[10] They have an increased risk of a number of health concerns, such as congenital heart defect, epilepsy, leukemia, and thyroid diseases.

[29] People with Down syndrome may have these physical characteristics: a small chin, epicanthic folds, low muscle tone, a flat nasal bridge, and a protruding tongue.

[41] 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.

[29] Brushfield spots (small white or grayish/brown spots on the periphery of the iris), upward slanting palpebral fissures (the opening between the upper and lower lids) and epicanthal folds (folds of skin between the upper eyelid and the nose) are clinical signs at birth suggesting the diagnosis of Down syndrome[57][58] especially in the Western World.

[citation needed] Visually significant congenital cataracts (clouding of the lens of the eye) occur more frequently with Down syndrome.

[59] 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.

[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.

[69] Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development, endothelial dysfunction, and proinflammatory genes.

[75] 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.

[76] 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.

[78] In trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to the development of TAM on the preleukemic pathway.

[73][79][78] 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.

[92] Down syndrome (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males)[99] is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development, known as nondisjunction.

[91] Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3,[106] with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene.

[29] None can be definitive; thus, if screening predicts a high possibility of Down syndrome, either amniocentesis or chorionic villus sampling is required to confirm the diagnosis.

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.

[117][118] The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high likelihood of trisomy 21.

[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.

[129] In the United States, the Individuals with Disabilities Education Act of 1975 requires public schools generally to allow attendance by students with Down syndrome.

[64] Efforts to prevent respiratory syncytial virus (RSV) infection with human monoclonal antibodies should be considered, especially in those with heart problems.

[145] 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.

[30] In June 2020, the earliest incidence of Down syndrome was found in genomic evidence from an infant that was buried before 3200 BC at Poulnabrone dolmen in Ireland.

[156] 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,[157] and the 16th-century painting The Adoration of the Christ Child.

[158][159] 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.

[185] 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.

[187] 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.

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.

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

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.