Down syndrome

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Down syndrome
Classification and external resources
Boy with Down syndrome assembling a bookcase
ICD-10 Q90
ICD-9 758.0
OMIM 190685
DiseasesDB 3898
MedlinePlus 000997
eMedicine ped/615
MeSH D004314




Down syndrome is the most common chromosome abnormality in humans,[3] occurring in about 1 per 1000 babies born each year.[2] It is named after John Langdon Down, the British doctor who fully described the syndrome in 1866.[11] Some aspects of the condition were described earlier by Jean-Étienne Dominique Esquirol in 1838 and Édouard Séguin in 1844.[12] The genetic cause of Down syndrome—an extra copy of chromosome 21—was identified by French researchers in 1959.[11]

Signs and symptoms

A drawing of the facial features of an infant with Down syndrome

Those with Down syndrome nearly always have physical and intellectual disabilities.[13] As adults their mental abilities are typically similar to that of an 8 or 9 year old.[3] They also typically have poor immune function[14] and generally reach developmental milestones at a later age.[10] They have an increased risk of a number of other health problems, including: congenital heart disease, leukemia, thyroid disorders, and mental illness, among others.[11]

Characteristics Percentage Characteristics Percentage
Mental impairment 99%[15] Abnormal teeth 60%[16]
Stunted growth 90%[17] Slanted eyes 60%[14]
Umbilical hernia 90%[18] Shortened hands 60%[16]
Increased skin back of neck 80%[11] Short neck 60%[16]
Low muscle tone 80%[19] Obstructive sleep apnea 60%[11]
Narrow roof of mouth 76%[16] Bent fifth finger tip 57%[14]
Flat head 75%[14] Brushfield spots in the iris 56%[14]
Flexible ligaments 75%[14] Single transverse palmar crease 53%[14]
Large tongue 75%[19] Protruding tongue 47%[16]
Abnormal outer ears 70%[11] Congenital heart disease 40%[16]
Flattened nose 68%[14] Strabismus ~35%[2]
Separation of 1st and 2nd toes 68%[16] Undescended testicles 20%[20]


Feet of a boy with Down syndrome

People with Down syndrome may have some or all of the following physical characteristics: a small chin, slanted eyes, poor muscle tone, a flat nasal bridge, a single crease of the palm, and a protruding tongue due to a small mouth and large tongue.[19] These airway changes lead to obstructive sleep apnea in around half of those with Down syndrome.[11] Other common features include: a flat and wide face,[19] a short neck, excessive joint flexibility, extra space between big toe and second toe, abnormal patterns on the fingertips and short fingers.[16][19] Instability of the atlanto-axial joint occurs in approximately 20% and may lead to spinal cord injury in 1–2%.[3][10] Hip dislocations may occur without trauma in up to a third of people with Down syndrome.[11]

Growth in height is slower resulting in adults who tend to have short stature—the average height for men is 154 cm (5 feet 1 inch) and for women is 142 cm (4 feet 8 inches).[21] Individuals with Down syndrome are at increased risk for obesity as they age.[11] There are growth charts specifically for children with Down syndrome.[11]


Most individuals with Down syndrome have mild (IQ: 50–70) or moderate (IQ: 35–50) intellectual disability with some cases having severe (IQ: 20–35) difficulties.[2][22] Those with mosaic Down syndrome typically have IQ scores 10–30 points higher.[23] As they age people with Down syndrome typically perform less well compared to their same-age peers.[22][24] Some after 30 years of age may lose their ability to speak.[3] This syndrome causes about a third of cases of intellectual disability.[14] Many developmental milestones are delayed with the ability to crawl typically occurring around 8 months rather than 5 months and the ability to walk independently typically occurring around 21 months rather than 14 months.[25]

Commonly individuals with Down syndrome have better language understanding than ability to speak.[11][22] Between 10 and 45 percent have either a stutter or rapid and irregular speech, making it difficult to understand them.[26] They typically do fairly well with social skills.[11] Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability.[22] 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.[27] While generally happy,[28] symptoms of depression and anxiety may develop in early adulthood.[3]

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.[3] This includes an increased risk of a specific type of seizure called infantile spasms.[11] Many (15%) who live 40 years or longer develop dementia of the Alzheimer's type.[29] In those who reach 60 years of age, 50–70% have the disease.[3]




Hearing problems are found in 50–90% of children with Down syndrome.[30] This is often the result of otitis media with effusion which occurs in 50–70%[10] and chronic ear infections which occur in 40 to 60%.[31] Ear infections often begin in the first year of life and are partly due to poor eustachian tube function.[32][33] Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal.[3] Even a mild degree of hearing loss can have negative consequences for speech, language understanding and academics.[2][33] Additionally, it is important to rule out hearing loss as a factor in social and cognitive deterioration.[34] Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome.[3]


The rate of congenital heart disease in newborns with Down syndrome is around 40%.[16] Of those with heart disease, about 80% have an atrioventricular septal defect or ventricular septal defect.[3] Mitral valve problems become common as people age, even in those without heart problems at birth.[3] Other problems that may occur include tetralogy of Fallot and patent ductus arteriosus.[32] People with Down syndrome have a lower risk of hardening of the arteries.[3]


Although the overall risk of cancer is not changed;[35] there is an increased risk of leukemia and testicular cancer and a reduced risk of solid cancers.[3] Solid cancers are believed to be less common due to increased expression of tumor suppressor genes present on chromosome 21.[36]

Cancers of the blood are 10 to 15 times more common in children with Down syndrome.[11] In particular, acute lymphoblastic leukemia is 20 times more common and the megakaryoblastic form of acute myelogenous leukemia is 500 times more common.[37] Transient myeloproliferative disease, a disorder of blood cell production that does not occur outside of Down syndrome, affects 3–10% of infants.[37][38] The disorder is typically not serious but occasionally can be.[38] It resolves most times without treatment; however, in those who have had it there is a 20 to 30 percent risk of developing acute lymphoblastic leukemia at a later time.[38]


Problems of the thyroid gland occur in 20–50% of individuals with Down syndrome.[3][11] Low thyroid is the most common form, occurring in almost half of all individuals.[3] Thyroid problems can be due to a poorly or non functioning 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.[39] Type 1 diabetes mellitus is also more common.[3]


Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior.[11] One potential cause is Hirschsprung's disease, occurring in 2–15%, which is due to a lack of nerve cells controlling the colon.[40] Other frequent congenital problems include duodenal atresia, pyloric stenosis, Meckel diverticulum and imperforate anus.[32] Celiac disease affects about 7–20%[3][11] and gastroesophageal reflux disease is also more common.[32]


Males with Down syndrome usually do not father children, while females have lower rates of fertility relative those who are unaffected.[41] Fertility is estimated to be present in 30–50% of women.[42] Menopause typically occurs at an earlier age.[3] The poor fertility in men is thought to be due to problems with sperm development; however, it may also be related to not being sexually active.[41] As of 2006 there have been three recorded instances of males with Down syndrome fathering children and 26 cases of women having children.[41] Without assisted reproductive technologies, approximately half of the pregnancies of someone with Down syndrome will also have the syndrome.[41][43]


Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two.[1][44] The parents of the affected individual are typically genetically normal.[14] Those who have one child with Down syndrome have about a 1% risk of having a second child with the syndrome, if both parents are found to have normal karyotypes.[42]

The extra chromosome content can arise through several different ways. The most common cause (approximately 92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21.[43][45] In 1 to 2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down syndrome.[42][46] 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 approximately 2.5% of cases.[11][42] 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.[43]

Trisomy 21


Trisomy 21 (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males)[47] is caused by a failure of the 21st chromosome to separate during egg or sperm development.[43] 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 embryo and baby has 47 chromosomes, with three copies of chromosome 21.[1][43] About 88% of cases of trisomy 21 result from non separation of the chromosomes in the mother, 8% from non-separation in the father, and 3% after the egg and sperm have merged.[48]


The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% cases.[42][49] In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14.[50] In a male affected with Down syndrome it results in a karyotype of 46XY,t(14q21q).[50][51] This may be a new mutation or previously present in one of the parents.[52] The parent with such a translocation is usually normal physically and mentally;[50] however, during production of egg or sperm cells there is a higher chance of creating reproductive cells with extra chromosome 21 material.[49] This results in a 15% chance of having a child with Down syndrome when the mother is affected and a less than 5% risk if the father is affected.[52] The risk of this type of Down syndrome is not related to the mother's age.[50] Some children without Down syndrome may inherit the translocation and have a higher risk of having children of their own with Down syndrome.[50] In this case it is sometimes known as familial Down syndrome.[53]


The extra genetic material present in DS results in over-expression of a portion of the 310 genes located on chromosome 21.[44] This over-expression has been estimated at around 50%.[42] Some research has suggested that the Down syndrome critical region is located at bands 21q22.1–q22.3,[54] with this area including genes for amyloid, superoxide dismutase, and likely the ETS-2 proto oncogene.[55] Other research, however, has not confirmed these findings.[44]

The dementia which occurs in Down syndrome is due to an excess of amyloid beta peptide produced in the brain and is similar to Alzheimer's disease.[56] This peptide is processed from amyloid precursor protein whose gene is located on chromosome 21.[56] Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age even though dementia may not be present.[14] Those with DS also lack a normal number of lymphocytes and produce less antibodies which contributes to their increased risk of infection.[11]


Guidelines recommend that screening for Down syndrome be offered to all pregnant women, regardless of age.[57][58] A number of tests can be used, with varying levels of accuracy. They are usually used in combination to increase the detection rate, while maintaining a low false positive rate.[11] None can be definitive, thus if screening is positive either amniocentesis or chorionic villous sampling is required to confirm the diagnosis.[57] Screening in both the first and second trimesters is better than just screening in the first trimester.[57] The different screening techniques in use are able to pick up 90 to 95% of cases with a false positive rate of between 2 and 5%.[59]

First and second trimester screening[57]
Screen Week of pregnancy when performed Detection rate False positive Description
Cell-free fetal DNA From 10 wks[60] 96-100%[61] 0.3%[62] A blood sample is taken from the mother by venipuncture and is sent for DNA analysis.


Ultrasound of fetus with Down syndrome showing a large bladder

Ultrasound imaging can be used to screen for Down syndrome. Findings that indicate increased risk 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.[63] The presence or absence of many markers is more accurate.[63] Increased fetal nuchal translucency (NT) indicates an increased risk of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.[64]

Blood tests

Several blood markers can be measured to predict the risk of Down syndrome during the first or second trimester.[59][65] Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results.[59] 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.[65]

Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester.[66][67] The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high risk for trisomy 21.[68] Accuracy has been reported at 98.6% in the first trimester of pregnancy.[11] Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.[68]


Before birth

When screening tests predict a high risk of Down syndrome, a more invasive diagnostic test (amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis.[57] If Down syndrome occurs in 1 in 500 pregnancies and the test used has a 5% false positive rate, this means that of 28 women who test positive on screening only 1 will have Down syndrome confirmed.[59] If the screening test has a 2% false positive rate this means that 1 out of 10 who test positive on screening having a fetus with DS.[59] Amniocentesis and chorionic villus sampling are more reliable; however, they carry an increased risk of miscarriage of between 0.5 and 1%.[69] There is also an increased risk of limb problems in the offspring due to the procedure.[69] The risk from the procedure is greater the earlier it is performed and thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.[69]

Abortion rates

About 92% of pregnancies in the United Kingdom and Europe with a diagnosis of Down syndrome are terminated.[5] In the United States termination rates are around 67%; however this varies significantly depending upon the population looked at.[4] When non pregnant people are 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 screen positive are asked 89–97% say yes.[70]

After birth

The diagnosis can often be suspected based on the child's physical appearance at birth.[10] An analysis of the child's chromosomes is needed to confirm the diagnosis and determine if a translocation is present as this may help determine the risk of the child's parents having further children with Down syndrome.[10] Parents generally wish to know the possible diagnosis once it is suspected and do not wish pity.[11]


Efforts such as early childhood intervention, screening for common problems, medical treatment where indicated, a good family environment, and work related training can improve the development of children with Down syndrome. Education and proper care can improve quality of life.[6] Raising a child with Down syndrome is more work for parents than raising a non effected child.[71] Typical childhood vaccinations are recommended.[11]

Health screening

Recommended screening
Testing Children[72] Adults[3]
T4 and TSH 6 months, then yearly
Eyes 6 months, then yearly 3–5 years
Teeth 2 years, then every 6 months.
Coeliac 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.[72] It is recommended that this be done systematically.[11]

At birth all children should get an electrocardiogram and ultrasound of the heart.[11] Surgical repair of heart problems may be required as early as three months of age.[11] Heart valve problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood.[11] Due to the elevated risk of testicular cancer, some recommend checking the person's testicles yearly.[3]

Cognitive development

Hearing aids or other amplification devices can be useful for language learning in those with hearing loss.[11] Speech therapy may be useful and it is recommended that it be started around 9 months of age.[11] As those with Down's typically have good hand eye coordination, learning sign language may be possible.[22] Augmentative and alternative communication methods, such as pointing, body language, objects, or pictures are often used to help with communication even though there is little concrete evidence.[73] Behavioral issues and mental illness are typically managed with counseling and/or medications.[10]

Education programs before reaching school age may be useful.[2] 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 that some adjustments are made to the curriculum.[74] Evidence to support this however is not very strong.[75] In the United States the Individuals with Disabilities Education Act of 1975 requires that public schools generally allow attendance by students with Down's.[76]


Tympanostomy tubes are often needed[11] and often more than one set during the person's childhood.[30] Tonsillectomy is also often done to help with sleep apnea and throat infections.[11] Surgery, however, does not always address the sleep apnea and a continuous positive airway pressure (CPAP) machine may be useful.[30] Physical therapy and participation in physical education may improve motor skills.[77] Evidence to support this in adults, however, is not very good.[78]






Individuals with Down syndrome have a higher risk of early death than the general population.[11] This is most often from heart problems or infections.[2][3] Following improved medical care, particularly for heart and gastrointestinal problems, the life expectancy has increased.[2] This increase has been from 12 years in 1912,[88] to 25 years in the 1980s,[2] to 50 to 60 years in the developed world in the 2000s.[3][10] Currently between 4 and 12% die in the first year of life.[38] The probability of long-term survival is partly determined by the presence of heart problems. In those with congenital heart problems 60% survive to 10 years and 50% survive to 30 years of age.[14] In those without heart problems 85% survive to 10 years and 80% survive to 30 years of age.[14] About 10% live to 70 years of age.[43]



Globally, as of 2010, Down syndrome occurs in about 1 per 1000 births[2] and results in about 17,000 deaths.[90] It occurs more commonly in countries where abortion is not allowed and in countries where pregnancy more commonly occurs at a later age.[2] About 1.4 per 1000 live births in the United States[91] and 1.1 per 1000 live births in Norway are affected.[3] In the 1950s, in the United States, it occurred in 2 per 1000 live births with the decrease since then due to prenatal screening and abortions.[52] 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.[2]

Maternal age affects the chances of having a pregnancy with Down syndrome.[89] At age 20 the chance is 1 in 1441; 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.[89] Although the probability increases with maternal age, 70% of children with Down syndrome are born to women 35 years of age and younger, reflecting the fact that younger people have more children.[89] 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.[92]



English physician John Langdon Down first characterized Down syndrome as a separate form of mental disability in 1862, and in a more widely published report in 1866.[11][94][95] Édouard Séguin described it as separate from cretinism in 1944.[12][96] By the 20th century, Down syndrome had become the most recognizable form of mental disability.

In Ancient times many infants with disabilities were either killed or abandoned.[12] A number of historical pieces of art are believed to portray Down syndrome including pottery from AD 500 from South America and the 16th century painting "The Adoration of the Christ Child".[12]



Society and culture


Due to his perception that children with Down syndrome shared facial similarities with those of Blumenbach's Mongolian race, Down used the term mongoloid.[43][102] While the term "mongoloid" (also "mongolism" or "mongolian imbecility") continued to be used until the early 1970s, it is now considered unacceptable and is no longer in common use.[103] In 1961, 19 scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term".[103][104] The World Health Organization (WHO) dropped the term in 1965 after a request by the Mongolian delegate.[103]

In 1975, the United States National Institutes of Health (NIH) convened a conference to standardize the naming and recommended eliminating the possessive form,[105] although both the possessive and non-possessive forms are used by the general population.[106] The term "trisomy 21" is also used frequently.[104][107]




Within Christianity, Protestants often see abortion as acceptable when a fetus has Down syndrome,[116] while Orthodox Christians and Roman Catholics often do not.[116] Some of those against screening refer to it as a form of "eugenics".[116] There is disagreement within Islam regarding the acceptability of abortion in those who have a pregnancy with Down syndrome.[117] Some Islamic countries allow abortion while others do not.[117] Women may face stigmatization whichever decision they make.[118]

Advocacy groups

Advocacy groups for Down syndrome formed after the Second World War.[119] 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,[119] as well as groups providing support for families with children with Down syndrome.[119] Organizations included the Royal Society for Handicapped Children and Adults (MENCAP) founded in the UK in 1946 by Judy Fryd,[119][120] Kobato Kai founded in Japan in 1964,[119] the National Down Syndrome Congress founded in the United States in 1973 by Kathryn McGee and others,[119][121] and the National Down Syndrome Society founded in 1979 in the United States.[119]



There are efforts to determine how the extra chromosome 21 material causes Down syndrome as currently this is unknown.[124] There are also efforts to develop treatments to improve intelligence in those with Down's.[125] One hope is to use stem cells.[124] Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonist, and memantine.[126] Research is often carried out on an animal model, the Ts65Dn mouse.[127]


  1. ^ a b c Patterson, D (Jul 2009). "Molecular genetic analysis of Down syndrome.". Human genetics 126 (1): 195–214. doi:10.1007/s00439-009-0696-8. PMID 19526251. 
  10. ^ a b c d e f g h i j k l m n "Down Syndrome and Other Abnormalities of Chromosome Number". Nelson textbook of pediatrics. (19th ed. ed.). Philadelphia: Saunders. 2011. pp. Chapter 76.2. ISBN 1-4377-0755-6. 
  13. ^ Faragher, edited by Rhonda; Clarke, Barbara (2013). Educating Learners with Down Syndrome Research, theory, and practice with children and adolescents.. Hoboken: Taylor and Francis. p. 5. ISBN 978-1-134-67335-3. 
  46. ^ Kausik Mandal (2013). Treatment & prognosis in pediatrics.. Jaypee Brothers Medical P. p. 391. ISBN 978-93-5090-428-2. 
  52. ^ a b c Menkes, John H.; Sarnat, Harvey B. (2005). Child neurology (7th ed. ed.). Philadelphia, PA: Lippincott Williams & Wilkins. p. 228. ISBN 978-0-7817-5104-9. 
  54. ^ "Genetics of Down Syndrome". Retrieved 2011-05-29. 
  71. ^ Sheets KB, Crissman BG, Feist CD, et al. (October 2011). "Practice guidelines for communicating a prenatal or postnatal diagnosis of Down syndrome: recommendations of the national society of genetic counselors". J Genet Couns 20 (5): 432–41. doi:10.1007/s10897-011-9375-8. PMID 21618060. 
  78. ^ Andriolo, RB; El Dib, RP; Ramos, L; Atallah, AN; da Silva, EM (May 12, 2010). "Aerobic exercise training programmes for improving physical and psychosocial health in adults with Down syndrome.". The Cochrane database of systematic reviews (5): CD005176. PMID 20464738. 
  106. ^ Smith, Kieron (2011). The politics of down syndrome. [New Alresford, Hampshire]: Zero. p. 3. ISBN 978-1-84694-613-4. 
  107. ^ Westman, Judith A. (2005). Medical genetics for the modern clinician.. Philadelphia, PA: Lippincott Williams & Wilkins. p. 136. ISBN 978-0-7817-5760-7. 
  116. ^ a b c Bill J Leonard, Jill Y. Crainshaw (2013). Encyclopedia of religious controversies in the United States. (2nd ed. ed.). Santa Barbara, Calif.: ABC-CLIO. p. 278. ISBN 978-1-59884-867-0. 
  126. ^ Costa, AC; Scott-McKean, JJ (Sep 2013). "Prospects for improving brain function in individuals with Down syndrome.". CNS drugs 27 (9): 679–702. doi:10.1007/s40263-013-0089-3. PMID 23821040. 
  127. ^ Costa, AC (2011). "On the promise of pharmacotherapies targeted at cognitive and neurodegenerative components of Down syndrome.". Developmental neuroscience 33 (5): 414–27. doi:10.1159/000330861. PMID 21893967. 

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