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 [2]

Down syndrome (the most common term in US English), Down's syndrome (standard in the
rest of the English-speaking world), trisomy 21, or trisomy G is a chromosomal 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 described the syndrome in 1866. The disorder was identified as a
chromosome 21 trisomy by Jérôme Lejeune in 1959. The condition is characterized by a
combination of major and minor differences in structure. Often Down syndrome is associated
with some impairment of cognitive ability and physical growth as well as facial appearance.
Down syndrome in a baby can be identified with amniocentesis during pregnancy or at birth.
Individuals with Down syndrome tend to have a lower than average cognitive ability, often
ranging from mild to moderate developmental disabilities. A small number have severe to
profound mental disability. The incidence of Down syndrome is estimated at 1 per 800 to 1,000
births, although these statistics are heavily influenced by older mothers. Other factors may also
play a role.
Many of the common physical features of Down syndrome may also appear in people with a
standard set of chromosomes, including microgenia (an abnormally small chin)[1], an unusually
round face, macroglossia[2] (protruding or oversized tongue), an almond shape to the eyes caused
by an epicanthic fold of the eyelid, upslanting palpebral fissures (the separation between the
upper and lower eyelids), shorter limbs, a single transverse palmar crease (a single instead of a
double crease across one or both palms, also called the Simian crease), poor muscle tone, and a
larger than normal space between the big and second toes. 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.[3]

Contents
[hide]
• 1 Characteristics
○ 1.1 Cognitive development
○ 1.2 Fertility
• 2 Genetics
○ 2.1 Trisomy 21
○ 2.2 Mosaicism
○ 2.3 Robertsonian translocation
○ 2.4 Duplication of a portion of chromosome 21
• 3 Screening
○ 3.1 Ethical issues
• 4 Management
○ 4.1 Plastic surgery
○ 4.2 Alternative treatment
• 5 Prognosis
• 6 Epidemiology
 • 7 History
• 8 Society and culture
○ 8.1 Notable individuals
○ 8.2 Portrayal in fiction
• 9 Research
• 10 Footnotes
• 11 References
○ 11.1 Research bibliography
○ 11.2 General bibliography
• 12 External links

Characteristics
Main article: Health aspects of Down syndrome

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:
microgenia (abnormally small chin)[1], oblique eye fissures with epicanthic skin folds on the
inner corner of the eyes (formerly known as a mongoloid fold[2]), muscle hypotonia (poor muscle
tone), a flat nasal bridge, a single palmar fold, a protruding tongue (due to small oral cavity, and
an enlarged tongue near the tonsils) or macroglossia[2], a short neck, white spots on the iris
known as Brushfield spots,[4] excessive joint laxity including atlanto-axial instability, congenital
heart defects, excessive space between large toe and second toe, a single flexion furrow of the
fifth finger, and a higher number of ulnar loop dermatoglyphs. Most individuals with Down
syndrome have mental retardation in the mild (IQ 50–70) to moderate (IQ 35–50) range,[5] with
individuals having Mosaic Down syndrome typically 10–30 points higher.[6] In addition,
individuals with Down syndrome can have serious abnormalities affecting any body system.
They also may have a broad head and a very round face.
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.[5]
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.
The most common manifestations of Down syndrome are the characteristic facial features,
cognitive impairment, congenital heart disease (typically a ventricular septal defect), hearing
deficits (maybe due to sensory-neural factors, or chronic serous otitis media, also known as
Glue-ear), short stature, thyroid disorders, and Alzheimer's disease. Other less common serious
illnesses include leukemia, immune deficiencies, and epilepsy.
However, health benefits of Down syndrome include greatly reduced incidence of many
common malignancies except leukemia and testicular cancer[7] — although it is, as yet, unclear
whether the reduced incidence of various fatal cancers among people with Down syndrome is as
a direct result of tumor-suppressor genes on chromosome 21 (such as Ets2),[8] because of reduced
exposure to environmental factors that contribute to cancer risk, or some other as-yet unspecified
factor. In addition to a reduced risk of most kinds of cancer, people with Down syndrome also
have a much lower risk of hardening of the arteries and diabetic retinopathy.[8]
Cognitive development
Cognitive development in children with Down syndrome is quite variable. It is not currently
possible at birth to predict the capabilities of any individual reliably, nor are the number or
appearance of physical features predictive of future ability. The identification of the best
methods of teaching each particular child ideally begins soon after birth through early
intervention programs.[9] Since children with Down syndrome have a wide range of abilities,
success at school can vary greatly, which underlines 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, and
commonly individuals with Down syndrome have a speech delay, requiring speech therapy to
improve expressive language.[10] Fine motor skills are delayed[11] and often lag behind gross
motor skills and can interfere with cognitive development. Effects of the disorder on the
development of gross motor skills are quite variable. Some children will begin walking at around
2 years of age, while others will not walk until age 4. Physical therapy, and/or participation in a
program of adapted physical education (APE), may promote enhanced development of gross
motor skills in Down syndrome children.[12]
Individuals with Down syndrome differ considerably in their language and communication skills.
It is routine to screen for middle ear problems and hearing loss; low gain hearing aids or other
amplification devices can be useful for language learning. Early communication intervention
fosters linguistic skills. Language assessments can help profile strengths and weaknesses; for
example, it is common for receptive language skills to exceed expressive skills. Individualized
speech therapy can target specific speech errors, increase speech intelligibility, and in some cases
encourage advanced language and literacy. Augmentative and alternative communication (AAC)
methods, such as pointing, body language, objects, or graphics are often used to aid
communication. Relatively little research has focused on the effectiveness of communications
intervention strategies.[13]
In education, mainstreaming of children with Down syndrome is becoming less controversial in
many countries. For example, there is a presumption of mainstream in many parts of the UK.
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 the abilities of some, 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.[14]
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 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.[15]
Fertility
Fertility amongst both males and females is reduced; males are usually unable to father children,
while females demonstrate significantly lower rates of conception relative to unaffected
individuals.[citation needed] Approximately half of the offspring of someone with Down syndrome also
have the syndrome themselves.[16] There have been only three recorded instances of males with
Down syndrome fathering children.[17][18]
Genetics
Main article: Genetic origins of Down syndrome

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 people, depending on the extent
of the extra copy, genetic history, and pure chance. Down syndrome occurs in all human
populations, and analogous effects have been found in other species such as chimpanzees[19] and
mice. Recently, researchers have created transgenic mice with most of human chromosome 21
(in addition to the normal mouse chromosomes).[20] The extra chromosomal material can come
about in several distinct ways. A typical human karyotype is designated as 46,XX or 46,XY,
indicating 46 chromosomes with an XX arrangement typical of females and 46 chromosomes
with an XY arrangement typical of males.[21]
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.[22]
Mosaicism
Trisomy 21 is usually caused by nondisjunction in the gametes 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).[23][24] 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 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.[22]
Robertsonian translocation
The extra chromosome 21 material that causes Down syndrome may be due to a Robertsonian
translocation in the karyotype of one of the parents. 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)). A person with such a translocation is phenotypically
normal. During reproduction, normal disjunctions leading to gametes have a significant chance
of creating a gamete with an extra chromosome 21, producing a child with Down syndrome.
Translocation Down syndrome is often referred to as familial Down syndrome. It is the cause of
2–3% of observed cases of Down syndrome.[22] 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)).[25] 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.
Screening

Ultrasound of fetus with Down syndrome and megacystis

Pregnant women can be screened for various complications during pregnancy. Many standard
prenatal screens can discover Down syndrome. Genetic counseling along with genetic testing,
such as amniocentesis, chorionic villus sampling (CVS), or percutaneous umbilical cord 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. In the
United States, ACOG guidelines recommend that non-invasive screening and invasive testing be
offered to all women, regardless of their age, and most likely all physicians currently follow
these guidelines. However, some insurance plans will only reimburse invasive testing if a woman
is >34 years old or if she has received a high-risk score from a non-invasive screening test.
Amniocentesis and CVS are considered invasive procedures, in that they involve inserting
instruments into the uterus, and therefore carry a small risk of causing fetal injury or miscarriage.
The risks of miscarriage for CVS and amniocentesis are often quoted as 1% and 0.5%
respectively. There are several common non-invasive screens that can indicate a fetus with Down
syndrome. These 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.

Table 1: First and second trimester Down syndrome screens

When
False
performed Detection
Screen positive Description
(weeks rate
rate
gestation)

This test measures the maternal serum

alpha feto protein (a fetal liver
protein), estriol (a pregnancy
Quad screen 15–20 81%[8] 5% hormone), human chorionic
gonadotropin (hCG, a pregnancy
hormone), and inhibin-Alpha
(INHA).[26]

Nuchal 10–13.5 85%[27] 5% Uses ultrasound to measure Nuchal

translucency/free Translucency in addition to the
beta/PAPPA screen freeBeta hCG and PAPPA
(aka "1st Trimester (pregnancy-associated plasma protein
Combined Test") A). NIH has confirmed that this first
trimester test is more accurate than
second trimester screening methods.
[28]
Performing an NT ultrasound
requires considerable skill; a
Combined test may be less accurate if
 there is operator error, resulting in a
lower-than-advertised sensitivity and
higher false-positive rate, possibly in
the 5-10% range.

The Integrated test uses

measurements from both the 1st
Trimester Combined test and the 2nd
trimester Quad test to yield a more
10-13.5 and accurate screening result. Because all
Integrated Test 95%[29] 5%
15–20 of these tests are dependent on
accurate calculation of the gestational
age of the fetus, the real-world false-
positive rate is >5% and maybe be
closer to 7.5%.

Even with the best non-invasive screens, the detection rate is 90%–95% and the rate of false
positive is 2%–5%. Inaccuracies 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 or chorionic villus
sampling (CVS). Amniocentesis is an invasive procedure and involves taking amniotic fluid
from the amniotic sac and identifying fetal cells. The lab work can take several weeks but will
detect over 99.8% of all numerical chromosomal problems with a very low false positive rate.[30]
Ethical issues
A 2002 literature review of elective abortion rates found that 91–93% of pregnancies in the
United States with a diagnosis of Down syndrome were terminated.[31] Data from the National
Down Syndrome Cytogenetic Register in the United Kingdom indicates that from 1989 to 2006
the proportion of women choosing to terminate a pregnancy following prenatal diagnosis of
Down Syndrome has remained constant at around 92%.[32][33] Physicians and ethicists are
concerned about the ethical ramifications of this.[34] Conservative commentator George Will
called it "eugenics by abortion".[35] British peer Lord Rix stated that "alas, the birth of a child
with Down's syndrome is still considered by many to be an utter tragedy" and that the "ghost of
the biologist Sir Francis Galton, who founded the eugenics movement in 1885, still stalks the
corridors of many a teaching hospital".[36] Doctor David Mortimer has argued in Ethics &
Medicine that "Down's syndrome infants have long been disparaged by some doctors and
government bean counters."[37] Some 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."[38]
Management
Treatment of individuals with Down Syndrome depends on the particular manifestations of the
disease. For instance, individuals with congenital heart disease may need to undergo major
corrective surgery soon after birth. Other individuals may have relatively minor health problems
requiring no therapy.
Plastic surgery
Plastic surgery has sometimes been advocated and performed on children with Down syndrome,
based on the assumption that surgery can reduce the facial features associated with Down
syndrome, therefore decreasing social stigma, and leading to a better quality of life.[39] Plastic
surgery on children with Down syndrome is uncommon,[40] and continues to be controversial.
Researchers have found that for facial reconstruction, "...although most patients reported
improvements in their child's speech and appearance, independent raters could not readily
discern improvement...."[41] For partial glossectomy (tongue reduction), one researcher found that
1 out of 3 patients "achieved oral competence," with 2 out of 3 showing speech improvement.[42]
Len Leshin, physician and author of the ds-health website, has stated, "Despite being in use for
over twenty years, there is still not a lot of solid evidence in favor of the use of plastic surgery in
children with Down syndrome."[43] The National Down Syndrome Society has issued a "Position
Statement on Cosmetic Surgery for Children with Down Syndrome"[44] which states that "The
goal of inclusion and acceptance is mutual respect based on who we are as individuals, not how
we look."
Alternative treatment
See also: Alternative therapies for developmental and learning disabilities
The Institutes for the Achievement of Human Potential is a non-profit organization which treats
children who have, as the IAHP terms it, "some form of brain injury," including children with
Down syndrome. The approach of "Psychomotor Patterning" is not proven,[45] and is considered
alternative medicine.
Prognosis
These factors can contribute to a shorter life expectancy for people with Down syndrome. One
study, carried out in the United States in 2002, showed an average lifespan of 49 years, with
considerable variations between different ethnic and socio-economic groups.[46] However, in
recent decades, the life expectancy among persons with Down syndrome has increased
significantly up from 25 years in 1980. The causes of death have also changed, with chronic
neurodegenerative diseases becoming more common as the population ages. Most people with
Down Syndrome who survive into their 40s and 50s begin to suffer from an alzheimer's-like
dementia.[47]
Epidemiology

Graph showing probability of Down syndrome as a function of maternal age.

The incidence of Down syndrome is estimated at one per 800 to one per 1000 births.[48] In 2006,
the Centers for Disease Control and Prevention estimated the rate as one per 733 live births in
the United States (5429 new cases per year).[49] Approximately 95% of these are trisomy 21.
Down syndrome occurs in all ethnic groups and among all economic classes.
Maternal age influences the chances of conceiving a baby with Down syndrome. At maternal age
20 to 24, the probability is one in 1562; at age 35 to 39 the probability is one in 214, and above
age 45 the probability is one in 19.[50] Although the probability increases with maternal age, 80%
of children with Down syndrome are born to women under the age of 35,[51] reflecting the overall
fertility of that age group. Recent data also suggest that paternal age, especially beyond 42,[52]
also increases the risk of Down Syndrome manifesting in pregnancies in older mothers.[53]
Current research (as of 2008) has shown that Down syndrome is due to a random event during
the formation of sex cells or pregnancy. There has been no evidence that it is due to parental
behavior (other than age) or environmental factors.
History
English physician John Langdon Down first characterized Down syndrome as a distinct form of
mental disability in 1862, and in a more widely published report in 1866.[54] Due to his
perception that children with Down syndrome shared physical facial similarities (epicanthal
folds) with those of Blumenbach's Mongolian race, Down used the term mongoloid, derived
from prevailing ethnic theory.[55] Attitudes to Down's syndrome were very much tied to racism
until as recently as the 1970's.
By the 20th century, Down syndrome had become the most recognizable form of mental
disability. 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
forced sterilization of individuals with Down syndrome and comparable degrees of disability.
The ultimate expression of this type of public policy was "Action T4" in Nazi Germany, a
program of systematic murder. Court challenges, scientific advances and public revulsion led to
discontinuation or repeal of such sterilization 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.
[56]

With the discovery of karyotype techniques in the 1950s, it became possible to identify
abnormalities of chromosomal number or shape. In 1959, Jérôme Lejeune discovered that Down
syndrome resulted from an extra chromosome.[57][58] The extra chromosome was subsequently
labeled as the 21st, and the condition as trisomy 21.
In 1961, eighteen geneticists wrote to the editor of The Lancet suggesting that Mongolian idiocy
had "misleading connotations," had become "an embarrassing term," and should be changed.[59]
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.[60] However,
almost 40 years later, the term ‘mongolism’ still appears in leading medical texts such as
General and Systematic Pathology, 4th Edition, 2004, edited by Professor Sir James Underwood.
In 1975, the United States National Institutes 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."[61] 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.[62]
Society and culture
Advocates for people with Down syndrome point to various factors, such as additional
educational support and parental support groups to improve parenting knowledge and skills.
There are also strides being made in education, housing, and social settings to create
environments which are accessible and supportive to people with Down syndrome. 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, since the early 1960s
parents and their organizations (such as MENCAP), educators and other professionals have
generally advocated a policy of inclusion,[63] 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 move from special (segregated) education to regular education settings.
Despite these changes, the additional support needs of people with Down syndrome can still pose
a challenge to parents and families. Although living with family is preferable to
institutionalization, people with Down syndrome often encounter patronizing attitudes and
discrimination in the wider community.
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 European Down
Syndrome Association during their European congress in Palma de Mallorca (febr. 2005). In the
United States, the National Down Syndrome Society observes Down Syndrome Month every
October as "a forum for dispelling stereotypes, providing accurate information, and raising
awareness of the potential of individuals with Down syndrome."[64] In South Africa, Down
Syndrome Awareness Day is held every October 20.[65] Organizations such as Special Olympics
Hawaii provide year-round sports training for individuals with intellectual disabilities such as
down syndrome.
Notable individuals
Scottish award-winning film and TV actress Paula Sage receives her BAFTA award with Brian
Cox.
• Stephane Ginnsz, actor (Duo)—In 1996 was first actor with Down syndrome in the lead
part of a motion picture.[66]
• Joey Moss, Edmonton Oilers locker room attendant.[67]
• Isabella Pujols, adopted daughter of St. Louis Cardinals first baseman Albert Pujols and
inspiration for the Pujols Family Foundation.[68]
• Paula Sage, Scottish film actress and Special Olympics netball athlete.[69] Her role in the
2003 film AfterLife brought her a BAFTA Scotland award for best first time performance
and Best Actress in the Bratislava International Film Festival, 2004.[70]
• Chris Burke, American actor who portrayed "Corky Thatcher" on the television series
Life Goes On and "Taylor" on Touched By An Angel.
• Edward Barbanell, played Billy in 2005's The Ringer.
• Danny Alsabbagh, Australian actor who played Toby in the Australian mockumentary
series Summer Heights High
• Tommy Jessop, British actor who played Ben in Coming Down the Mountain, opposite
Nicholas Hoult
• Rene Moreno, subject of "Up Syndrome" - a documentary film about life with Down
syndrome.[71][72]
• Nigel Hunt, British author (The World Of Nigel Hunt; The Diary Of A Mongoloid Youth
-- this book was published in 1967, when "mongoloid" was still quite commonly used to
refer to people with Down's Syndrome).
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
• Theodore Sturgeon: More Than Human
• Janet Mitchell, character in EastEnders
• Kim Edwards: The Memory Keeper's Daughter
• June Rae Wood: The Man Who Loved Clowns
• Jaco van Dormael: Le huitième jour
• Mark Haddon: Coming Down the Mountain (BBC Radio play and BBC TV Drama)
• Theodore "T-Bag" Bagwell's mother: Prison Break
 • Chris Burke as Charles "Corky" Thatcher in Life Goes On
• "Toby": Summer Heights High
Research
Main article: Research of Down syndrome-related genes
Down syndrome is “a developmental abnormality characterized by trisomy of human
chromosome 21" (Nelson 619). The extra copy of chromosome-21 leads to an over expression of
certain genes located on chromosome-21.
Research by Arron et al. shows that some of the phenotypes associated with Down syndrome can
be related to the disregulation of transcription factors (596), and in particular, NFAT. NFAT is
controlled in part by two proteins, DSCR1 and DYRK1A; these genes are located on
chromosome-21 (Epstein 582). In people with Down syndrome, these proteins have 1.5 times
greater concentration than normal (Arron et al. 597). The elevated levels of DSCR1 and
DYRK1A keep NFAT primarily located in the cytoplasm rather than in the nucleus, preventing
NFATc from activating the transcription of target genes and thus the production of certain
proteins (Epstein 583).
This dysregulation was discovered by testing in transgenic mice that had segments of their
chromosomes duplicated to simulate a human chromosome-21 trisomy (Arron et al. 597). A test
involving grip strength showed that the genetically modified mice had a significantly weaker
grip, much like the characteristically poor muscle tone of an individual with Down syndrome
(Arron et al. 596). The mice squeezed a probe with a paw and displayed a .2 newton weaker grip
(Arron et al. 596). Down syndrome is also characterized by increased socialization. When
modified and unmodified mice were observed for social interaction, the modified mice showed
as much as 25% more interactions as compared to the unmodified mice (Arron et al. 596).
The genes that may be responsible for the phenotypes associated may be located proximal to
21q22.3. Testing by Olson et al. in transgenic mice show the duplicated genes presumed to cause
the phenotypes are not enough to cause the exact features. While the mice had sections of
multiple genes duplicated to approximate a human chromosome-21 triplication, they only
showed slight craniofacial abnormalities (688-690). The transgenic mice were compared to mice
that had no gene duplication by measuring distances on various points on their skeletal structure
and comparing them to the normal mice (Olson et al. 687). The exact characteristics of Down
syndrome were not observed, so more genes involved for Down Syndrome phenotypes have to
be located elsewhere.
Reeves et al., using 250 clones of chromosome-21 and specific gene markers, were able to map
the gene in mutated bacteria. The testing had 99.7% coverage of the gene with 99.9995%
accuracy due to multiple redundancies in the mapping techniques. In the study 225 genes were
identified (311-313).
The search for major genes that may be involved in Down syndrome symptoms is normally in
the region 21q21–21q22.3. However, studies by Reeves et al. show that 41% of the genes on
chromosome-21 have no functional purpose, and only 54% of functional genes have a known
protein sequence. Functionality of genes was determined by a computer using exon prediction
analysis (312). Exon sequence was obtained by the same procedures of the chromosome-21
mapping.
Research has led to an understanding that two genes located on chromosome-21, that code for
proteins that control gene regulators, DSCR1 and DYRK1A can be responsible for some of the
phenotypes associated with Down syndrome. DSCR1 and DYRK1A cannot be blamed outright
for the symptoms; there are a lot of genes that have no known purpose. Much more research
would be needed to produce any appropriate or ethically acceptable treatment options.
Recent use of transgenic mice to study specific genes in the Down syndrome critical region has
yielded some results. APP[73] is an Amyloid beta A4 precursor protein. It is suspected to have a
major role in cognitive difficulties.[74] Another gene, ETS2[75] is Avian Erythroblastosis Virus
E26 Oncogene Homolog 2. Researchers have "demonstrated that over-expression of ETS2
results in apoptosis. Transgenic mice over-expressing ETS2 developed a smaller thymus and
lymphocyte abnormalities, similar to features observed in Down syndrome."[75]
Vitamin supplements, in particular supplemental antioxidants and folinic acid, have been shown
to be ineffective in the treatment of Down syndrome.[76]
Footnotes
1. ^ a b Meira Weiss. "Conditional love: parents' attitudes toward handicapped children". p. page 94.
http://books.google.com/books?id=a62J5GPHd3cC&pg=PA94&lpg=PA94&dq=%22down
%27s+syndrome
%22+chin+face&source=bl&ots=hVCgwMgpKi&sig=dZ3TYZnWjWMEnTioJY9WQcLP_4E&
hl=en&ei=0Q9nSsegJYOZjAe6ypmmAQ&sa=X&oi=book_result&ct=result&resnum=5.
Retrieved 2009-07-22.
2. ^ a b c This discussion by Myron Belfer, M.D., book by Gottfried Lemperie, M.D., and Dorin
Radu, M.D. (1980). "Facial Plastic Surgery in Children with Down's Syndrome (preview page,
with link to full content on plasreconsurg.com)". p. page 343. http://scholar.google.com/scholar?
q=info:Nt6asksVAiYJ:scholar.google.com/&hl=en&output=viewport. Retrieved 2009-07-22.
3. ^ Roizen NJ, Patterson D.Down's syndrome. Lancet. 2003 12 April;361(9365):1281–9. Review.
PMID 12699967
4. ^ "Definition of Brushfield's Spots". http://www.medterms.com/script/main/art.asp?
articlekey=6570.
5. ^ a b American Academy of Pediatrics Committee on Genetics (February 2001). "American
Academy of Pediatrics: Health supervision for children with Down syndrome". Pediatrics 107
(2): 442–449. doi:10.1542/peds.107.2.442. PMID 11158488.
6. ^ Strom, C. "FAQ from Mosaic Down Syndrome Society".
http://www.mosaicdownsyndrome.com/faqs.htm. Retrieved 2006-06-03.
7. ^ Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA
from 1983 to 1997: a population-based study. Lancet 2002 23 March;359(9311):1019–25. PMID
11937181
8. ^ a b c [1][dead link]
9. ^ "Dear New or Expectant Parents". National Down Syndrome Society.
http://www.ndss.org/index.php?option=com_content&task=view&id=2015&Itemid=198.
Retrieved 2006-05-12. Also "Research projects - Early intervention and education".
http://www.downsed.org/topics/early-intervention/. Retrieved 2006-06-02.
10.^ Bird, G. and S. Thomas (2002). "Providing effective speech and language therapy for children
with Down syndrome in mainstream settings: A case example". Down Syndrome News and
Update 2 (1): 30–31. Also, Kumin, Libby (1998). "Comprehensive speech and language
treatment for infants, toddlers, and children with Down syndrome". in Hassold, T.J.and D.
Patterson. Down Syndrome: A Promising Future, Together. New York: Wiley-Liss.
11.^ "Development of Fine Motor Skills in Down Syndrome". http://www.about-down-
syndrome.com/fine-motor-skills-in-down-syndrome.html. Retrieved 2006-07-03.
12.^ M. Bruni. "Occupational Therapy and the Child with Down Syndrome". http://www.ds-
health.com/occther.htm. Retrieved 2006-06-02.
13.^ Roberts JE, Price J, Malkin C (2007). "Language and communication development in Down
syndrome". Ment Retard Dev Disabil Res Rev 13 (1): 26–35. doi:10.1002/mrdd.20136. PMID
17326116.
14.^ S.E.Armstrong. "Inclusion: Educating Students with Down Syndrome with Their Non-Disabled
Peers". http://www.altonweb.com/cs/downsyndrome/index.htm?page=ndssincl.html. Retrieved
2006-05-12. Also, see Debra L. Bosworth. "Benefits to Students with Down Syndrome in the
Inclusion Classroom: K-3". http://www.altonweb.com/cs/downsyndrome/index.htm?
page=bosworth.html. Retrieved 2006-06-12. Finally, see a survey by NDSS on inclusion, Gloria
Wolpert (1996). "The Educational Challenges Inclusion Study". National Down Syndrome
Society. http://www.altonweb.com/cs/downsyndrome/index.htm?page=wolpert.html. Retrieved
2006-06-28.
15.^ There are many such programs. One is described by Action Alliance for Children, K. Flores.
"Special needs, "mainstream" classroom". http://www.4children.org/news/103spec.htm.
Retrieved 2006-05-13. Also, see Flores, K.. "Special needs, "mainstream" classroom".
http://www.4children.org/pdf/103spec.pdf. Retrieved 2006-05-13.
16.^ Hsiang YH, Berkovitz GD, Bland GL, Migeon CJ, Warren AC (1987). "Gonadal function in
patients with Down syndrome". Am. J. Med. Genet. 27 (2): 449–58.
doi:10.1002/ajmg.1320270223. PMID 2955699.
17.^ Sheridan R, Llerena J, Matkins S, Debenham P, Cawood A, Bobrow M (1989). "Fertility in a
male with trisomy 21". J Med Genet 26 (5): 294–8. doi:10.1136/jmg.26.5.294. PMID 2567354.
18.^ Pradhan M, Dalal A, Khan F, Agrawal S (2006). "Fertility in men with Down syndrome: a case
report". Fertil Steril 86 (6): 1765.e1–3. doi:10.1016/j.fertnstert.2006.03.071. PMID 17094988.
19.^ McClure HM, Belden KH, Pieper WA, Jacobson CB. Autosomal trisomy in a chimpanzee:
resemblance to Down's syndrome. Science. 1969 5 September;165(897):1010–2. PMID 4240970
20.^ "Down's syndrome recreated in mice". BBC News. 2005-09-22.
http://news.bbc.co.uk/1/hi/health/4268226.stm. Retrieved 2006-06-14.
21.^ For a description of human karyotype see Mittleman, A. (editor) (1995). "An International
System for Human Cytogenetic Nomeclature". http://www.iscn1995.org/. Retrieved 2006-06-04.
22.^ a b c "Down syndrome occurrence rates (NIH)".
http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#TheOccurrence. Retrieved
2006-06-02.
23.^ Mosaic Down syndrome on the Web
24.^ International Mosaic Down syndrome Association
25.^ Petersen MB, Tranebjaerg L, McCormick MK, Michelsen N, Mikkelsen M, Antonarakis SE.
Clinical, cytogenetic, and molecular genetic characterization of two unrelated patients with
different duplications of 21q. Am J Med Genet Suppl. 1990;7:104-9. PMID 2149934
26.^ For a current estimate of rates, see Benn, PA, J Ying, T Beazoglou, JFX Egan (2001).
"Estimates for the sensitivity and false-positive rates for second trimester serum screening for
Down syndrome and trisomy 18 with adjustments for cross-identification and double-positive
results". Prenatal Diagnosis 21 (1): 46–51. doi:10.1002/1097-0223(200101)21:1<46::AID-
PD984>3.0.CO;2-C. PMID 11180240
27.^ ACOG Guidelines Bulletin #77 state that the sensitivity of the Combined Test is 82-87%
28.^ NIH FASTER study (NEJM 2005 (353):2001). See also J.L. Simplson's editorial (NEJM 2005
(353):19).
29.^ ACOG Guidelines Bulletin #77 state that the sensitivity of the Integrated Test is 94-96%
30.^ Fackler, A. "Down syndrome".
http://health.yahoo.com/topic/children/baby/article/healthwise/hw167989. Retrieved 2006-09-07.
31.^ Caroline Mansfield, Suellen Hopfer, Theresa M. Marteau (1999). "Termination rates after
prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter
syndromes: a systematic literature review". Prenatal Diagnosis 19 (9): 808–812. doi:10.1002/
(SICI)1097-0223(199909)19:9<808::AID-PD637>3.0.CO;2-B.
http://www3.interscience.wiley.com/cgi-bin/abstract/65500197/ABSTRACT. PMID 10521836
This is similar to 90% results found by David W. Britt, Samantha T. Risinger, Virginia Miller,
Mary K. Mans, Eric L. Krivchenia, Mark I. Evans (1999). "Determinants of parental decisions
after the prenatal diagnosis of Down syndrome: Bringing in context". American Journal of
Medical Genetics 93 (5): 410–416. doi:10.1002/1096-8628(20000828)93:5<410::AID-
AJMG12>3.0.CO;2-F. PMID 10951466
32.^ "Society 'more positive on Down's'". BBC News. 2008-11-24.
http://news.bbc.co.uk/1/hi/health/7746747.stm.
33.^ Peter Horrocks (2008-12-05). "Changing attitudes?". BBC News.
http://www.bbc.co.uk/blogs/theeditors/2008/12/changing_attitudes.html.
34.^ Glover, NM and Glover, SJ (1996). "Ethical and legal issues regarding selective abortion of
fetuses with Down syndrome". Ment. Retard. 34 (4): 207–214. PMID 8828339.
35.^ Will, George (2005-04-01). "Eugenics By Abortion: Is perfection an entitlement?". Washington
Post: A37. http://www.washingtonpost.com/wp-dyn/articles/A51671-2005Apr13.html.
36.^ Letter: Ghost of eugenics stalks Down's babies | Independent, The (London) | Find Articles at
BNET.com
37.^ New Eugenics and the newborn: The historical "cousinage" of eugenics and infanticide, The |
Ethics & Medicine | Find Articles at BNET.com
38.^ Erik Parens and Adrienne Asch (2003). "Disability rights critique of prenatal genetic testing:
Reflections and recommendations". Mental Retardation and Developmental Disabilities
Research Reviews 9 (1): 40–47. doi:10.1002/mrdd.10056.
http://www3.interscience.wiley.com/cgi-bin/abstract/102531130/ABSTRACT. Retrieved 2006-
07-03. PMID 12587137
39.^ Olbrisch RR (1982). "Plastic surgical management of children with Down syndrome:
indications and results". British Journal of Plastic Surgery 35: 195–200. doi:10.1016/0007-
1226(82)90163-1.
40.^ Parens, E. (editor) (2006). Surgically Shaping Children : Technology, Ethics, and the Pursuit of
Normality. Baltimore: Johns Hopkins University Press. ISBN 0-8018-8305-9.
41.^ Klaiman, P and E Arndt (1989). "Facial reconstruction in Down syndrome: perceptions of the
results by parents and normal adolescents". Cleft Palate Journal 26: 186–190; discussion 190–
192. PMID 2527096. Also, see Arndt, EM, A Lefebvre, F Travis, and IR Munro (1986). "Fact
and fantasy: psychosocial consequences of facial surgery in 24 Down syndrome children". Br J
Plast Surg 4: 498–504. doi:10.1016/0007-1226(86)90120-7. PMID 2946342.
42.^ SA Pensler (1990). "The efficacy of tongue resection in treatment of symptomatic macroglossia
in the child". Ann Plast Surg 25: 14–17. doi:10.1097/00000637-199007000-00003. See also KM
Van Lierde, H Vermeersch, J Van Borsel, P Van Cauwenberge (2002/2003). "The impact of a
 partial glossectomy on articulation and speech intelligibility". Oto-Rhino-Laryngologia Nova 12:
305–310. doi:10.1159/000083122.
43.^ Leshin, L (2000). "Plastic Surgery in Children with Down Syndrome". http://www.ds-
health.com/psurg.htm. Retrieved 2006-07-25.
44.^ National Down Syndrome Society. "Position Statement on Cosmetic Surgery for Children with
Down Syndrome". http://www.ndss.org/content.cfm?fuseaction=InfoRes.HlthArticle&article=34.
Retrieved 2006-06-02.
45.^ For criticism of the method, see Novella, S. "Psychomotor Patterning".
http://www.quackwatch.org/01QuackeryRelatedTopics/patterning.html. Retrieved 2006-06-02.
46.^ Young, Emma (2002-03-22). "Down's syndrome lifespan doubles". New Scientist.
http://www.newscientist.com/article.ns?id=dn2073. Retrieved 2006-10-14.
47.^ Current Medical Dianosis & Treatment 1999 ed. Lawrence M. Tierney, Jr., MD, Stephen J.
McPhee, MD, Maxine A. Papadakis, MD, Appleton & Lange, 1999. pp.1546 ISBN 0-8385-1550-
9
48.^ Based on estimates by National Institute of Child Health & Human Development "Down
syndrome rates". Archived from the original on 2006-09-01.
http://web.archive.org/web/20060901004316/http://www.nichd.nih.gov/publications/pubs/downs
yndrome/down.htm#Questions. Retrieved 2006-06-21.
49.^ Center for Disease Control (6 January 2006). "Improved National Prevalence Estimates for 18
Selected Major Birth Defects, United States, 1999–2001". Morbidity and Mortality Weekly
Report 54 (51 & 52): 1301–1305.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5451a2.htm.
50.^ Huether, C.A. (1998). "Maternal age specific risk rate estimates for Down syndrome among
live births in whites and other races from Ohio and metropolitan Atlanta, 1970-1989". J Med
Genet 35(6): 482–490. doi:10.1136/jmg.35.6.482. PMCID: PMC1051343
51.^ Estimate from "National Down Syndrome Center".
http://www.ndsccenter.org/resources/package3.php. Retrieved 2006-04-21.
52.^ "Prevalence and Incidence of Down Syndrome". Diseases Center-Down Syndrome. Adviware
Pty Ltd.. 2008-02-04. http://www.wrongdiagnosis.com/d/down_syndrome/prevalence.htm.
Retrieved 2008-02-17. "incidence increases...especially when...the father is older than age 42"
53.^ Warner, Jennifer. "Dad's Age Raises Down Syndrome Risk, Too", "WebMD Medical News".
http://www.webmd.com/infertility-and-reproduction/news/20030701/dad-age-down-syndrome.
Retrieved 2007-09-29.
54.^ Down, J.L.H. (1866). "Observations on an ethnic classification of idiots". Clinical Lecture
Reports, London Hospital 3: 259–262. http://www.neonatology.org/classics/down.html.
Retrieved 2006-07-14. For a history of the disorder, see OC Ward (1998). John Langdon Down,
1828–1896. Royal Society of Medicine Press. ISBN 1-85315-374-5. or Conor, Ward. "John
Langdon Down and Down's syndrome (1828–1896)".
http://www.intellectualdisability.info/values/history_DS.htm. Retrieved 2006-06-02.
55.^ Conor, W.O. (1999). "John Langdon Down: The Man and the Message". Down Syndrome
Research and Practice 6 (1): 19–24. doi:10.3104/perspectives.94.
56.^ Warkany, J. (1971). Congenital Malformations. Chicago: Year Book Medical Publishers, Inc.
pp. 313–314. ISBN 0-8151-9098-0.
57.^ Lejeune J, Gautier M, Turpin R (1959). "Etude des chromosomes somatiques de neuf enfants
mongoliens". Comptes Rendus Hebd Seances Acad Sci 248 (11): 1721–1722.
http://gallica.bnf.fr/ark:/12148/bpt6k32002/f1759.chemindefer.
58.^ "Jérôme Lejeune Foundation".
http://www.fondationlejeune.org/eng/Content/Fondation/professeurlj.asp. Retrieved 2006-06-02.
59.^ Gordon, Allen; C.E. Benda, J.A. Böök, C.O. Carter, C.E. Ford, E.H.Y. Chu, E. Hanhart,
George Jervis, W. Langdon-Down, J. Lejeune, H. Nishimura, J. Oster, L.S. Penrose, P.E. Polani,
Edith L. Potter, Curt Stern, R. Turpin, J. Warkany, and Herman Yannet (1961). "Mongolism
(Correspondence)". The Lancet 1 (7180): 775.
60.^ Howard-Jones, Norman (1979). "On the diagnostic term "Down's disease"". Medical History 23
(1): 102–104. PMID 153994.
61.^ A planning meeting was held on 20 March 1974, resulting in a letter to The
Lancet."Classification and nomenclature of malformation (Discussion)". The Lancet 303 (7861):
798. 1974. doi:10.1016/S0140-6736(74)92858-X. PMID 4132724. The conference was held 10
February-11 February 1975, and reported to The Lancet shortly afterward."Classification and
nomenclature of morphological defects (Discussion)". The Lancet 305 (7905): 513. 1975.
doi:10.1016/S0140-6736(75)92847-0. PMID 46972.
62.^ Leshin, Len (2003). "What's in a name". http://www.ds-health.com/name.htm. Retrieved 2006-
05-12.
63.^ Inclusion. National Down Syndrome Society. http://www.ndss.org/index.php?
option=com_content&task=view&id=1941&Itemid=236. Retrieved 2006-05-21.
64.^ National Down Syndrome Society
65.^ Down Syndrome South Africa
66.^ Stephane Ginnsz. "Film Actor with Down Syndrome". ginnsz.com.
http://www.stephane.ginnsz.com/. Retrieved 2006-12-08.
67.^ Lomon, Chris (2003-02-28). "NHL Alumni RBC All-Star Awards Dinner". NHL Alumni.
http://www.nhlalumni.com/slam/hockey/nhlalumni/news/03/0228.html. Retrieved 2006-12-08.
68.^ "Pujols Family Foundation Home Page". http://www.pujolsfamilyfoundation.org/index2.html.
Retrieved 2006-12-08.
69.^ "Special Olympic Athlete Stars in Movie".
http://www.specialolympics.org/Special+Olympics+Public+Website/English/Press_Room/Global
_News_Archive/2004+Global+News+Archive/Special+Olympics+athlete+stars+in+movie.htm.
Retrieved 2007-11-05.
70.^ "Bratislava International Film festival 2004".
http://www.imdb.com/Sections/Awards/Bratislava_International_Film_Festival/2004. Retrieved
2007-11-05.
71.^ "Up Syndrome on the Internet Movie Database". http://us.imdb.com/title/tt0261375/. Retrieved
2009-04-19.
72.^ "Friends on Both Sides of Film".
http://www.caller2.com/2001/april/27/today/ricardob/24440.html. Retrieved 2001-04-27. from
the Corpus-Christi Caller Times
73.^ Online 'Mendelian Inheritance in Man' (OMIM) AMYLOID BETA A4 PRECURSOR
PROTEIN; APP -104760, gene located at 21q21. Retrieved on 2006-12-05.
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75.^ a b Online 'Mendelian Inheritance in Man' (OMIM) V-ETS AVIAN ERYTHROBLASTOSIS
VIRUS E26 ONCOGENE HOMOLOG 2; ETS2 -164740, located at 21 q22.3. Retrieved on
2006-12-05.
 76.^ Ellis JM, Tan HK, Gilbert RE, et al. (2008). "Supplementation with antioxidants and folinic
acid for children with Down's syndrome: randomised controlled trial". BMJ 336 (7644): 594–7.
doi:10.1136/bmj.39465.544028.AE. PMID 18296460.

References
Research bibliography
• Arron JR, Winslow MM, Polleri A, et al. (2006). "NFAT dysregulation by increased
dosage of DSCR1 and DYRK1A on chromosome 21". Nature 441 (7093): 595–600.
doi:10.1038/nature04678. PMID 16554754.
• Epstein CJ (June 2006). "Down's syndrome: critical genes in a critical region". Nature
441 (7093): 582–3. doi:10.1038/441582a. PMID 16738647.
• Ganong, W.J. (2005). Review of Medical Physiology (21st ed.). New York: Mc-Graw
Hill. ISBN 0071402365.
• Nelson DL, Gibbs RA (2004). "Genetics. The critical region in trisomy 21". Science
(journal) 306 (5696): 619–21. doi:10.1126/science.1105226. PMID 15499000.
• Olson LE, Richtsmeier JT, Leszl J, Reeves RH (2004). "A chromosome 21 critical region
does not cause specific Down syndrome phenotypes". Science (journal) 306 (5696): 687–
90. doi:10.1126/science.1098992. PMID 15499018.
• Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human
chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
• Underwood, J.C.E. (2004). General and Systematic Pathology (4th ed.). Edinburgh:
Churchill Livingstone. ISBN 0443073341.
General bibliography
• Beck, M.N. (1999). Expecting Adam. New York: Berkley Books.
• Buckley, S. (2000). Living with Down Syndrome. Portsmouth, UK: The Down Syndrome
Educational Trust. ISBN 1903806011. http://books.google.com/books?
id=__5wB08U2hMC.
• Down Syndrome Research Foundation (2005). Bright Beginnings: A Guide for New
Parents. Buckinghamshire, UK: Down Syndrome Research Foundation.
http://www.dsrf.co.uk/Reading_material/Bright_beginnings.htm.
• Dykens EM (2007). "Psychiatric and behavioral disorders in persons with Down
syndrome". Ment Retard Dev Disabil Res Rev 13 (3): 272–8. doi:10.1002/mrdd.20159.
PMID 17910080.
• Hassold, T.J., D. Patterson, eds. (1999). Down Syndrome: A Promising Future, Together.
New York: Wiley Liss.
• Kingsley, J.; M. Levitz (1994). Count Us In: Growing up with Down Syndrome. San
Diego: Harcourt Brace.
• Pueschel, S.M., M. Sustrova, eds. (1997). Adolescents with Down Syndrome: Toward a
More Fulfilling Life. Baltimore, MD: Paul H. Brookes.
• Selikowitz, M. (1997). Down Syndrome: The Facts (2nd ed.). Oxford, UK: Oxford
University Press. ISBN 0192626620.
 • Van Dyke, D.C.; P.J. Mattheis, S. Schoon Eberly, J. Williams (1995). Medical and
Surgical Care for Children with Down Syndrome. Bethesda, MD: Woodbine House.
ISBN 0933149549.
• Zuckoff, M. (2002). Choosing Naia: A Family's Journey. New York: Beacon Press.
ISBN 0807028177.
External links

Wikimedia Commons has media related to: Down syndrome

• Down syndrome complications, frequent symptoms and details

• Facts about Down Syndrome from the National Institutes of Health

[hide]
v•d•e
Pathology: chromosome abnormalities (Q90-Q99 · 758)

Down syndrome (21) · Edwards syndrome

(18) · Patau syndrome (13)
Trisomies
Trisomy 9 · Warkany syndrome 2 (8) · Trisomy
22/Cat eye syndrome (22) · Trisomy 16

Wolf-Hirschhorn syndrome (4) · Cri du

Autosomal
chat/Chromosome 5q deletion syndrome (5) ·
Williams syndrome (7) · Jacobsen syndrome
Monosomies/deletion
(11) · Miller-Dieker syndrome/Smith-Magenis
s
syndrome (17) · Di George's syndrome (22)
genomic imprinting (Angelman
syndrome/Prader-Willi syndrome (15))

MonosomyTurner syndrome (XO)

Klinefelter's syndrome (47,XXY) ·

48,XXYY · 48,XXXY · 49,XXXYY ·
49,XXXXY
X/Y linked Trisomy/tetrasomy,
otherTriple X syndrome (47,XXX) · 48,XXXX ·
karyotypes/mosaics49,XXXXX
47,XYY · 48,XYYY · 49,XYYYY
46,XX/XY

Translocations Leukemia/lymphomLymphoidBurkitt's lymphoma t(8 MYC;14

a IGH) · Follicular lymphoma t(14
IGH;18 BCL2) · Mantle cell
 lymphoma/Multiple myeloma t(11
CCND1:14 IGH) · Anaplastic large
cell lymphoma t(2 ALK;5 NPM1) ·
Acute lymphoblastic leukemia

Philadelphia chromosome t(9 ABL;

22 BCR) · Acute myeloblastic
leukemia with maturation t(8
RUNX1T1;21 RUNX1) · Acute
Myeloid
promyelocytic leukemia t(15
PML,17 RARA) · Acute
megakaryoblastic leukemia t(1
RBM15;22 MKL1)

Ewing's sarcoma t(11 FLI1; 22 EWS) ·

Synovial sarcoma t(x SYT;18 SSX) ·
Dermatofibrosarcoma protuberans t(17
COL1A1;22 PDGFB) · Myxoid liposarcoma
Other
t(12 DDIT3; 16 FUS) · Desmoplastic small
round cell tumor t(11 WT1; 22 EWS) · Alveolar
rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1
PAX7; 13 FOXO1)

Gonadal
Mixed gonadal dysgenesis · XX gonadal dysgenesis
dysgenesis

Other Fragile X syndrome · Uniparental disomy

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