Down syndrome

Those with Down syndrome nearly always have physical and intellectual disabilities. As adults, their mental abilities are typically similar to those of an eight- or nine-year-old. They can have poor immune function Some characteristic airway features can lead to obstructive sleep apnea in around half of those with Down syndrome. Atlantoaxial instability may cause myelopathy due to cervical spinal cord compression later in life, this often manifests as new onset weakness, problems with co-ordination, bowel or bladder incontinence, and gait dysfunction. 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. Individuals with Down syndrome are at increased risk for obesity as they age due to increased risk of hypothyroidism, other medical issues and lifestyle. Growth charts have been developed specifically for children with Down syndrome. Walking is acquired in 50% of children after 24 months. 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. Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that. As they age, the gap tends to widen between people with Down syndrome and their same-age peers. Commonly, individuals with Down syndrome have better language understanding than ability to speak. 10–45% of those with Down syndrome have either a stutter or rapid and irregular speech, making it difficult to understand them. After reaching 30 years of age, some may lose their ability to speak. While people with Down syndrome are generally happy, symptoms of depression and anxiety may develop in early adulthood. In those who reach 60 years of age, 50–70% have the disease. It primarily appears in teenagers and younger adults. Senses , visible in the irises of a baby with Down syndrome Hearing and vision disorders occur in more than half of people with Down syndrome. especially in the Western World. Dot-like opacities in the cortex of the lens (cerulean cataract) are present in up to 50% of people with Down syndrome, but may be followed without treatment if they are not visually significant. In Down syndrome, the presence of epicanthal folds may give the false impression of strabismus, referred to as pseudostrabismus. Nasolacrimal duct obstruction, which causes tearing (epiphora), is more frequently bilateral and multifactorial than in children without Down syndrome. causing visual blurring or distortion. Keratoconus first presents in the teen years and progresses into the thirties. Down syndrome is a strong risk factor for developing keratoconus, and onset may be occur at a younger age than in those without Down syndrome. and may be present at birth. Ear infections often begin in the first year of life and are partly due to poor eustachian tube function. Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal. Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome. Some of the genetic contributions to pulmonary hypertension in individuals with Down syndrome are abnormal lung development, endothelial dysfunction, and proinflammatory genes. People with Down syndrome have a lower risk of hardening of the arteries. 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. Blood cancers Leukemia is 10 to 15 times more common in children with Down syndrome. AMKL is a leukemia of megakaryoblasts, the precursors cells to megakaryocytes which form blood platelets. ALL in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a white blood cell count 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. In short, the likelihood of developing AML and ALL is higher in children with Down syndrome compared to those without Down syndrome. 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. 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. GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM. In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution. 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. One exception is testicular germ cell cancer which occurs at a higher rate in Down syndrome. Type 1 diabetes mellitus is also more common. Other congenital problems can include duodenal atresia, imperforate anus and gastroesophageal reflux disease. While plaque and poor oral hygiene are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors. The weakened immune system also contributes to increased incidence of yeast infections in the mouth (from Candida albicans). less effective oral hygiene habits, and higher plaque indexes. Higher rates of tooth wear and bruxism are also common. Fertility Males with Down syndrome usually do not father children, while females have lower rates of fertility relative to those who are unaffected. Without assisted reproductive technologies, around half of the children of someone with Down syndrome will also have the syndrome. ==Cause==

Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two. The parents of the affected individual are typically genetically normal. 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. 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. Trisomy 21 The trisomy 21 version of Down syndrome (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males) is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development, known as nondisjunction. The root cause of the extra full or partial chromosome is still unknown. The mechanism is not inherited. There is no scientific research which shows that environmental factors or the parents' activities contribute to Down syndrome. The only factor that has been linked to the increased chance of having a baby with Down syndrome is advanced parental age. This is mostly associated with advanced maternal age but about 10 per cent of cases are associated with advanced paternal age. for Down syndrome (trisomy 21) showing the three copies of chromosome 21 Translocation Down syndrome The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% of cases. This may be a new mutation or previously present in one of the parents. 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. 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. 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. ==Mechanism==

The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21. with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene. Other research, however, has not confirmed these findings. 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. Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age, though dementia may not be present. ==Diagnosis==

Screening before birth Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age. A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate. The presence or absence of many markers is more accurate. T21.JPG|Ultrasound of fetus with Down syndrome showing a large bladder Nuchal edema in Down Syndrome Dr. W. Moroder.jpg|Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndrome Blood tests Several blood markers can be measured to predict the chances of Down syndrome during the first or second trimester. Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester. 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. Combinations 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. If Down syndrome occurs in one in 500 pregnancies with a 90% detection rate and the test used has a 5% false-positive rate, of 28 women who test positive on screening, only one will have a fetus with Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means of 11 women who test positive on screening, only one will have a fetus with Down syndrome. The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks. 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. In the United States, the termination rate after diagnosis is around 75%, After birth A diagnosis can often be suspected based on the child's physical appearance at birth. 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. ==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. Education and proper care can provide a positive quality of life. Behavioral issues and mental illness are typically managed with counseling or medications. In the United States, the Individuals with Disabilities Education Act of 1975 requires public schools generally to allow attendance by students with Down syndrome. 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. 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. Physical therapy Therapeutic exercise helps individuals with Down syndrome improve muscle strength, balance, coordination, and gait. Therapeutic exercise is widely used to improve motor function. Interventions typically include aerobic training, resistance (strength) training, balance exercises, and neuromuscular activities. These programs are often structured with specific parameters such as frequency, intensity, and duration to target functional outcomes. A 2023 systematic review and meta-analysis found that combined aerobic and resistance training significantly improves muscle strength in both upper and lower extremities, while aerobic exercise improves gait parameters and dynamic balance. Improvements in these areas may enhance functional mobility and the ability to perform activities of daily living. However, the overall certainty of evidence is considered low to moderate. For children ages 0-3, there is some evidence that therapeutic exercises such as aerobic treadmill training may help gait and motor development. Other Tympanostomy tubes are often needed Tonsillectomy is also often done to help with sleep apnea and throat infections. donepezil, rivastigmine, or galantamine. ==Prognosis==

Between 5–15% of children with Down syndrome in Sweden attend regular school. Many learn to read and write and some are able to do paid work. In Sweden, however, less than 1% have regular jobs. Many are able to live semi-independently, Individuals with Down syndrome have a higher risk of early death than the general population. to 25 years in the 1980s, The National Down Syndrome Society provides information regarding raising a child with Down syndrome. ==Epidemiology==

Down syndrome is the most common chromosomal abnormality in humans. 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. and 1.1 per 1,000 live births in Norway are affected. The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting. ==History==

, The Adoration of the Christ Child, depicts a person with Down syndrome as one of the angels. — first described Down syndrome The English physician John Langdon Down first described Down syndrome in 1862, recognizing it as a distinct type of mental disability, and again in a more widely published report in 1866. Édouard Séguin described it as separate from cretinism in 1844. By the 20th century, Down syndrome had become the most recognizable form of mental disability. Due to his perception that children with Down syndrome shared facial similarities with those of Blumenbach's Mongoloid race, John Langdon Down used the term "Mongoloid". Down felt that the symptoms of Down syndrome in Europeans provided evidence that all peoples were genetically related: In the 1950s with discovery of the underlying cause as being related to chromosomes, concerns about the race-based nature of the name increased. In 1961, a group of nineteen scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term". While this terminology continued to be used until the late twentieth century, it is now considered unacceptable and is no longer in common use. In antiquity, many infants with disabilities were either killed or abandoned. 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, and the 16th-century painting The Adoration of the Christ Child. In the 20th century, many people with Down syndrome were institutionalized, few of the associated medical problems were treated, and most people died in infancy or early adulthood. With the rise of the eugenics movement, 33 of the then 48 US 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. With the discovery of karyotype techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape. 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. The discovery took place in the laboratory of Raymond Turpin at the Hôpital Trousseau in Paris, France. Jérôme Lejeune and Marthe Gautier were both his students. As a result of this discovery, the condition became known as trisomy 21, especially in European countries. 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. ==Society and culture==

Name Down syndrome is named after John Langdon Down. He was the first person to provide an accurate description of the syndrome. His research that was published in 1866 earned him the recognition as the Father of the syndrome. While others had previously recognized components of the condition, John Langdon Down described the syndrome as a distinct, unique medical condition. However, both the possessive and nonpossessive forms remain in use by the general population, and in the United Kingdom the NHS uses the term ''Down's syndrome'' in its patient-oriented information. The term "trisomy 21" is also commonly used. Ethics Obstetricians routinely offer antenatal screenings for various conditions, including Down syndrome. When results from testing become available, it is considered an ethical requirement to share the results with the patient. Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being. One criticism of this reasoning is that it often values those with disabilities less. Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide. The disability rights movement does not have a position on screening, Some in the United States who are anti-abortion support abortion if the fetus is disabled, while others do not. 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. Women may face disapproval whether they choose abortion or not. Some of those against screening refer to it as a form of eugenics. 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, Kobato Kai founded in Japan in 1964, and the National Down Syndrome Society founded in 1979 in the United States. The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy, respectively. It was recognized by the United Nations General Assembly in 2011. 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. 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. 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. Despite ongoing advocacy, the issue remains unresolved, and swimmers with Down syndrome continue to face challenges in accessing appropriate classification pathways. ==Research==

The additional copy of chromosome 21 affects the regulation of other genes, creating a complex set of changes. Mechanisms connecting the genetic defect to pathology remain unclear. While applying gene therapy seems like a promising approach, tailored treatments may be required. Gene therapy delivered via stem cells has been proposed as a tool for studying the syndrome and as an approach to therapy. Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonists, and memantine. Research is often carried out on an animal model, the Ts65Dn mouse. Some research seeks to develop appropriate screening tools to determine appropriate treatment strategies should they prove successful. ==Other hominids==

Down syndrome may also occur in hominids other than humans. In great apes chromosome 22 corresponds to the human chromosome 21 and thus trisomy 22 causes Down syndrome in apes. The condition was observed in a common chimpanzee in 1969 and a Bornean orangutan in 1979, but neither lived very long. The common chimpanzee Kanako, born around 1993 in Japan, was genetically tested and found to have chimpanzee trisomy 22 in 2011. Kanako has some of the same symptoms that are common in human Down syndrome. It is unknown how common this condition is in chimps, but it is plausible it could be roughly as common as Down syndrome is in humans. Kanako was blind, relatively small, and targeted by aggressive group mates. Kanako died in the Kumamoto Sanctuary at Kyoto University in 2020. Fossilized remains of a Neanderthal aged approximately 6 at death were described in 2024. The child, nicknamed Tina, suffered from a malformation of the inner ear that only occurs in people with Down syndrome, and would have caused hearing loss and disabling vertigo. The fact that a Neanderthal with such a condition survived to such an age was taken as evidence of compassion and extra-maternal care among Neanderthals. ==In popular culture==

, an actor with Down syndrome, born in 1965 Individuals • Jamie Brewer is an American actress and model. She is best known for her roles in the FX horror anthology television series American Horror Story. 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. • Tommy Jessop is a British actor, author and activist. He starred in the BAFTA-nominated dramas Coming Down the Mountain and Line of Duty, and was the first person with Down syndrome to play Hamlet professionally as part of a touring production with Blue Apple Theatre. Jessop is a prominent campaigner in the UK and was a key figure in the creation of the Down Syndrome Act 2022. In 2023 Headline Publishing Group published Jessop's autobiography A Life Worth Living: Acting, Activism and Everything Else. • Sofía Jirau is a Puerto Rican model with Down syndrome, working with designers and media outlets such as Vogue Mexico, People, and Hola!. In February 2020, Jirau made her debut at New York Fashion Week. Then in February 2022, she became the first-ever model with Down Syndrome to be hired by the American retail company Victoria's Secret. She walked the LA Fashion Week runway in 2022. Jirau launched a campaign in 2021 called Sin Límites or No Limits "which seeks to make visible the challenges facing the Down syndrome community, demonstrate our ability to achieve our goals, and raise awareness about the condition throughout the world." He was awarded the Jimmy V Award for Perseverance at the 2021 ESPY Awards. 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. • Grace Strobel is an American model and the first person with Down syndrome to represent an American skin-care brand. She first joined Obagi in 2020, and continues to be an Ambassador for the brand as of 2022. She walked the runway representing Tommy Hilfiger for Runway of Dreams New York Fashion Week 2020 and Atlantic City Fashion Week. 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. Television and film • Life Goes On is an American drama television series that aired on ABC from 12 September 1989, to 23 May 1993. 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. Burke's revolutionary role conveyed a realistic portrayal of people with Down syndrome and changed the way audiences viewed people with disabilities. • Champions (2023) is a film starring four main actors with Down syndrome: Madison Tevlin, Kevin Iannucci, Matthew Von Der Ahe and James Day Keith. 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. The show received a Television Academy Honor in 2016. • 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. 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. Music • The Devo song "Mongoloid" is about someone with Down syndrome. • The Amateur Transplants song "Your Baby" is about a fetus with Down syndrome. Toys • In 2023, Mattel released a Barbie doll with characteristics of a person having Down syndrome as a way to promote diversity. ==See also==