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Down syndrome

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Down syndrome
   Classifications and external resources

   Child with Down syndrome using an electric drill
     ICD- 10   Q 90.
     ICD- 9    758.0
      OMIM     190685
   DiseasesDB  3898
   MedlinePlus 000997
    eMedicine  ped/615

   Down syndrome or trisomy 21 (also Down's syndrome) is a genetic
   disorder caused by the presence of all or part of an extra 21st
   chromosome. It is named after John Langdon Down, the British doctor who
   first described it in 1866. The condition is characterized by a
   combination of major and minor differences in body structure. Often
   Down syndrome is associated with some impairment of cognitive ability
   and physical growth as well as facial appearance. Down syndrome is
   usually identified at birth.

   Individuals with Down syndrome can have a lower than average cognitive
   ability, often ranging from mild to moderate mental retardation.
   Developmental disabilities often manifest as a tendency toward concrete
   thinking or naïveté. A small number suffer from severe to profound
   mental retardation. The incidence of Down syndrome is estimated at 1
   per 800 to 1 per 1,000 births.

   Many of the common physical features of Down syndrome also appear in
   people with a standard set of chromosomes. They include a single
   transverse palmar crease (a single instead of a double crease across
   one or both palms), an almond shape to the eyes caused by an epicanthic
   fold of the eyelid, shorter limbs, and protruding tongue. Health
   concerns for individuals with Down syndrome include a higher risk for
   congenital heart defects, gastroesophageal reflux disease, recurrent
   ear infections, obstructive sleep apnea, and thyroid dysfunctions.

   Early childhood intervention, screening for common problems, medical
   treatment where indicated, a conducive family environment, and
   vocational training can improve the overall development of children
   with Down syndrome. Although some of the physical genetic limitations
   of Down syndrome cannot be overcome, education and proper care will
   improve quality of life.

Characteristics

   Example of white spots on the iris known as Brushfield Spots
   Enlarge
   Example of white spots on the iris known as Brushfield Spots

   Individuals with Down syndrome may have some or all of the following
   physical characteristics: oblique eye fissures with epicanthic skin
   folds on the inner corner of the eyes, muscle hypotonia (poor muscle
   tone), a flat nasal bridge, a single palmar fold (also known as a
   simian crease), a protruding tongue (due to small oral cavity, and an
   enlarged tongue near the tonsils), a short neck, white spots on the
   iris known as Brushfield spots, excessive flexibility in joints,
   congenital heart defects, excessive space between large toe and second
   toe, and a single flexion furrow of the fifth finger. Most individuals
   with Down syndrome have mental retardation in the mild (IQ 50–70) to
   moderate (IQ 35–50) range, with scores of children having Mosaic Down
   syndrome (explained below) typically 10–30 points higher. In addition,
   individuals with Down syndrome can have serious abnormalities affecting
   any body system.

Genetics

   Karyotype for trisomy Down syndrome. Notice the three copies of
   chromosome 21.
   Enlarge
   Karyotype for trisomy Down syndrome. Notice the three copies of
   chromosome 21.

   Down syndrome is a chromosomal abnormality characterized by the
   presence of an extra copy of genetic material on the 21st chromosome,
   either in whole ( trisomy 21) or part (such as due to translocations).
   The effects of the extra copy vary greatly among individuals, depending
   on the extent of the extra copy, genetic background, environmental
   factors, and random chance. Down syndrome occurs in all human
   populations, and analogous effects have been found in other species
   such as chimpanzees and mice. Recently, researchers have created
   transgenic mice with most of human chromosome 21 (in addition to the
   normal mouse chromosomes). The extra chromosomal material can come
   about in several distinct ways. A normal human karyotype is designated
   as 46,XX or 46,XY, indicating 46 chromosomes with an XX arrangement for
   females and 46 chromosomes with an XY arrangement for males.

Trisomy 21

   Trisomy 21 (47,XX,+21) is caused by a meiotic nondisjunction event.
   With nondisjunction, a gamete (i.e., a sperm or egg cell) is produced
   with an extra copy of chromosome 21; the gamete thus has 24
   chromosomes. When combined with a normal gamete from the other parent,
   the embryo now has 47 chromosomes, with three copies of chromosome 21.
   Trisomy 21 is the cause of approximately 95% of observed Down
   syndromes, with 88% coming from nondisjunction in the maternal gamete
   and 8% coming from nondisjunction in the paternal gamete.

Mosaicism

   Trisomy 21 is generally caused prior to conception, and all cells in
   the body are affected. However, when some of the cells in the body are
   normal and other cells have trisomy 21, it is called Mosaic Down
   syndrome (46,XX/47,XX,+21). This can occur in one of two ways: A
   nondisjunction event during an early cell division in a normal embryo
   leads to a fraction of the cells with trisomy 21; or a Down syndrome
   embryo undergoes nondisjunction and some of the cells in the embryo
   revert back to the normal chromosomal arrangement. There is
   considerable variability in the fraction of trisomy 21, both as a whole
   and among tissues. This is the cause of 1–2% of the observed Down
   syndromes.

Robertsonian translocation

   The extra chromosome 21 material that causes Down syndrome may be due
   to a Robertsonian translocation. In this case, the long arm of
   chromosome 21 is attached to another chromosome, often chromosome 14
   (45,XX,t(14;21q)) or itself (called an isochromosome,
   45,XX,t(21q;21q)). Normal disjunctions leading to gametes have a
   significant chance of creating a gamete with an extra chromosome 21.
   Translocation Down syndrome is often referred to as familial Down
   syndrome. It is the cause of 2-3% of observed cases of Down syndrome.
   It does not show the maternal age effect, and is just as likely to have
   come from fathers as mothers.

Duplication of a portion of chromosome 21

   Rarely, a region of chromosome 21 will undergo a duplication event.
   This will lead to extra copies of some, but not all, of the genes on
   chromosome 21 (46,XX,dup(21q)). If the duplicated region has genes that
   are responsible for Down syndrome physical and mental characteristics,
   such individuals will show those characteristics. This cause is very
   rare and no rate estimates are available.

Incidence

   Graph showing increased chance of Down syndrome compared to maternal
   age.
   Enlarge
   Graph showing increased chance of Down syndrome compared to maternal
   age.

   The incidence of Down syndrome is estimated at 1 per 800 to 1 per 1000
   births. In 2006, the Centre for Disease Control estimated the rate as 1
   per 733 live births in the United States (5429 new cases per year).
   Approximately 95% of these are trisomy 21. Down syndrome occurs in all
   ethnic groups and among all economic classes.

   Maternal age influences the risk of conceiving a baby with Down
   syndrome. At maternal age 20 to 24, the risk is 1/1490; at age 40 the
   risk is 1/60, and at age 49 the risk is 1/11. Although the risk
   increases with maternal age, 80% of children with Down syndrome are
   born to women under the age of 35, reflecting the overall fertility of
   that age group. Other than maternal age, no other risk factors are
   known. There does not appear to be a paternal age effect.

   Many standard prenatal screens can discover Down syndrome. Genetic
   counseling along with genetic testing, such as amniocentesis, chorionic
   villus sampling (CVS), or percutaneous umbilical blood sampling (PUBS)
   are usually offered to families who may have an increased chance of
   having a child with Down syndrome, or where normal prenatal exams
   indicate possible problems. Genetic screens are often performed on
   pregnant women older than 30 or 35.

Prenatal screening

   Pregnant women can be screened for various complications in their
   pregnancy, or due to risk factors such as advanced maternal age. There
   are several common non-invasive screens that can indicate a fetus with
   Down syndrome, and are normally performed in the late first trimester
   or early second trimester. Due to the nature of screens, each has a
   significant chance of a false positive, suggesting a fetus with Down
   syndrome when, in fact, the fetus does not have this genetic
   abnormality. Screen positives must be verified before a Down syndrome
   diagnosis is made. Common screening procedures for Down syndrome are
   given in Table 1.

   CAPTION: Table 1: Common first and second trimester Down syndrome
   screens

   Screen When performed (weeks gestation) Detection rate False positive
   rate Description
   Triple screen 15–20 75% 8.5% This test measures the maternal serum
   alpha feto protein (a fetal liver protein), estriol (a pregnancy
   hormone), and human chorionic gonadotropin (hCG, a pregnancy hormone).
   Quad screen 15–20 79% 7.5% This test measures the maternal serum alpha
   feto protein (a fetal liver protein), estriol (a pregnancy hormone),
   human chorionic gonadotropin (hCG, a pregnancy hormone), and high
   inhibin-Alpha (INHA).
   AFP/free beta screen 13–22 80% 2.8% This test measures the alpha feto
   protein, produced by the fetus, and free beta hCG, produced by the
   placenta.
   Nuchal translucency/free beta/PAPPA screen 10–13.5 91% 5% Uses
   ultrasound to measure Nuchal Translucency in addition to the freeBeta
   hCG and PAPPA (pregnancy-associate plasma protein A, Mendelian
   Inheritance in Man (OMIM) 176385). NIH has confirmed that this first
   trimester test is more accurate than second trimester screening
   methods.
   Ultrasound of fetus with Down syndrome and megacystis
   Enlarge
   Ultrasound of fetus with Down syndrome and megacystis

   Even with the best non-invasive screens, the detection rate is 90%–95%
   and the rate of false positive is 2%–5%. False positives can be caused
   by undetected multiple fetuses (very rare with the ultrasound tests),
   incorrect date of pregnancy, or normal variation in the proteins.

   Confirmation of screen positive is normally accomplished with
   amniocentesis. This is an invasive procedure and involves taking
   amniotic fluid from the mother and identifying fetal cells. The lab
   work can take a couple of weeks but will detect over 99.8% of all
   numerical chromosomal problems with a very low false positive rate.

   Due to the low incidence of Down syndrome, a vast majority of early
   screen positives are false. Since the risk of spontaneous abortion is
   approximately 1/200 to 1/300, amniocentesis confirmation presents a
   risk of spontaneously aborting a healthy fetus (while testing from a
   false positive).

   A 2002 literature review of elective abortion rates found that 91–93%
   of pregnancies with a diagnosis of Down syndrome were terminated.
   Physicians and ethicists are concerned about the ethical ramifications,
   with some commentators calling it " eugenics by abortion". Many members
   of the disability rights movement "believe that public support for
   prenatal diagnosis and abortion based on disability contravenes the
   movement's basic philosophy and goals."

Cognitive development

   Cognitive development in children with Down syndrome is quite variable.
   It is not possible at birth to predict their capabilities. The
   identification of the best methods of teaching each particular child
   ideally begins soon after birth through early intervention programs.
   Since children with Down syndrome have a wide range of abilities,
   success at school can vary greatly, which stresses the importance of
   evaluating children individually. The cognitive problems that are found
   among children with Down syndrome can also be found among typical
   children. Therefore, parents can use general programs that are offered
   through the schools or other means.

   Language skills show a difference between understanding speech and
   expressing speech. It is common for children with Down syndrome to need
   speech therapy to help with expressive language. Fine motor skills are
   delayed and often lag behind gross motor skills and can interfere with
   cognitive development. Occupational therapy can address these issues.

   In education, mainstreaming of children with Down syndrome is
   controversial. Mainstreaming is the process whereby students of
   differing abilities are placed in classes with their chronological
   peers. Children with Down syndrome may not age emotionally/socially and
   intellectually at the same rates as children without Down syndrome, so
   over time the intellectual and emotional gap between children with and
   without Down syndrome may widen. Complex thinking as required in
   sciences but also in history, the arts, and other subjects can often be
   beyond some abilities, or achieved much later than in other children.
   Therefore, children with Down syndrome may benefit from mainstreaming
   provided that some adjustments are made to the curriculum.

   Some European countries such as Germany and Denmark advise a
   two-teacher system, whereby the second teacher takes over a group of
   children with disabilities within the class. A popular alternative is
   cooperation between special education schools and mainstream schools.
   In cooperation, the core subjects are taught in separate classes, which
   neither slows down the typical students nor neglects the students with
   disabilities. Social activities, outings, and many sports and arts
   activities are performed together, as are all breaks and meals.

Health

   The medical consequences of the extra genetic material in Down syndrome
   are highly variable and may affect the function of any organ system or
   bodily process. The health aspects of Down syndrome encompass
   anticipating and preventing effects of the condition, recognizing
   complications of the disorder, managing individual symptoms, and
   assisting the individual and his/her family in coping and thriving with
   any related disability or illnesses.

   The most common manifestations of Down syndrome are the characteristic
   facial features, cognitive impairment, congenital heart disease,
   hearing deficits, short stature, thyroid disorders, and Alzheimer's
   disease. Other less common serious illnesses include leukemia, immune
   deficiencies, and epilepsy. Down syndrome can result from several
   different genetic mechanisms. This results in a wide variability in
   individual symptoms due to complex gene and environment interactions.
   Prior to birth, it is not possible to predict the symptoms that an
   individual with Down syndrome will develop. Some problems are present
   at birth, such as certain heart malformations. Others become apparent
   over time, such as epilepsy.

   These factors can contribute to a significantly shorter lifespan for
   people with Down syndrome. One study, carried out in the United States
   in 2002, showed an average lifespan of 49 years.

Genetic research

   Down syndrome disorders are based on having too many copies of the
   genes located on chromosome 21. In general, this leads to an
   overexpression of the genes. Understanding the genes involved may help
   to target medical treatment to individuals with Down syndrome. It is
   estimated that chromosome 21 contains 200 to 250 genes. Recent research
   has identified a region of the chromosome that contains the main genes
   responsible for the pathogenesis of Down syndrome, located proximal to
   21q22.3. The search for major genes involved in Down syndrome
   characteristics is normally in the region 21q21–21q22.3.

   Recent use of transgenic mice to study specific genes in the Down
   syndrome critical region has yielded some results. APP is an Amyloid
   beta A4 precursor protein. It is suspected to have a major role in
   cognitive difficulties. Another gene, ETS2 is Avian Erythroblastosis
   Virus E26 Oncogene Homolog 2. Researchers have "demonstrated that
   overexpression of ETS2 results in apoptosis. Transgenic mice
   overexpressing ETS2 developed a smaller thymus and lymphocyte
   abnormalities, similar to features observed in Down syndrome."

Sociological and cultural aspects

   Advocates for people with Down syndrome point to various factors, such
   as special education and parental support groups, that make life easier
   for parents. There are also strides being made in education, housing,
   and social settings to create "DS-friendly" environments. In most
   developed countries, since the early twentieth century many people with
   Down syndrome were housed in institutions or colonies and excluded from
   society. However, in the twenty-first century there is a change among
   parents, educators and other professionals generally advocating a
   policy of inclusion, bringing people with any form of mental or
   physical disability into general society as much as possible. In many
   countries, people with Down syndrome are educated in the normal school
   system; there are increasingly higher-quality opportunities to mix
   special education with regular education settings

   Despite this change, reduced abilities of people with Down syndrome can
   pose a challenge to parents and families. Although living with family
   is preferable to institutionalization for most people, people with Down
   syndrome often encounter patronising attitudes and discrimination in
   the wider community. In the past decade, many couples with Down
   syndrome have married and started families, overcoming stereotypes
   associated with this condition.

   The first World Down Syndrome Day was held on 21 March 2006. The day
   and month were chosen to correspond with 21 and trisomy respectively.
   It was proclaimed by Down Syndrome International.

History

   English physician John Langdon Down first characterized Down syndrome
   as a distinct form of mental retardation in 1862, and in a more widely
   published report in 1866 entitled "Observations on an ethnic
   classification of idiots". Due to his perception that children with
   Down syndrome shared physical facial similarities ( epicanthal folds)
   with those of Blumenbach's Mongolian race, Down used terms such as
   mongolism and Mongolian idiocy. Idiocy was a medical term used at that
   time to refer to a severe degree of intellectual impairment. Down wrote
   that mongolism represented "retrogression," the appearance of Mongoloid
   traits in the children of allegedly more advanced Caucasian parents.

   John Langdon Down was ambivalent about Darwinism and uncomfortable that
   it was being used by some (though not by Darwin himself) to justify
   racial discrimination. Langdon Down was himself of the opinion that the
   human race was universal and he stated that "these examples of the
   results of degeneracy among mankind appear to me to furnish some
   arguments in favour of the unity of the human species."

   Professor O'Connor Ward states in his book 'Dr John Langdon Down And
   Normansfield' (updated and reprinted 2006) that: "After his initial
   identification of the specific picture of the Mongolian Idiot, Langdon
   Down moved away from the concept of facial and other characteristics of
   other races representing evidence of degenerative genetic inheritance,
   leading to physical characteristics appropriate to another racial
   stock. Speaking in a discussion on a paper by B.W. Richardson in 1867
   on 'Physical Disease from Mental Strain', Langdon Down said that he had
   abandoned his belief in phrenology after 10 years of study. He had
   turned his back on the view that a person's character and intelligence
   could be deduced from the outer appearance and shape of the skull. They
   could estimate quantity of the brain, but owing to not being able to
   ascertain the quality on the failure of phrenology, which had received
   due attention from those who paid great attention to psychiatric
   subjects and had been tried and found wanting."

   When Langdon Down was invited to write for the section on idiocy in
   Quain's Dictionary of Medicine in 1882, he made no mention of racial
   characteristics as being important in the diagnosis. His Mongolian
   group were simply listed as strumous. He had, for practical purposes,
   abandoned the ethnic concept. The dictionary appeared again in 1894 and
   once more Langdon Down wrote the section on idiocy. He again left the
   ethnic concept in abeyance.' Citation: Stuart Mills, Information
   Officer, http://www.downs-syndrome.org.uk/

   By the 20^th century, "Mongolian idiocy" had become the most
   recognizable form of mental retardation. Most individuals with Down
   syndrome were institutionalized, few of the associated medical problems
   were treated, and most died in infancy or early adult life. With the
   rise of the eugenics movement, 33 of the (then) 48 U.S. states and
   several countries began programs of involuntary sterilization of
   individuals with Down syndrome and comparable degrees of disability.
   The ultimate expression of this type of public policy was the German
   euthanasia program "Aktion T-4", begun in 1940. Court challenges and
   public revulsion led to discontinuation or repeal of such programs
   during the decades after World War II.

   Until the middle of the 20th century, the cause of Down syndrome
   remained unknown. However, the presence in all races, the association
   with older maternal age, and the rarity of recurrence had been noticed.
   Standard medical texts assumed it was caused by a combination of
   inheritable factors which had not been identified. Other theories
   focused on injuries sustained during birth.

   With the discovery of karyotype techniques in the 1950s, it became
   possible to identify abnormalities of chromosomal number or shape. In
   1959, Professor Jérôme Lejeune discovered that Down syndrome resulted
   from an extra chromosome. The extra chromosome was subsequently labeled
   as the 21st, and the condition as trisomy 21.

   In 1961, nineteen geneticists wrote to the editor of The Lancet
   suggesting that Mongolian idiocy had "misleading connotations," had
   become "an embarrassing term," and should be changed. The Lancet
   supported Down's Syndrome. The World Health Organization (WHO)
   officially dropped references to mongolism in 1965 after a request by
   the Mongolian delegate.

   In 1975, the United States National Institute of Health convened a
   conference to standardize the nomenclature of malformations. They
   recommended eliminating the possessive form: "The possessive use of an
   eponym should be discontinued, since the author neither had nor owned
   the disorder." Although both the possessive and non-possessive forms
   are used in the general population, Down syndrome is the accepted term
   among professionals in the USA, Canada and other countries; Down's
   syndrome is still used in the United Kingdom and other areas.

Notable individuals

   Notable people with Down syndrome include:
     * Chris Burke, actor ( Life Goes On) and autobiographer
     * Anne de Gaulle (1928-1948), daughter of Charles de Gaulle
     * Stephane Ginnsz, actor ( Duo) — first actor with Down syndrome in
       the lead part of a motion picture.
     * Joey Moss, Edmonton Oilers locker room attendant
     * Isabella Pujols, adopted daughter of St. Louis Cardinals first
       baseman Albert Pujols
     * Judith Scott, artist
     * Johnny Stallings, son of former University of Alabama head football
       coach Gene Stallings and subject of the book Another Season ( ISBN
       0767902556).
     * Miguel Tomasin, singer with Argentinian avant-rock band Reynols

   The Down Syndrome Association of Los Angeles maintains a list of
   individuals with Down syndrome in roles in TV and movies.

Portrayal in fiction

     * Bret Lott: Jewel
     * Bernice Rubens: A Solitary Grief
     * Paul M Belous & Robert Wolterstorff: Quantum Leap: Jimmy
     * Emily Perl Kingsley: Welcome to Holland
     * The Kingdom and its American counterpart, Kingdom Hospital
     * Stephen King: Dreamcatcher
     * Dean Koontz: The Bad Place
     * Jeffrey Eugenides: The Virgin Suicides
     * Petal Mitchell, character in EastEnders
     * Kim Edwards: The Memory Keeper's Daughter
     * June Rae Wood: The Man Who Loved Clowns

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