1. Introduction
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
1

2. 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]
2

3. Chapter 1
Characteristics
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,
3

4. 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
4

5. 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]
5

6. Chapter 1.1
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
6

7. 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
7

8. 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]
8

9. Chapter 1.2
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]
9

10. Chapter 2
Genetics
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]
10

11. Karyotype for trisomy Down syndrome. Notice the three
copies of chromosome 21
11

12. Chapter 2.1
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]
Chapter 2.2
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
12

13. 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]
Chapter 2.3
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
13

14. 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.
Chapter 2.4
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.
14

15. Chapter 3
Screening
15

16. 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
16

17. 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
17

18. 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
translucency/free ultrasound
beta/PAPPA screen to measure
(aka "1st Nuchal
Trimester Translucency
18

19. Combined Test") in addition
to the
freeBeta hCG
and PAPPA
(pregnancy-
associated
plasma
protein 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
19

20. there is
operator
error,
resulting in
a lower-
than-
advertised
sensitivity
and higher
false-
positive
rate,
possibly in
the 5-10%
range.
Integrated Test 10-13.5 95%[29] 5% The
and 15–20 Integrated
test uses
measurements
from both
the 1st
Trimester
Combined
test and the
2nd
trimester
Quad test to
yield a more
accurate
20

21. screening
result.
Because all
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
21

22. 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]
Chapter 3.1
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
22

23. "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]
Chapter 4
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.
23

24. Chapter 4.1
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."
24

25. Chapter 4.2
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.
Chapter 5
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
25

26. 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]
Chapter 6
Epidemiology
Graph showing probability of Down syndrome as a
function of maternal age.
26

27. 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.
27

28. Chapter 7
History
28

29. 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 1970s.
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
29

30. 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
30

31. among professionals in the USA, Canada and other
countries; Down's syndrome is still used in the United
Kingdom and other areas.[62]
Chapter 8
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,
31

32. 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
32

33. 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.
Chapter 8.1
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.
33

34. • 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
34

35. • 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
Chapter 9
Research
Down syndrome is “a developmental abnormality
characterized by trisomy of human chromosome 21" (Nelson
35

36. 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
36

37. 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
37

38. 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]
38

39. Footnotes
39

40. 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&res
num=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–
40

41. 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.
41

42. 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#TheOccur
rence. 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/hw167
989. 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
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43. 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
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"Determinants of parental decisions after the prenatal diagnosis of
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33. ^ Peter Horrocks (2008-12-05). "Changing attitudes?". BBC News.
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.
34. ^ Glover, NM and Glover, SJ (1996). "Ethical and legal issues
regarding selective abortion of fetuses with Down syndrome". Ment.
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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
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37. ^ New Eugenics and the newborn: The historical "cousinage" of
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38. ^ Erik Parens and Adrienne Asch (2003). "Disability rights critique
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39. ^ Olbrisch RR (1982). "Plastic surgical management of children with
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44. 40. ^ Parens, E. (editor) (2006). Surgically Shaping Children :
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45. ^ For criticism of the method, see Novella, S. "Psychomotor
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48. References
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48

49. 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.
49