmed that all peoples were genetically related 142 In the 1950s with discovery of the underlying cause as being related to chromosomes concerns about the race based nature of the name increased 143 In 1961 a group of nineteen scientists suggested that mongolism had misleading connotations and had become an embarrassing term 144 The World Health Organization WHO dropped the term in 1965 after a request by the delegation from the Mongolian People s Republic 145 While this racist terminology continued to be used until the late twentieth century 146 21 it is now considered unacceptable and is no longer in common use In antiquity many infants with disabilities were either killed or abandoned 29 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 147 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 148 and the 16th century painting The Adoration of the Christ Child 149 150 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 151 With the discovery of karyotype techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape 140 In 1959 Jerome Lejeune reported the discovery that Down syndrome resulted from an extra chromosome 28 However Lejeune s claim to the discovery has been disputed 152 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 153 The discovery took place in the laboratory of Raymond Turpin at the Hopital Trousseau in Paris France 154 Jerome Lejeune and Marthe Gautier were both his students 155 As a result of this discovery the condition became known as trisomy 21 156 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 157 Society and cultureSee also List of people with Down syndrome Name Down syndrome is named after John Langdon Down He was the first person to provide an accurate description of the syndrome His research that was published in 1866 earned him the recognition as the Father of the syndrome 158 While others had previously recognized components of the condition John Langdon Down described the syndrome as a distinct unique medical condition 14 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 159 However both the possessive and nonpossessive forms remain in use by the general population 160 The term trisomy 21 is also commonly used 144 161 Ethics nbsp Father with son who has Down syndromeObstetricians routinely offer antenatal screenings for various conditions including Down syndrome 162 163 As a medically reasonable procedure requiring informed consent people should be given information about it 162 It will then be the woman s choice based on her personal beliefs how much or how little screening she wishes 164 165 When results from testing become available it is considered an ethical requirement to share the results with the patient 162 166 Some bioethicists deem it reasonable for parents to select a child who would have the highest well being 167 One criticism of this reasoning is that it often values those with disabilities less 168 Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide 169 170 The disability rights movement does not have a position on screening 171 although some members consider testing and abortion discriminatory 171 Some in the United States who are anti abortion support abortion if the fetus is disabled while others do not 172 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 172 Within the US some Protestant denominations see abortion as acceptable when a fetus has Down syndrome while Orthodox Christianity and Roman Catholicism do not 173 Some of those against screening refer to it as a form of eugenics 173 Disagreement exists within Islam regarding the acceptability of abortion in those carrying a fetus with Down syndrome 174 Some Islamic countries allow abortion while others do not 174 Parents may be stigmatized whichever decision they make 175 Advocacy groups Advocacy groups for individuals with Down syndrome began to be formed after the Second World War 176 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 176 as well as groups providing support for families with children living with Down syndrome 176 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 176 177 Kobato Kai founded in Japan in 1964 176 the National Down Syndrome Congress founded in the United States in 1973 by Kathryn McGee and others 176 178 and the National Down Syndrome Society founded in 1979 in the United States 176 The first Roman Catholic order of nuns for women with Down Syndrome Little Sisters Disciples of the Lamb was founded in 1985 in France 179 The first World Down Syndrome Day was held on 21 March 2006 180 The day and month were chosen to correspond with 21 and trisomy respectively 181 It was recognized by the United Nations General Assembly in 2011 180 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 182 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 183 184 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 185 186 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 187 188 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 189 Despite ongoing advocacy the issue remains unresolved and swimmers with Down syndrome continue to face challenges in accessing appropriate classification pathways 190 191 ResearchSee also Down syndrome research and Mouse models of Down syndrome Efforts are underway to determine how the extra chromosome 21 material causes Down syndrome as currently this is unknown 192 and to develop treatments to improve intelligence in those with the syndrome 193 Two efforts being studied are the use stem cells 192 and gene therapy 194 195 Other methods being studied include the use of antioxidants gamma secretase inhibition adrenergic agonists and memantine 196 Research is often carried out on an animal model the Ts65Dn mouse 197 Other hominidsDown syndrome may also occur in hominids other than humans In 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 in 1969 and a Bornean orangutan in 1979 but neither lived very long The common chimpanzee Kanako born around 1993 in Japan has become the longest lived known example of this condition 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 199 200 In popular culture nbsp Chris Burke an actor with Down syndrome born in 1965IndividualsJamie Brewer is an American actress and model She is best known for her roles in the FX horror anthology television series American Horror Story 201 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 202 Sofia Jirau is a Puerto Rican model with Down syndrome working with top designers and renowned media outlets such Vogue Mexico People Hola among others 203 204 205 In February 2020 Jirau made her debut at New York Fashion Week 206 Then in February 2022 she became the first ever model with Down Syndrome to be hired by the American retail company Victoria s Secret 207 She walked the LA Fashion Week runway in 2022 208 Jirau launched a campaign in 2021 called Sin Limites 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 208 Chris Nikic is the first person with Down syndrome to finish an Ironman Triathlon 209 He was awarded the Jimmy V Award for Perseverance at the 2021 ESPY Awards 210 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 211 Grace Strobel is an American model and the first person with Down Syndrome to represent an American skin care brand 212 She first joined Obagi in 2020 and continues to be an Ambassador for the brand as of 2022 213 214 She walked the runway representing Tommy Hilfiger for Runway of Dreams New York Fashion Week 2020 and Atlantic City Fashion Week 215 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 215 216 She is also a public speaker and gives a presentation called TheGraceEffect about what it is like to live with Down syndrome 217 216 Television and film Life Goes On is an American drama television series that aired on ABC from September 12 1989 to May 23 1993 218 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 219 Burke s revolutionary role conveyed a realistic portrayal of people with Down syndrome and changed the way audiences viewed people with disabilities 220 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 4 main actors with Down syndrome Madison Tevlin Kevin Iannucci Matthew Von Der Ahe and James Day Keith 221 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 222 The show received a Television Academy Honor in 2016 223 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 224 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 225 Music The Devo song Mongoloid is about someone with Down syndrome The Amateur Transplants song Your Baby is about a fetus with Down syndrome See alsoList of syndromes Characteristics of syndromic ASD conditionsNotes Using the traditional numbering the current numbering scheme retains human chromosome numbers using 2A and 2B instead of 2 and 3 to refer to the two chromosomes that fused into chromosome 2 in humans 198 References a b c d e f g h i j k l m n o p q r s t Weijerman ME de Winter JP December 2010 Clinical practice The care of children with Down syndrome European Journal of Pediatrics 169 12 1445 1452 doi 10 1007 s00431 010 1253 0 PMC 2962780 PMID 20632187 a b What causes Down syndrome National Institute of Child Health and Human Development U S National Institutes of Health 2014 01 17 Archived from the original on 5 January 2016 Retrieved 6 January 2016 a b c d Patterson D July 2009 Molecular genetic analysis of Down syndrome Human Genetics 126 1 195 214 doi 10 1007 s00439 009 0696 8 PMID 19526251 S2CID 10403507 a b c d e f Morris 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and neurodegenerative components of Down syndrome Developmental Neuroscience 33 5 414 427 doi 10 1159 000330861 PMC 3254040 PMID 21893967 Sansom C October 2015 The evolution of human chromosome 2 PDF The Biochemist 37 5 40 41 doi 10 1042 BIO03705040 Hirata S Hirai H Nogami E Morimura N Udono T April 2017 Chimpanzee Down syndrome a case study of trisomy 22 in a captive chimpanzee Primates Journal of Primatology 58 2 Springer 267 273 doi 10 1007 s10329 017 0597 8 eISSN 1610 7365 hdl 2433 228259 LCCN sf80001417 OCLC 51531954 PMID 28220267 S2CID 5536021 Hays B Second case of Down syndrome in chimpanzees identified in Japan UPI Retrieved 11 May 2019 Lawton A 2011 11 21 Interview with Jamie Brewer MediaMikes Retrieved 2023 04 01 Probus S McNeal J 12 February 2015 Meet The First Woman With Down Syndrome To Walk At Fashion Week BuzzFeed News Retrieved 2023 04 01 Puerto Rican model with Down Syndrome Sofia Jirau is conquering the fashion world HOLA 2020 02 19 Retrieved 2023 04 01 Mier T 17 February 2020 NYFW Model with Down Syndrome Says There Are No Limits Peoplemag Retrieved 2023 04 01 Sofia Jirau la modelo latina con sindrome de down que decanto en el Fashion Week de Nueva York Vogue in Mexican Spanish 2020 02 13 Retrieved 2023 04 01 V J Latina Model With Down Syndrome Walks at New York Fashion Week The Mighty Retrieved 2023 04 01 Holender S 2022 02 17 Meet Sofia Jirau Victoria s Secret s 1st Model With Down Syndrome Us Weekly Retrieved 2023 04 01 a b About me Sofia Jirau Model Retrieved 2023 04 01 Nikic becomes first person with Down s syndrome to finish Ironman BBC Sport Retrieved 2023 04 01 2021 ESPYS award winners ESPN com 2021 07 10 Retrieved 2023 04 01 About Chris Nikic chrisnikic com Retrieved 2023 04 01 Abelman D 21 March 2021 Grace Strobel Knows How Good Her Skin Looks Allure Retrieved 2023 04 01 Obagi Obagi Announces Partnership with Down Syndrome Advocate Grace Strobel as new SKINCLUSION Ambassador and Face of New Obagi Clinical Cleanser www prnewswire com Press release Retrieved 2023 04 01 Obagi Obagi Clinical Continues Collaboration with Down Syndrome Advocate Grace Strobel www prnewswire com Press release Retrieved 2023 04 01 a b LeBlanc DA March 2022 The Grace Effect Local model is on a mission to change the world in style WestNewsMagazine com Retrieved 2023 04 01 a b Strobel G 2020 01 24 TheGraceEffect Creating Ripples With Kindness And Respect Channel Kindness Retrieved 2023 04 01 Down syndrome advocate Grace Strobel on pushing boundaries Let no one tell you what you can and cannot achieve Yahoo Life 21 March 2022 Retrieved 2023 04 01 Life Goes On TV Series 1989 1993 IMDb retrieved 2023 04 01 Life Goes On Actor Chris Burke on Being the First Primetime Television Star with Down Syndrome Oprah com Archived from the original on 14 August 2015 Retrieved 2023 04 01 Randle N 1990 12 20 Our Ticket to Acceptance Actor With Down s Syndrome on Life Goes On Has Become Role Model for Many Los Angeles Times Retrieved 2023 04 01 Champions 2023 IMDb retrieved 2023 04 01 Born This Way Television Academy Retrieved 2023 04 01 Heasley S 2015 11 16 New TV Series Features Young Adults With Down Syndrome Disability Scoop Retrieved 2023 04 01 The Peanut Butter Falcon 2019 IMDb retrieved 2023 04 01 The Peanut Butter Falcon Lionsgate Retrieved 1 April 2023 Further readingThompson SB 2000 The Central Executive System in people with Down s syndrome and dementia Clinical Gerontologist 21 3 Taylor amp Francis Routledge 3 32 doi 10 1300 j018v21n03 02 ISSN 1545 2301 OCLC 1106716083 S2CID 218575706 Thompson SB 2000 Investigation into Down s syndrome and dementia Journal of the Association of Practitioners in Learning Disability 17 3 10 14 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 amp Francis Routledge 23 44 doi 10 1300 j018v20n03 04 ISSN 1545 2301 OCLC 1106716083 Fox N 2021 11 26 World leading Down s syndrome bill clears first hurdle in Parliament BBC News Archived from the original on 2021 11 27 Retrieved 2021 11 27 External links nbsp Wikimedia Commons has media related to Down syndrome nbsp Wikiquote has quotations related to Down syndrome Down syndrome at Curlie Down s syndrome by the UK National Health Service Retrieved from https en wikipedia org w index php title Down syndrome amp oldid 1218451337, wikipedia, wiki, book, books, library,

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