Down's Syndrome, Down Syndrome
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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. It is usually associated with physical growth delays, mild to moderate intellectual disability, and characteristic facial features. The average IQ of a young adult with Down syndrome is 50, equivalent to the mental ability of an eight- or nine-year-old child, but this can vary widely. The parents of the affected individual are usually genetically normal. The probability increases from less than 0.1% in 20-year-old mothers to 3% in those of age 45. The extra chromosome is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability. Down syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing or after birth by direct observation and
genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
. Since the introduction of screening, Down syndrome
pregnancies Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but can ...
are often aborted. There is no cure for Down syndrome. Education and proper care have been shown to improve quality of life. Some children with Down syndrome are educated in typical school classes, while others require more specialized education. Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education. In adulthood, about 20% in the United States do paid work in some capacity, with many requiring a sheltered work environment. Support in financial and legal matters is often needed. Life expectancy is around 50 to 60 years in the developed world with proper health care. Regular
screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...
for health problems common in Down syndrome is recommended throughout the person's life. Down syndrome is one of the most common chromosome abnormalities in humans. It occurs in about 1 in 1,000 babies born each year. 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. It is named after British doctor
John Langdon Down John Langdon Haydon Down (18 November 1828 – 7 October 1896) was a British physician best known for his description of the genetic condition now known as Down syndrome, which he originally classified in 1862. He is also noted for his work in ...
, who fully described the syndrome in 1866. Some aspects of the condition were described earlier by French psychiatrist
Jean-Étienne Dominique Esquirol Jean-Étienne Dominique Esquirol (3 February 1772 – 12 December 1840) was a French psychiatrist. Early life and education Born and raised in Toulouse, Esquirol completed his education at Montpellier. He came to Paris in 1799 where he worked a ...
in 1838 and French physician Édouard Séguin in 1844. The genetic cause of Down syndrome was discovered in 1959.


Signs and symptoms

Those with Down syndrome nearly always have physical and intellectual disabilities. As adults, their mental abilities are typically similar to those of an 8- or 9-year-old. They also typically have
poor immune function Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
and generally reach
developmental milestones Child development stages are the theoretical milestones of child development, some of which are asserted in nativist theories. This article discusses the most widely accepted developmental stages in children. There exists a wide variation i ...
at a later age. They have an increased risk of a number of other health problems, including congenital heart defect, epilepsy, leukemia, thyroid diseases, and mental disorders.


Physical

People with Down syndrome may have some or all of these physical characteristics: a small chin, slanted eyes,
poor muscle tone Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...
, a flat nasal bridge, a single crease of the palm, and a protruding tongue due to a small mouth and relatively large tongue. These airway changes lead to
obstructive sleep apnea Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episod ...
in around half of those with Down syndrome. Other common features include: a flat and wide face, a short neck, excessive joint flexibility, extra space between big toe and second toe, abnormal patterns on the fingertips and short fingers. Instability of the
atlantoaxial joint The atlanto-axial joint is a joint in the upper part of the neck between the atlas bone and the axis bone, which are the first and second cervical vertebrae. It is a pivot joint. Structure The atlanto-axial joint is a joint between the atlas ...
occurs in about 20% and may lead to spinal cord injury in 1–2%.
Hip dislocation A hip dislocation is when the thighbone (femur) separates from the hip bone (pelvis). Specifically it is when the ball–shaped head of the femur (femoral head) separates from its cup–shaped socket in the hip bone, known as the acetabulum. Th ...
s may occur without trauma in up to a third of people with Down syndrome. 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). Individuals with Down syndrome are at increased risk for obesity as they age.
Growth chart A growth chart is used by pediatricians and other health care providers to follow a child's growth over time. Growth charts have been constructed by observing the growth of large numbers of healthy children over time. The height, weight, and head ...
s have been developed specifically for children with Down syndrome.


Neurological

This syndrome causes about a third of cases of intellectual disability. 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. 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, people with Down syndrome typically perform worse than their same-age peers. Commonly, individuals with Down syndrome have better language understanding than ability to speak. Between 10 and 45% have either a
stutter Stuttering, also known as stammering, is a speech disorder in which the flow of speech is disrupted by involuntary repetitions and prolongations of sounds, syllables, words, or phrases as well as involuntary silent pauses or blocks in which the ...
or rapid and irregular speech, making it difficult to understand them. After reaching 30 years of age, some may lose their ability to speak. They typically do fairly well with social skills. Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability. In children with Down syndrome,
mental illness A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
occurs in nearly 30% with
autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
occurring in 5–10%. People with Down syndrome experience a wide range of emotions. While people with Down syndrome are generally happy, symptoms of depression and anxiety may develop in early adulthood. 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. This includes an increased risk of a specific type of seizure called
infantile spasms Epileptic spasms is an uncommon-to-rare epileptic disorder in infants, children and adults. One of the other names of the disorder, West syndrome, is in memory of the English physician, William James West (1793–1848), who first described it in ...
. Many (15%) who live 40 years or longer develop
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. In those who reach 60 years of age, 50–70% have the disease.


Senses

Hearing and vision disorders occur in more than half of people with Down syndrome. Vision problems occur in 38 to 80%. Between 20 and 50% have strabismus, in which the two eyes do not move together. Cataracts (cloudiness of the lens of the eye) occur in 15%, and may be present at birth.
Keratoconus Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usu ...
(a thin, cone-shaped cornea) and glaucoma (increased eye pressure) are also more common, as are refractive errors requiring glasses or contacts.
Brushfield spots Brushfield spots are small, white or greyish/brown spots on the periphery of the iris in the human eye due to aggregation of connective tissue, a normal constituent of the iris stroma. The spots are named after the physician Thomas Brushfield, ...
(small white or grayish/brown spots on the outer part of the iris) are present in 38 to 85% of individuals. Hearing problems are found in 50–90% of children with Down syndrome. This is often the result of otitis media with effusion which occurs in 50–70% and chronic
ear infections Otitis is a general term for inflammation or infection, inner ear infection, middle ear infection of the ear, in both humans and other animals. When infection is present, it may be viral or bacterial. When inflammation is present due to fluid bui ...
which occur in 40 to 60%. Ear infections often begin in the first year of life and are partly due to poor
eustachian tube In anatomy, the Eustachian tube, also known as the auditory tube or pharyngotympanic tube, is a tube that links the nasopharynx to the middle ear, of which it is also a part. In adult humans, the Eustachian tube is approximately long and in d ...
function. Excessive
ear wax An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists ...
can also cause hearing loss due to obstruction of the outer
ear canal The ear canal (external acoustic meatus, external auditory meatus, EAM) is a pathway running from the outer ear to the middle ear. The adult human ear canal extends from the pinna to the eardrum and is about in length and in diameter. Struc ...
. Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics. It is important to rule out hearing loss as a factor in social and cognitive deterioration. Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome.


Heart

The rate of congenital heart disease in newborns with Down syndrome is around 40%. Of those with heart disease, about 80% have an atrioventricular septal defect or ventricular septal defect with the former being more common. 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. Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development, endothelial dysfunction, and proinflammatory genes.
Mitral valve The mitral valve (), also known as the bicuspid valve or left atrioventricular valve, is one of the four heart valves. It has two cusps or flaps and lies between the left atrium and the left ventricle of the heart. The heart valves are all one-w ...
problems become common as people age, even in those without heart problems at birth. Other problems that may occur include tetralogy of Fallot and patent ductus arteriosus. People with Down syndrome have a lower risk of
hardening of the arteries Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no sy ...
.


Cancer

Although the overall risk of cancer in Down syndrome is not changed, the risk of testicular cancer and certain blood cancers, including
acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
(ALL) and acute megakaryoblastic leukemia (AMKL) is increased while the risk of other non-blood cancers is decreased. 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.


Blood cancers

Leukemia is 10 to 15 times more common in children with Down syndrome. In particular,
acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
is 20 times more common and the
megakaryoblastic A megakaryoblast is a precursor cell to a promegakaryocyte, which in turn becomes a megakaryocyte during haematopoiesis. It is the beginning of the thrombocytic series. Development The megakaryoblast derives from a CFU-Meg colony unit of pluripote ...
form of acute myeloid leukemia ( acute megakaryoblastic leukemia), is 500 times more common. Acute megakaryoblastic leukemia (AMKL) is a leukemia of
megakaryoblast A megakaryoblast is a precursor cell to a promegakaryocyte, which in turn becomes a megakaryocyte during haematopoiesis. It is the beginning of the thrombocytic series. Development The megakaryoblast derives from a CFU-Meg colony unit of pluripote ...
s, the precursors cells to megakaryocytes which form blood platelets. 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. 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. The condition affects 3–10% of babies with Down. While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications. 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. This low risk is thought due to an increase in the expression of tumor suppressor genes present on chromosome 21. One exception is testicular
germ cell cancer Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embry ...
which occurs at a higher rate in Down syndrome.


Endocrine

Problems of the
thyroid gland The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobe (anatomy), lobes. The lower two thirds of the lobes are connected by a thin band of Connective tissue, tissue cal ...
occur in 20–50% of individuals with Down syndrome. Low thyroid is the most common form, occurring in almost half of all individuals. Thyroid problems can be due to a poorly or nonfunctioning thyroid at birth (known as congenital hypothyroidism) which occurs in 1% or can develop later due to an attack on the thyroid by the immune system resulting in
Graves' disease Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyr ...
or
autoimmune hypothyroidism Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it. It may ...
. Type 1 diabetes mellitus is also more common.


Gastrointestinal

Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior. One potential cause is Hirschsprung's disease, occurring in 2–15%, which is due to a lack of nerve cells controlling the colon. Other frequent congenital problems include
duodenal atresia Duodenal atresia is the congenital absence or complete closure of a portion of the lumen of the duodenum. It causes increased levels of amniotic fluid during pregnancy ( polyhydramnios) and intestinal obstruction in newborn babies. Newborns pres ...
, pyloric stenosis,
Meckel diverticulum A Meckel's diverticulum, a true congenital diverticulum, is a slight bulge in the small intestine present at birth and a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct or yolk stalk). It is the most common malforma ...
, and
imperforate anus An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unknow ...
. Celiac disease affects about 7–20% and gastroesophageal reflux disease is also more common.


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. While plaque and poor oral hygiene are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors. Research suggests that the severity is likely a result of a weakened immune system. The weakened immune system also contributes to increased incidence of
yeast infections Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...
in the mouth (from '' Candida albicans''). People with Down syndrome also tend to have a more
alkaline In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a base (chemistry), basic, ionic compound, ionic salt (chemistry), salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as ...
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
resulting in a greater resistance to tooth decay, despite decreased quantities of saliva, less effective oral hygiene habits, and higher plaque indexes. Higher rates of tooth wear and
bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; reports of prevalence range from 8% to 31% in the gene ...
are also common. 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 Deciduous teeth or primary teeth, also informally known as baby teeth, milk teeth, or temporary teeth,Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 255 are the first set of teeth in the ...
and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth. Less common manifestations include cleft lip and palate and enamel hypocalcification (20% prevalence).
Taurodontism Taurodontism is defined as the enlargement of pulp chambers with the furcation area being displaced toward the apex of the root. It cannot be diagnosed clinically and requires radiographic visualization since the crown of a taurodontic tooth ap ...
, an elongation of the pulp chamber, has a high prevalence in people with DS.


Fertility

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


Cause

The cause of the extra full or partial chromosome is still unknown. Most of the time, Down syndrome is caused by a random mistake in cell division during early development of the fetus, but not inherited, and no scientific research 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 maternal age. 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. 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
karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
s. 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. In 1.0 to 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 Robertsonian translocation (ROB) is a chromosomal abnormality wherein a certain type of a chromosome becomes attached to another. It is the most common form of chromosomal translocation in humans, affecting 1 out of every 1,000 babies born. It doe ...
,
isochromosome An isochromosome is an unbalanced structural abnormality in which the arms of the chromosome are mirror images of each other. The chromosome consists of two copies of either the long (q) arm or the short (p) arm because isochromosome formation ...
, or ring chromosome. These contain additional material from chromosome 21 and occur in about 2.5% of cases. 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.


Trisomy 21

Trisomy 21 (also known by the
karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
47,XX,+21 for females and 47,XY,+21 for males) is caused by a failure of the 21st chromosome to separate during egg or sperm development ( nondisjunction). 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. 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.


Mosaicism

Mosaicism 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. Mosaicism is the least common form of Down syndrome and accounts for only about 1% of all cases of Down syndrome. 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.


Translocation

The extra chromosome 21 material may also occur due to a
Robertsonian translocation Robertsonian translocation (ROB) is a chromosomal abnormality wherein a certain type of a chromosome becomes attached to another. It is the most common form of chromosomal translocation in humans, affecting 1 out of every 1,000 babies born. It doe ...
in 2–4% of cases. In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14. In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q). This may be a new mutation or previously present in one of the parents. The parent with such a translocation is usually normal physically and mentally; however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists. 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. The probability of this type of Down syndrome is not related to the mother's age. Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome. In this case it is sometimes known as familial Down syndrome.


Mechanism

The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21. This overexpression has been estimated at 50%, due to the third copy of the chromosome present. Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, with this area including genes for the
amyloid precursor protein Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator ...
,
superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen me ...
, and likely the
ETS2 Protein C-ETS2 is a protein that in humans is encoded by the ''ETS2'' gene. The protein encoded by this gene belongs to the ETS family of transcription factors. Interactions ETS2 has been shown to interact with: * C-jun, * Cyclin-depende ...
proto oncogene. Other research, however, has not confirmed these findings. MicroRNAs are also proposed to be involved. The dementia that occurs in Down syndrome is due to an excess of
amyloid beta Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
peptide produced in the brain and is similar to
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, which also involves amyloid beta build-up. Amyloid beta is processed from
amyloid precursor protein Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator ...
, the gene for which is located on chromosome 21. Senile plaques and
neurofibrillary tangle Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is kn ...
s are present in nearly all by 35 years of age, though dementia may not be present. Those with Down syndrome also lack a normal number of
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
and produce less
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
which contributes to their increased risk of infection.


Epigenetics

Down syndrome is associated with an increased risk of many chronic diseases that are typically associated with older age such as Alzheimer's disease. The accelerated aging suggest that trisomy 21 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 An epigenetic clock is a biochemical test that can be used to measure age. The test is based on DNA methylation levels, measuring the accumulation of methyl groups to one's DNA molecules. History The strong effects of age on DNA methylation le ...
, trisomy 21 increases the age of blood and brain tissue (on average by 6.6 years).


Diagnosis


Before birth

When screening tests predict a high possibility of Down syndrome, a more invasive diagnostic test ( amniocentesis or
chorionic villus sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It ent ...
) is needed to confirm the diagnosis. The false-positive rate with screening is about 2–5% (see section
Screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...
below). Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
by between 0.5 and 1%. 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.


Abortion rates

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


After birth

The 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 Translocation may refer to: * Chromosomal translocation, a chromosome abnormality caused by rearrangement of parts ** Robertsonian translocation, a chromosomal rearrangement in pairs 13, 14, 15, 21, and 22 ** Nonreciprocal translocation, transfer ...
is present, as this may help determine the chances of the child's parents having further children with Down syndrome. Parents generally wish to know the possible diagnosis once it is suspected and do not


Screening

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. None can be definitive, thus if screening is positive, either amniocentesis or
chorionic villus sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It ent ...
is required to confirm the diagnosis. Screening in both the first and second trimesters is better than just screening in the first trimester. The different screening techniques in use are able to pick up 90–95% of cases, with a false-positive rate of 2–5%. 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. If the screening test has a 2% false-positive rate, this means, of 50 women who test positive on screening, one will have a fetus with Down syndrome.


Ultrasound

Ultrasound imaging can be used to screen for Down syndrome. Findings that indicate increased chances when seen at 14 to 24 weeks of
gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...
include a small or no nasal bone, large ventricles,
nuchal fold thickness A nuchal scan or nuchal translucency (NT) scan/procedure is a sonographic prenatal screening scan (ultrasound) to detect chromosomal abnormalities in a fetus, though altered extracellular matrix composition and limited lymphatic drainage can also ...
, and an abnormal right
subclavian artery In human anatomy, the subclavian arteries are paired major arteries of the upper thorax, below the clavicle. They receive blood from the aortic arch. The left subclavian artery supplies blood to the left arm and the right subclavian artery supplie ...
, among others. The presence or absence of many markers is more accurate. Increased fetal
nuchal translucency A nuchal scan or nuchal translucency (NT) scan/procedure is a sonographic prenatal screening scan (ultrasound) to detect chromosomal abnormalities in a fetus, though altered extracellular matrix composition and limited lymphatic drainage can also ...
(NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%. 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 in both trimesters is sometimes recommended and test results are often combined with ultrasound results. In the second trimester, often two or three tests are used in combination with two or three of:
α-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
, unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases. 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. Accuracy has been reported at 98.6% in the first trimester of pregnancy. Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.


Management

Efforts such as
early childhood intervention Early childhood intervention (ECI) is a support and educational system for very young children (aged birth to six years) who have been victims of, or who are at high risk for child abuse and/or neglect as well as children who have developmental de ...
, 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. Raising a child with Down syndrome is more work for parents than raising an unaffected child. Typical childhood vaccinations are recommended.


Health screening

A number of health organizations have issued recommendations for
screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...
those with Down syndrome for particular diseases. This is recommended to be done systematically. At birth, all children should get an electrocardiogram and ultrasound of the heart. Surgical repair of heart problems may be required as early as three months of age. Heart valve problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood. Due to the elevated risk of testicular cancer, some recommend checking the person's testicles yearly.


Cognitive development

Hearing aids or other amplification devices can be useful for language learning in those with hearing loss.
Speech therapy Speech is a human vocal communication using language. Each language uses phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if they are th ...
may be useful and is recommended to be started around nine months of age. As those with Down syndrome typically have good hand-eye coordination, learning sign language may be possible. Augmentative and alternative communication methods, such as pointing, body language, objects, or pictures, are often used to help with communication. Behavioral issues and mental illness are typically managed with counseling or medications. Education programs before reaching school age may be useful. School-age children with Down syndrome may benefit from
inclusive education Inclusion in education refers to all students being able to access and gain equal opportunities to education and learning. It arose in the context of special education with an individualized education program or 504 plan, and is built on the ...
(whereby students of differing abilities are placed in classes with their peers of the same age), provided some adjustments are made to the curriculum. Evidence to support this, however, is not very strong. 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.


Other

Tympanostomy tubes are often needed and often more than one set during the person's childhood. Tonsillectomy is also often done to help with sleep apnea and throat infections. Surgery, however, does not always address the sleep apnea and a continuous positive airway pressure (CPAP) machine may be useful. Physical therapy and participation in physical education may improve motor skills. Evidence to support this in adults, however, is not very good. Efforts to prevent respiratory syncytial virus (RSV) infection with
human monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...
should be considered, especially in those with heart problems. In those who develop dementia there is no evidence for memantine, donepezil, rivastigmine, or galantamine. Plastic surgery has been suggested as a method of improving the appearance and thus the acceptance of people with Down syndrome. It has also been proposed as a way to improve speech. Evidence, however, does not support a meaningful difference in either of these outcomes. Plastic surgery on children with Down syndrome is uncommon, and continues to be controversial. The U.S.
National Down Syndrome Society The National Down Syndrome Society (NDSS) is an American organization that offers support to people with Down syndrome, their families, friends, teachers, and coworkers, and educates the general public about Down syndrome. The mission of the NDS ...
views the goal as one of mutual respect and acceptance, not appearance. Many alternative medical techniques are used in Down syndrome; however, they are poorly supported by evidence. These include: dietary changes, massage,
animal therapy Animal-assisted therapy (AAT) is an alternative or complementary type of therapy that includes the use of animals in a treatment. The goal of this animal-assisted intervention is to improve a patient's social, emotional, or cognitive functionin ...
, chiropractic and naturopathy, among others. Some proposed treatments may also be harmful.


Prognosis

Between 5 and 15% of children with Down syndrome in Sweden attend regular school. Some graduate from high school; however, most do not. Of those with intellectual disability in the United States who attended high school about 40% graduated. Many learn to read and write and some are able to do paid work. In adulthood about 20% in the United States do paid work in some capacity. In Sweden, however, less than 1% have regular jobs. Many are able to live semi-independently, but they often require help with financial, medical, and legal matters. Those with mosaic Down syndrome usually have better outcomes. Individuals with Down syndrome have a higher risk of early death than the general population. This is most often from heart problems or infections. Following improved medical care, particularly for heart and gastrointestinal problems, the life expectancy has increased. This increase has been from 12 years in 1912, to 25 years in the 1980s, to 50 to 60 years in the developed world in the 2000s. Currently between 4 and 12% die in the first year of life. 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. In those without heart problems, 85% survive to 10 years and 80% survive to 30 years of age. About 10% live to 70 years of age. The National Down Syndrome Society provide information regarding raising a child with Down syndrome.


Epidemiology

Down syndrome is the most common chromosomal abnormality in humans. Globally, , Down syndrome occurs in about 1 per 1,000 births and results in about 17,000 deaths. 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. About 1.4 per 1,000 live births in the United States and 1.1 per 1,000 live births in Norway are affected. 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. The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting. It is the cause of 8% of all congenital disorders.
Maternal age Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.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.


Life expectancy

According to the
Mayo Clinic The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staff, ...
, the average life expectancy of a person with Down syndrome is more than 60 years.


History

English physician
John Langdon Down John Langdon Haydon Down (18 November 1828 – 7 October 1896) was a British physician best known for his description of the genetic condition now known as Down syndrome, which he originally classified in 1862. He is also noted for his work in ...
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. In antiquity, many infants with disabilities were either killed or abandoned. 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. 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 Colombia (, ; ), officially the Republic of Colombia, is a country in South America with insular regions in North America—near Nicaragua's Caribbean coast—as well as in the Pacific Ocean. The Colombian mainland is bordered by the Car ...
and Ecuador, and the 16th-century painting ''The Adoration of the Christ Child''. 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 Eugenics ( ; ) is a fringe set of beliefs and practices that aim to improve the genetic quality of a human population. Historically, eugenicists have attempted to alter human gene pools by excluding people and groups judged to be inferior or ...
, 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 made public policy of a program of systematic involuntary euthanization. With the discovery of
karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape. In 1959
Jérôme Lejeune Jérôme Jean Louis Marie Lejeune (13 June 1926 – 3 April 1994) was a French pediatrician and geneticist, best known for discovering the link of diseases to chromosome abnormalities, most especially the link between Down Syndrome and trisomy- ...
reported the discovery that Down syndrome resulted from an extra chromosome. However, Lejeune's claim to the discovery has been disputed, and in 2014 the Scientific Council of the French Federation of Human Genetics unanimously awarded its Grand Prize to his colleague
Marthe Gautier Marthe Gautier (; 10 September 1925 – 30 April 2022) was a French medical doctor and researcher, best known for her role in discovering the link of diseases to chromosome abnormalities. Education Marthe Gautier discovered a vocation for ped ...
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. 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

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". He felt that the existence of Down syndrome confirmed 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". The World Health Organization (WHO) dropped the term in 1965 after a request by the delegation from the Mongolian People's Republic. While the term mongoloid (also mongolism, Mongolian imbecility or idiocy) continued to be used until the early 1980s, it is now considered unacceptable and is no longer in common use. 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". However, both the possessive and nonpossessive forms remain in use by the general population. The term "trisomy 21" is also commonly used.


Ethics

Most obstetricians argue that not offering screening for Down syndrome is unethical. As it is a medically reasonable procedure, per
informed consent Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
, people should at least be given information about it. It will then be the woman's choice, based on her personal beliefs, how much or how little screening she wishes. When results from testing become available, it is also considered unethical not to give the results to the person in question. 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 The disability rights movement is a global new social movements, social movement that seeks to secure equal opportunity, equal opportunities and equality before the law, equal rights for all people with disability, disabilities. It is made u ...
does not have a position on screening, although some members consider testing and abortion discriminatory. Some in the United States who are
anti-abortion Anti-abortion movements, also self-styled as pro-life or abolitionist movements, are involved in the abortion debate advocating against the practice of abortion and its legality. Many anti-abortion movements began as countermovements in respons ...
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. Within the US, some Protestant denominations see abortion as acceptable when a fetus has Down syndrome while Orthodox Christianity and
Roman Catholicism The Catholic Church, also known as the Roman Catholic Church, is the List of Christian denominations by number of members, largest Christian church, with 1.3 billion baptized Catholics Catholic Church by country, worldwide . It is am ...
do not. Some of those against screening refer to it as a form of eugenics. Disagreement exists within
Islam Islam (; ar, ۘالِإسلَام, , ) is an Abrahamic religions, Abrahamic Monotheism#Islam, monotheistic religion centred primarily around the Quran, a religious text considered by Muslims to be the direct word of God in Islam, God (or ...
regarding the acceptability of abortion in those carrying a fetus with Down syndrome. Some Islamic countries allow abortion, while others do not. Parents may be stigmatized whichever decision they make.


Advocacy groups

Advocacy groups for individuals with Down syndrome began to be formed after the Second World War. 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, as well as groups providing support for families with children living with Down syndrome. 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, Kobato Kai founded in Japan in 1964, the National Down Syndrome Congress founded in the United States in 1973 by
Kathryn McGee Kathryn "Kay" McGee (née Greene, May 6, 1920, in Chicago, Illinois – February 16, 2012 in River Forest, Illinois) was an American activist, recognized for founding two of the first organizations for the benefit of those with Down Syndrom ...
and others, and the
National Down Syndrome Society The National Down Syndrome Society (NDSS) is an American organization that offers support to people with Down syndrome, their families, friends, teachers, and coworkers, and educates the general public about Down syndrome. The mission of the NDS ...
founded in 1979 in the United States. The first Roman Catholic order of nuns for women with Down Syndrome,
Little Sisters Disciples of the Lamb The Little Sisters Disciples of the Lamb (french: Les Petites Soeurs Disciples de l'Agneau) is a Roman Catholic religious institute for women based in France. It is the world's first contemplative community to welcome those with Down syndrome int ...
, was founded in 1985 in France. The first
World Down Syndrome Day World Down Syndrome Day (WDSD) is marked each year on March 21, beginning in 2006. The 21st day of March (the 3rd month of the year) was selected to signify the uniqueness of the triplication (trisomy) of the 21st chromosome which causes Down synd ...
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.


Research

Efforts are underway to determine how the extra chromosome 21 material causes Down syndrome, as currently this is unknown, and to develop treatments to improve intelligence in those with the syndrome. Two efforts being studied are the use stem cells and gene therapy. Other methods being studied include the use of
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
s,
gamma secretase inhibition Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
,
adrenergic agonist An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between ...
s, and memantine. Research is often carried out on an animal model, the Ts65Dn mouse.


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 The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of Hominidae, great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close r ...
in 1969 and a
Bornean orangutan The Bornean orangutan (''Pongo pygmaeus'') is a species of orangutan endemic to the island of Borneo. Together with the Sumatran orangutan (''Pongo abelii'') and Tapanuli orangutan (''Pongo tapanuliensis''), it belongs to the only genus of great ...
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.


In popular culture

* ''Struck by Lightning'', an Australian film by
Jerzy Domaradzki Jerzy Domaradzki (born 6 January 1943, in Lwów, occupied Poland) is a Polish-born film director based in Australia. He is most closely associated with Poland's film industry. Following his 1974 graduation from the National Film School in ...
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.


References


External links

* Thompson, S.B.N. (2000). "The Central Executive System in people with Down's syndrome and dementia". Clinical Gerontologist. 21 (3): 3–32. Taylor & Francis (Routledge). DOI 10.1300/j018v21n03_02. eISSN 1545-2301. OCLC 1106716083. S2CID 218575706. * Thompson, S.B.N. (2000). "Investigation into Down's syndrome and dementia". ''Journal of the Association of Practitioners in Learning Disability, 17''(3): 10–14. * Thompson, S.B.N. (1999). "Examining dementia in Down's syndrome (DS): decline in social abilities in DS compared with other learning disabilities". ''Clinical Gerontologist, 20''(3): 23–44. Taylor & Francis (Routledge). DOI 10.1300/j018v20n03_04
eISSN An International Standard Serial Number (ISSN) is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is especially helpful in distinguishing between serials with the same title. ISSNs a ...
1545-2301
OCLC OCLC, Inc., doing business as OCLC, See also: is an American nonprofit cooperative organization "that provides shared technology services, original research, and community programs for its membership and the library community at large". It was ...
1106716083 *


External links

*
Down's syndrome
by the UK National Health Service {{Authority control Autosomal trisomies Chromosomal abnormalities Genetic diseases and disorders Genetic syndromes Intellectual disability Wikipedia medicine articles ready to translate (full) Syndromes affecting the gastrointestinal tract Syndromes affecting the heart Syndromes affecting the nervous system Syndromes with craniofacial abnormalities