When we talk about genetic disease, the first thing that come in our mind is "Down Syndrome". Down syndrome: is a genetic disease that comes from a meiotic nondisjunction in the DNA of the divided cell, so cause a three chromosomes in the Number (21). Down syndrome is continuous with the life of person, and the patient needs a special care from his society, family, and even his country. In this report, I will discuss everything about "Down Syndrome", causes, symptoms, diagnosis and even treatment. I will also mention some samples of people with Down syndrome who did interesting things in our world. The maternal age is one of the most common cause of Down Syndrome, sometimes the radiation causes this syndrome or increase its risk. No treatment is known for Down Syndrome, but they can be rehabilitated for life. Finally, I hope you enjoy and take benefit from this report, and know everything about this common disease which is very difficult to get along with normal people

1. DOWN SYNDROME
UNIVERSITY OF BAGHDAD
COLLEGE OF MEDICINE
Done by The Student:
Hashim Talib Hashim
H.T.H
"Genetic Basis of Medicine Module"

2. 1
CONTENTS
1.Introduction ……………………………………...…… 2
2.Search board and Discussion:
 What's "Down Syndrome"? …………………… 3
 History of down syndrome ……………...…….. 8
 Epidemiology and prognosis of DS ............. 10
 Clinical symptoms …………………………….. 12
 Pathogenesis ...………………………………… 19
 Diagnosis ……………………………………….. 21
 Treatment ...…………………………………….. 24
 Famous People with Down Syndrome ….…. 28
3.Summary …………………………………………….. 32
4.How to identify Down Syndrome? ………………. 33
5.References …..……………………………………… 34

3. 2
Introduction
When we talk about genetic disease, the first thing that come in our
mind is "Down Syndrome".
Down syndrome: is a genetic disease that comes from a meiotic
nondisjunction in the DNA of the divided cell, so cause a three
chromosomes in the Number (21).
Down syndrome is continuous with the life of person, and the patient
needs a special care from his society, family, and even his country.
In this report, I will discuss everything about "Down Syndrome",
causes, symptoms, diagnosis and even treatment. I will also mention
some samples of people with Down syndrome who did interesting things
in our world.
The maternal age is one of the most common cause of Down
Syndrome, sometimes the radiation causes this syndrome or increase
its risk.
No treatment is known for Down Syndrome, but they can be rehabilitated
for life.
Finally, I hope you enjoy and take benefit from this report, and know
everything about this common disease which is very difficult to get
along with normal people.

4. 3
What is …
DOWN SYNDROME
The human body is made of cells; all cells contain a center, called a
nucleus, in which genetic material is stored. This genetic material, known
as genes, carries the codes responsible for all our inherited characteristics
and are grouped along rod-like structures called chromosomes (see figure
below). Typically, the nucleus of each cell contains 23 pairs of
chromosomes, half of which are inherited from each parent. Down
syndrome occurs when an individual has a full or partial extra copy of
chromosome 21.
This additional genetic material alters the course of development and causes
the characteristics associated with Down syndrome. A few of the common
physical traits of Down syndrome are low muscle tone, small stature, an
upward slant to the eyes, and a single deep crease across the center of the
palm - although each person with Down syndrome is a unique individual
and may possess these characteristics to different degrees, or not at all]1[
.

5. 4
Trisomy 21 (Down syndrome)]2[
, the most common numerical
abnormality resulting in birth defects (intellectual disability, abnormal
facies, heart malformations), is usually caused by nondisjunction in the
mother and occurs most frequently in children born to women older than
35 years of age, reflecting the fact that the risk of meiotic nondisjunction
increases with increasing maternal age. Other trisomies that result in
syndromes of abnormal development involve chromosomes 8, 9, 13, and 18.
Monosomies involving autosomal chromosomes are fatal, but monosomy of
the X chromosome (Turner syndrome) is compatible with life. This
condition is usually (80%) a result
of nondisjunction during meiosis
of paternal chromosomes and is
characterized by infertility, short
stature, webbing of the neck, and
other defects (see Fig:1).
Karyotyping of embryonic cells
obtained by amniocentesis or
chorionic villus biopsy can detect
chromosome abnormalities
prenatally.
Chromosomes sometimes break,
and the pieces may create partial
monosomies or trisomies or
become attached (translocated) to
other chromosomes. Translocation of part of chromosome 21 onto
chromosome 14, for example, accounts for approximately 4% of cases of
Down syndrome.
Chromosomes may also be altered by mutations in single genes. The risk of
chromosomal abnormalities is increased by maternal and paternal age over
35 years.
Down syndrome ]3[
is a set of physical and mental traits are resulted from
a gene problem which happens before birth. Children who have Down
syndrome tend to have many features, such as a flat face and a short neck.
They also have a degree of intellectual disability. This varies from person to
another. But in most cases it is mild to moderate.
In individuals with Down syndrome, however, the cells usually contain
47, not 46, chromosomes; the extra chromosome is the 21st. This excess
Fig:1

6. 5
genetic material, in the form of additional genes along chromosome 21,
results in Down syndrome.
The extra 21st chromosome is detected by using a procedure called a
karyotype]4[
(see the fig:2 below). A karyotype is a visual display of the
chromosomes grouped by size, number and shape. Chromosomes may be
studied by examining blood or tissue cells. Individual chromosomes are
identified, stained and numbered from largest to smallest. Ninety-five
percent of occurrences of Down syndrome result from the presence of an
extra (third) chromosome, a condition described as Trisomy 21.
Those who have a child with Down syndrome, have about a 1% risk of
having a second child with the same thing, if both parents are found to have
normal karyotypes [5]
.
The extra chromosome 21 material may also occur due to a Robertsonian
translocation in 2–4% of cases. In this case, the long arm of chromosome 21
is attached to another chromosome, often chromosome 14. In a male
affected by Down syndrome, it results in a karyotype of 46XY, t(14q21q).
This may be a new mutation or previously present in one of the parents. The
parent with such a translocation is usually normal physically and mentally;
Fig:2

7. 6
however, during production of egg or sperm cells, a higher chance of
building reproductive cells with extra chromosome 21 material exists. This
results in a 15% chance of having a child with Down syndrome when the
mother is affected but a less than 5% probability if the father is affected.
The probability of this type of Down syndrome is not related to the age of
the mother. Some children without Down syndrome may inherit the
translocation and have a higher probability of having children of their own
with Down syndrome. In this case it is sometimes known as "familial Down
syndrome"]6[
.
The extra genetic material present in Down Syndrome results in
overexpression of a portion of the 310 genes located on chromosome 21. This
overexpression has been estimated at around 50%. Some research has
suggested that Down syndrome critical region is located at bands 21q22.1–
q22.3, with this area including genes for amyloid, superoxide dismutase, and
likely the ETS2 proto oncogene. Other research, however, has not
confirmed these findings. microRNAs are also proposed to be involved.
The dementia which occurs in Down syndrome is caused by an excess of
amyloid beta peptide that's produced in the brain and is similar to
Alzheimer's disease. This peptide is processed from amyloid precursor
protein, the gene for which is located on chromosome 21. Senile plaques and
neurofibrillary tangles are present in nearly all by 35 years of age, though
dementia may not be present. Those with Down Syndrome also lack a
normal number of lymphocytes and produce less antibodies which
contributes to their increased risk of infection in their bodies]7[
.
Down syndrome is associated with an increased risk of many chronic
diseases which are typically associated with older age such as Alzheimer's
disease as mentioned above. The accelerated aging suggests that trisomy 21
increases the biological age of tissues, but molecular evidence for this
hypothesis is sparse. According to a biomarker of tissue age known as
epigenetic clock, trisomy 21 increases the age of blood and brain tissue (on
average by 6.6 years)]8[
.
There are three types of Down Syndrome, which are]9[
(see Fig:3):
1- Trisomy (nondisjunction)
2- Translocation Down syndrome
3- Mosaicism.

8. 7
1-TRISOMY 21 (NONDISJUNCTION)
Down syndrome is usually caused by an error in cell division called
"nondisjunction" which is mentioned previously. Nondisjunction results in
an embryo with three copies of chromosome 21 instead of the usual two.
Prior to or at conception, a pair of 21st chromosomes in either the sperm or
the egg fails to separate. As the embryo develops, the extra chromosome is
replicated in every cell of the body. This type of Down syndrome, which
accounts for 95% of cases, is called trisomy 21.
2-MOSAICISM
Mosaicism (or mosaic Down syndrome) is diagnosed when there is a
mixture of two types of cells, some containing the usual 46 chromosomes
and some containing 47. Those cells with 47 chromosomes contain an extra
chromosome 21.
Mosaicism is the least common form of Down syndrome and accounts for
only about 1% of all cases of Down syndrome. Research has indicated that
individuals with mosaic Down syndrome may have fewer characteristics of
Down syndrome than those with other types of Down syndrome. However,
broad generalizations are not possible due to the wide range of abilities
people with Down syndrome possess.
3- TRANSLOCATION
In translocation, which accounts for about 4% of cases of Down
syndrome, the total number of chromosomes in the cells remains 46;
however, an additional full or partial copy of chromosome 21 attaches to
another chromosome, usually chromosome 14. The presence of the extra
full or partial chromosome 21 causes the characteristics of Down syndrome.
Fig:3

9. 8
History of down syndrome
Down syndrome was first described by Dr.
John Langdon Down (who appears in the photo
on the side) in 1866. While working in London
in 1866, he noticed that some of his patients,
though not related, had similar physical
characteristics that created their condition
different from other types of intellectual
disabilities. Langdon Down thought that their
facial features resembled those of the
Mongolian people and so, he introduced the
term Mongol. People with Down syndrome were
once referred to as having “Mongolism” or
being “Mongols”. These terms are
inappropriate and are no longer used when
referring to a person with Down syndrome]10[
.
It was not until 1959 that Dr. Jerome Lejeune (the photo in the bottom), a
French physician, made the discovery that Down syndrome was the result
of a chromosomal anomaly. His research led him to the fact that the cells of
people with Down syndrome had 47 chromosomes, compared to the typical
46 chromosomes. Shortly after, it was discovered that chromosome number
21 contained an extra partial or complete chromosome, thus the term
Trisomy 21 was born.
In antiquity, a lot of infants with disabilities were
either killed or abandoned. A number of historical
pieces of art are believed to portray Down syndrome,
including pottery from AD 500 from South America
and the 16th-century painting The Adoration of the
Christ Child]11[
.
In the 20th
century, many 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

10. 9
several countries began programs of forced sterilization of individuals with
Down syndrome and comparable degrees of disability. Action T4 in Nazi
Germany made public policy of a program of systematic involuntary
Euthanization [12]
.
With the discovery of karyotype techniques in the 1950s, it became
possible to identify abnormalities of chromosomal number or shape.
In 1959, Jérôme Lejeune reported the discovery that Down syndrome
resulted from an extra chromosome. However, Lejeune's claim to the
discovery has been disputed, and in 2014, the Scientific Council of the
French Federation of Human Genetics unanimously awarded its Grand
Prize to his colleague Marthe Gautier for her role in this discovery. The
discovery was in the laboratory of Raymond Turpin at the Hôpital
Trousseau in Paris, France. Jérôme Lejeune and Marthe Gautier were both
his students [13]
As a result, the condition became known as trisomy 21. Even before the
discovery of its causes, the presence of the syndrome in all races, its
association with older maternal age, and its rarity of recurrence had been
noticed. Medical texts had assumed it was caused by a combination of
inheritable factors that had not been identified. Other theories had focused
on injuries sustained during birth [14]
.
Children with "hereditary defects" such as Down syndrome were among the first victims of the Nazi
euthanasia program, which killed those deemed "unworthy of life."

11. 10
Epidemiology and prognosis
of "Down Syndrome"
Prognosis (see Fig:4):
Between 5% and 15% of children with Down syndrome in Sweden attend
regular school. Some graduate from high school; moreover, most do not.
Of those with intellectual disability in the United States who attended high
school about 40% graduated. Many learn to read and write and some are
able to do paid work. In adulthood about 20% in the United States do paid
work in some capacity. In Sweden, however, less than 1% have regular jobs.
Many are able to live semi-independently, but they often require help with
financial, medical, and legal matters. Those with mosaic Down syndrome
usually have better outcomes [15]
.
Individuals with Down syndrome have a higher risk of early death than
the general population. This is most often from heart problems or
infections. Following improved medical care, particularly for heart and
gastrointestinal problems, the life expectancy has increased. This increase
has been from 12 years in 1912s, to 25 years in the 1980s, to 50 to 60 years
in the developed world in the 2000s. Currently between 4 and 12% die in
the first year of life. The probability of long-term survival is partly
determined by the presence of heart problems. In those with congenital
heart problems 60% survive to 10 years and 50% survive to 30 years of age.
In those without heart problems 85% survive to 10 years while 80% survive
to 30 years of age. About 10% live to 70 years of age. The National Down
Syndrome Society have developed information regarding the positive
aspects of life with Down syndrome [16]
.
Deaths due to Down syndrome per million persons in 2012
0-0 1-1 2-2 3-3 4-4 5-5 6-6 7-8 9-16
Fig: 4

12. 11
Epidemiology (see Fig:5):
Globally, as of 2010, Down syndrome occurs in about 1 per 1000 births
and results in about 17,000 deaths. More children are born with Down
syndrome in countries where abortion is not allowed and in countries where
pregnancy more commonly occurs at a later age. About 1.4 per 1000 live
births in the United States and 1.1 per 1000 live births in Norway are
affected. In the 1950s, in the United States, it happened in 2 per 1000 live
births with the decrease since then due to prenatal screening and abortions.
The number of pregnancies with Down syndrome is more than two times
greater with many spontaneously aborting. It is the cause of 8% of all
congenital disorders [17]
.
Maternal age affects the chances of having a pregnancy with Down
syndrome.
The estimated maternal age-adjusted prevalence of DS based on the
surveillance of ~22% of the live births in the U.S. was 13.65 [95%
confidence intervals (CI): 13.22–14.09] per 10,000 live births, or 1/732. This
suggests that ~ 5,400 of the ~ 4 million infants born each year in the U.S.
have DS ]18[
.
At age 20, the chance is one in 1441; at age 30, it is one in 959; at age 40,
it is one in 84; and at age 50 it is one in 44. Although the probability increases
with maternal age as mentioned above, 70% of children with Down
syndrome are born to women 35 years of age and younger, because younger
people have more children. The father's older age is also a risk factor in
women older than 35, but not in women younger than 35, and may partly
explain the increase in risk as women age [19]
.
The risk of having a Down
syndrome pregnancy in relation
to a mother's age [20]
Figure: 5

13. 12
Signs AND Symptoms
The patients with Down syndrome are likely to appear as (8 – 9) years
child with their behavior, thinking, talking and even their mental function.
They cannot talk properly, they cannot eat or walk properly too, and they
do things that children do them (see Table:1).
They also typically have a poor immune function and generally reach
developmental milestones at a later age. They have an increased risk of a
number of other health problems, including congenital heart defect,
epilepsy, leukemia, thyroid diseases, and mental disorders, among others.
Condition %
Hearing loss 75
Vision problem 60
Cataracts 15
Refractive error 50
Obstructive sleep apnea 50 – 75
Otitis media 50 – 70
Congenital heart disease 40 – 50
Hypodontia and delayed dental eruption 23
Gastrointestinal atresias 12
Thyroid disease 14 – 18
Seizures 1 – 13
Hematologic problems
Anemia 3
Iron deficiency 10
Transient myeloproliferative disorder 10
Leukemia 1
Celiac disease 5
Atlantoaxial instability 1 – 2
Autism 1
Hirschsprung disease >1
Table 1: Medical Problems Common in Down Syndrome]21[

14. 13
There are many types of symptom and signs which are related to Down
Syndrome, and we can recognize it by them (see Fig:6 below).
These symptoms include the following (see Table:2):
1) Physical
2) Neurological
3) Cancer
4) Endocrine
5) Fertility
6) Heart
7) Gastrointestinal
8) Senses
9) Teeth
Characteristics % Characteristics %
Mental impairment 99% Abnormal teeth 60%
Stunted growth 90% Slanted eyes 60%
Umbilical hernia 90% Shortened hands 60%
Increased skin back of neck 80% Short neck 60%
Low muscle tone 80% Obstructive sleep apnea 60%
Narrow roof of mouth 76% Bent fifth finger tip 57%
Flat head 75% Brush field spots in the iris 56%
Flexible ligaments 75% Single transverse palmar crease 53%
Proportionally large tongue 75% Protruding tongue 47%
Abnormal outer ears 70% Congenital heart disease 40%
Flattened nose 68% Strabismus 35%
Separation of 1st
and 2nd
toes 68% Undescended testicles 20%
Table 2: The clinical symptoms of Down syndrome and its risk factors ]22[
Fig: 6

15. 14
1.Physical:-
People with Down syndrome may have some or all of these physical
characteristics: a small chin, slanted
eyes, poor muscle tone, a flat nasal
bridge, a single crease of the palm,
and a protruding tongue caused by a
small mouth and relatively large
tongue. These airway's changes lead
to obstructive sleep apnea in around
half of those with Down syndrome.
Other common features include: a flat
and wide face, a short neck, excessive
joint flexibility, extra space between
big toe and 2nd
toe, abnormal patterns
on the fingertips and short fingers.
Instability of the atlantoaxial joint
occurs in about 20% and may lead to
spinal cord injury in 1–2%. Hip
dislocations may occur without
trauma in up to a third of people with
Down syndrome.
Growth in height is slower, resulting in adults who tend to have short
stature—the average height for men is 154 cm and for women is 142 cm.
Individuals with Down syndrome are at increased risk for obesity as they
grow ]23[
(as in Figure:7).
2. Neurological:-
Most individuals with Down syndrome have mild (IQ: 50–69) or moderate
(IQ: 35–50) intellectual disability with some cases having severe (IQ: 20–35)
difficulties. Those with mosaic Down syndrome typically have IQ scores 10–
30 points higher. As they age, people with Down syndrome typically
perform less well than their same-age peers. Some after 30 years of age may
lose their ability to speak. This syndrome causes about a third of cases of
intellectual disability. Many developmental milestones are delayed with the
ability to crawl typically occurring around 8 months rather than 5 months
and the ability to walk independently typically occurring around 21 months
rather than 14 months.
Fig: 7

16. 15
Commonly, individuals with Down syndrome have better language
understanding than ability to speak. Between 10 and 45% have either a
stutter or rapid and irregular speech, making it difficult to understand
them. They typically do fairly well with social skills. Behavior problems are
not generally as great an issue as in other syndromes associated with
intellectual disability. In children with Down syndrome, mental illness
occurs in nearly 30% with autism occurring in 5–10%. People with Down
syndrome experience a wide range of emotions. While people with Down
syndrome are generally happy, symptoms of depression and anxiety may
develop in early adulthood.
Children and adults with Down syndrome are at increased risk of epileptic
seizures, which occur in 5–10% of children and up to 50% of adults. This
includes an increased risk of a specific type of seizure called infantile
spasms. Many (15%) who live 40 years or longer develop Alzheimer disease.
In those who reach 60 years of age, 50–70% have the disease [24]
.
3.Senses:-
Brush field spots (Fig:8), visible in the irises of a baby with Down
syndrome. Hearing and vision disorders occur in more than half of people
with Down syndrome. Vision problems occur in 38 to 80%. Between 20 and
50% have strabismus, in which the two eyes do not move together.
Cataracts (cloudiness of the lens of the eye) occur in 15%, and may be
present at birth. Keratoconus (a thin, cone-shaped cornea) and glaucoma
(increased eye pressure) are also more common, as are refractive errors
requiring glasses or contacts. Brush field spots (small white or
grayish/brown spots on the outer part of the iris) are present in 38 to 85%
of individuals.
Hearing problems are found in 50–90% of children with Down syndrome.
This is often the result of otitis media with effusion which occurs in 50–70%
and chronic ear infections which occur in 40 to 60%. ]25[
.
Fig 8: Brush field spots, visible in the irises of a baby with Down syndrome

17. 16
4.Heart:-
The rate of congenital heart disease
in newborns with Down syndrome is
around 40%. Of those with heart
disease, about 80% have an
atrioventricular septal defect or
ventricular septal defect with the
former being more common. Mitral
valve problems become common as
people age, even in those without
heart problems at birth. Other
problems that may occur include tetralogy of Fallot (Fig:10) and patent
ductus arteriosus (Fig:9). People with Down syndrome have a lower risk of
hardening of the arteries [24]
.
5. Cancer
Although the overall risk of cancer is not changed, the risk of leukemia
and testicular cancer is increased and risk of solid cancers is reduced. Solid
Fig:10
0
Fig:9

18. 17
cancers are believed to be less common due to
increased expression of tumor suppressor genes
present on chromosome 21.
Cancers of the blood are 10 to 15 times more
common in children with Down syndrome. In
particular, acute lymphoblastic leukemia is 20 times
more common and the Megakaryoblastic form of
acute myeloid leukemia (Fig:11) is 500 times more
common. Transient myeloproliferative disease, a
disorder of blood cell production that does not occur
outside of Down syndrome, affects 3–10% of infants.
The disorder is typically not serious but occasionally can be. It resolves most
times without treatment; however, in those who have had it, a 20 to 30%
risk of developing acute lymphoblastic leukemia at a later time exists [26]
.
6. Endocrine:-
Problems of the thyroid gland occur in 20–50% of individuals with Down
syndrome. Low thyroid is the most common form, occurring in almost half
of all individuals. Thyroid problems can be due to a poorly or
nonfunctioning thyroid at birth (known as congenital hypothyroidism)
which occurs in 1% or can develop later due to an attack on the thyroid by
the immune system resulting in Graves' disease or autoimmune
hypothyroidism. Type 1 diabetes mellitus is also more common ]27[
.
7.Gastrointestinal:-
Constipation occurs in nearly half of people with Down syndrome and
may result in changes in behavior. One potential cause is Hirschsprung
disease (Fig:12 & 13), occurring in 2–15%, which is
due to a lack of nerve cells controlling the colon ]28[
.
Other frequent congenital
problems include duodenal
atresia, pyloric stenosis,
Meckel diverticulum, and
imperforate anus. Celiac
disease affects about 7–
20% and gastroesophageal
reflux disease is also more
common [28]
.
Fig: 11
Fig: 12Fig: 13

19. 18
8.Teeth:-
Individuals with Down syndrome tend to be
more susceptible to gingivitis as well as early,
severe periodontal disease, necrotizing
ulcerative gingivitis, and early tooth loss,
especially in the lower front teeth. While
plaque and poor oral hygiene are contributing
factors, the severity of these periodontal disease
cannot be explained solely by external factors.
Research suggests that the severity is likely a
result of a weakened immune system. The
weakened immune system also contributes to
increased incidence of yeast infections in the
mouth (from Candida albicans).
Individuals with Down syndrome also tend to
have a more alkaline saliva resulting in a
greater resistance to tooth decay, despite
decreased quantities of saliva, less effective oral
hygiene habits and higher plaque indexes [29]
.
Higher rates of tooth wear and bruxism are also common. Other common
oral manifestations of Down syndrome include enlarged hypotonic tongue,
crusted and hypotonic lips, mouth breathing, narrow palate with crowded
teeth, class III malocclusion with an underdeveloped maxilla and posterior
crossbite, delayed exfoliation of baby teeth and delayed eruption of adult
teeth, shorter roots on teeth, and often missing and malformed (usually
smaller) teeth [30]
. Less common manifestations include cleft lip and palate,
enamel hypocalcification (20% prevalence) see Figure:14.
9. Fertility:-
Males with Down syndrome usually do not father children, while females
have lower rates of fertility relative to those who are unaffected. Fertility is
estimated to be present in 30–50% of females. Menopause typically occurs
at an earlier age. The poor fertility in males is thought to be due to problems
with sperm development; however, it may also be related to not being
sexually active. syndrome [31]
.
Fig: 14

20. 19
Pathogenesis
The duplication of a specific region of chromosome 21 could be
respotisible for the main features of Down syndrome. To define and localize
this region, we analyzed at the molecular level the DNA of two patients with
partial duplication of chromosome 21. These patients belong to two groups
of Down syndrome patients characterized by different partial trisomies 21:
1. duplication of the long arm, proximal to 21q22.2,
2. duplication of the end of the chromosome, distal to 21q22.2
They (The researchers) assessed the copy number of five chromosomes 21
sequences (SOD, D21S17, D21S55, ETS2, and D21SI5) and found that
D21S55 was duplicated in both cases. By means of pulsed-field gel analysis
and with the knowledge of regional mapping of the probes D21S17, D21S55
and ETS2, we estimated the size of the common duplicated region to be
between 400 and 3000 kilobases. This region, localized on the proximal part
of 21q22.3, is suspected to contain genes the overexpression of which is
crucial in the pathogenesis of Down syndrome ]32[
.
After review of all the published observations of partial trisomies 21, it was
concluded that a duplication of a small fraction of 21q22, adjacent to the
sub-band 21q22.2, could be of importance in the expression of Down
syndrome (Fig:15) ]32[
.
Fig: 15

21. 20
Study of clinical scores in Down syndrome patients, such as Jackson's
index, reveals that the phenotypic expression of trisomy 21 is variable from
one individual to another. The same heterogeneity is observed when
considering the intensity of mental deficiency.
Molecular analysis reveals that the 21q22.1-q22.3 regions, also known as
the Down syndrome critical region (DSCR), appears to contain the gene or
genes responsible for the congenital heart disease observed in Down
syndrome. A new gene, DSCR1, identified in region 21q22.1-q22.2, is highly
expressed in the brain and the heart and is a candidate for involvement in
the pathogenesis of Down syndrome, particularly with regard to intellectual
disability and cardiac defects ]33[
.
See figure (16) on the side which is taken
from the research of (Critical role of the
D21S55 region on chromosome 21 in the
pathogenesis of Down syndrome)]32[
a) Schematic representation of the
quantification of five chromosomes 21
sequences in the two patients. At left is
the genetic linkage map for SOD],
D21S17, D21S15 (9), D21S55 (P.C.W.,
unpublished data), and ETS2 (10);
cM, centimorgans. At right is the
sequence copy number on the
rearranged chromosome 21 of FG and
of IG (small bar means one copy and
large bar means two copies).
b) Regional mapping of the chromosome
21 sequences (11-15, 27).
Fig: 16

22. 21
Diagnosis
Down syndrome can be diagnosed in two stages of life of the patient, which
are:
1- Prenatally.
2- After birth.
The American College of Obstetricians and Gynecologists recommends
offering the option of screening tests and diagnostic tests for Down
syndrome to all pregnant women, regardless of age ]34[
, these tests are done
prenatally and they are:
 Screening tests: can indicate the likelihood or chances that a mother is
carrying a baby with Down syndrome. But these tests can't tell for sure
or diagnose whether the baby has Down syndrome.
 Diagnostic tests: can identify or diagnose whether your baby has Down
syndrome.
We can get the testes above by some medical ways as we explain here:
1-Screening Tests:-
At this time the most commonly used screening
test is “The Triple Screen.” This is a combination
of three tests that measure quantities of different
substances in the blood. These tests are usually
done between 15 and 20 weeks of gestation.
Sonograms (ultrasounds) are usually
performed in conjunction with other screenings.
These can show some physical traits that are
helpful in calculating the risk of Down syndrome (Fig:17).
Screening tests do not accurately confirm the diagnosis of Down syndrome.
In fact, false positives and false negatives frequently occur ]35[
.
Fig: 17

23. 22
2-Diagnostic Tests:-
Three diagnostic tests are currently available ]35[
:
 Chorionic villus sampling (CVS). In CVS (Fig:19), cells are taken from
the placenta and used to analyze the fetal chromosomes. This test is
typically performed in the first trimester, between 10 and 13 weeks of
pregnancy. The risk of pregnancy loss (miscarriage) from a CVS is
very low.
 Amniocentesis (Fig:18). A sample of the amniotic fluid surrounding
the fetus is withdrawn through a needle inserted into the mother's
uterus. This sample is then used to analyze the chromosomes of the
fetus. Doctors usually perform this test in the second trimester, after
15 weeks of pregnancy. This test also carries a very low risk of
miscarriage.
 Percutaneous Umbilical Blood Sampling (PUBS) is performed after 20
weeks.
Fig: 18
Fig: 19

24. 23
Now we will discuss the diagnosis ways after birth. Down Syndrome is
usually identified at birth by the presence of certain physical traits: low
muscle tone, a single deep crease across the palm of the hand, a slightly
flattened facial profile and an upward slant to the eyes. Because these
features may be present in babies without Down syndrome, a chromosomal
analysis called a karyotype is done to confirm the diagnosis. To obtain a
karyotype (Fig:21), doctors draw a blood sample to examine the baby's
cells. They use special tools to photograph the chromosomes and then
classify them by size, number, and shape.
By examining the karyotype, doctors can diagnose Down syndrome.
Another genetic test called FISH (Fig:20) can apply similar principles and
confirm a diagnosis in a shorter amount of time ]36[
.
Fig: 20
Fig: 21

25. 24
Treatment
There is no treatment for Down syndrome in this time, but quality
educational programs, a stimulating home environment, good health care,
and positive support from family, friends and the community enable people
with Down syndrome to develop to their full potential and lead fulfilling
lives.
It is important to remember that while children and adults with Down
syndrome experience developmental delays, they also have many talents
and gifts and should be given the opportunity and encouragement to
develop them.
Most children with Down syndrome have mild to moderate impairments
but it is important to note that they are more like other children than they
are different. Early Intervention services should be provided shortly after
birth. These services include physical, speech and developmental therapies.
Fig: 22

26. 25
Most children attend their neighborhood schools, some in regular classes
and others in special education classes. Some children have more significant
needs and require a more specialized program. Some high school graduates
with Down syndrome participate in post-secondary education. Many adults
with Down syndrome are capable of working in the community, but some
require a more structured environment.
Many children with Down syndrome have health complications beyond
the usual childhood illnesses. Approximately 40% of the children have
congenital heart defects. It is very important that an echocardiogram be
performed on all newborns with Down syndrome in order to identify any
serious cardiac problems that might be present. Some of the heart
conditions require surgery while others only require careful monitoring.
Children with Down syndrome have a higher incidence of infection,
respiratory, vision and hearing problems as well as thyroid and other
medical conditions. However, with appropriate medical care most children
and adults with Down syndrome can lead healthy lives. Life expectancy for
people with Down syndrome has increased dramatically in recent decades -
from 25 in 1983 to 60 today. Researchers are making great strides in
identifying the genes on Chromosome 21 that cause the characteristics of
Down syndrome. Many feel strongly that it will be possible to improve,
correct or prevent many of the problems associated with Down syndrome
in the future ]35[
.
Treatment Therapies
A variety of therapies can be used in early intervention programs and
throughout a person's life to promote the greatest possible development,
independence, and productivity.
Some of these therapies are listed below ]37[
.
1. Physical therapy: includes activities and exercises that help build
motor skills, increase muscle strength, and improve posture and
balance. Physical therapy is important, especially early in a child's life,
because physical abilities lay the foundation for other skills. The
ability to turn over, crawl, and reach helps infants learn about the
world around them and how to interact with it.

27. 26
A physical therapist also can help a child with Down syndrome
compensate for physical challenges, such as low muscle tone, in ways
that avoid long-term problems. For example, a physical therapist
might help a child establish an efficient walking pattern, rather than
one that might lead to foot pain ]38[
.
2. Speech-language therapy: can help children with Down syndrome
improve their communication skills and use language more effectively.
Children with Down syndrome often learn to speak later than their
peers. A speech-language therapist can help them develop the early
skills necessary for communication, such as imitating sounds. The
therapist also may help an infant breastfeed because breastfeeding can
strengthen muscles that are used for speech ]37[
. In many cases,
children with Down syndrome understand language and want to
communicate before they can speak. A speech-language therapist can
help a child use alternate means of communication, such as sign
language and pictures, until he or she learns to speak.
Learning to communicate is an ongoing process, so a person with
Down syndrome also may benefit from speech and language therapy
in school as well as later in life. The therapist may help with
conversation skills, pronunciation skills, understanding what is read
(called comprehension), and learning and remembering words.
3. Occupational therapy: helps find ways to adjust everyday tasks and
conditions to match a person's needs and abilities. This type of therapy
teaches self-care skills such as eating, getting dressed, writing, and
using a computer. An occupational therapist might offer special tools
that can help improve everyday functioning, such as a pencil that is
easier to grip. At the high school level, an occupational therapist could
help teenagers identify jobs, careers, or skills that match their interests
and strengths.
4. Emotional and behavioral therapies: work to find useful responses to
both desirable and undesirable behaviors. Children with Down
syndrome may become frustrated because of difficulty
communicating, may develop compulsive behaviors, and may have
Attention Deficit Hyperactivity Disorder and other mental health
issues. These types of therapists try to understand why a child is acting

28. 27
out, create ways and strategies for avoiding or preventing these
situations from occurring, and teach better or more positive ways to
respond to situations.
Drugs and Supplements
Some people with Down syndrome take amino acid supplements or drugs
that affect their brain activity. However, many of the recent clinical trials
of these treatments were poorly controlled and revealed adverse effects
from these treatments. Since then, newer psychoactive drugs that are much
more specific have been developed. No controlled clinical studies of these
medications for Down syndrome have demonstrated their safety and
efficacy, however.
Many studies of drugs to treat symptoms of dementia in Down syndrome
have included only a few participants. The results of these studies have not
shown clear benefits of these drugs, either. Similarly, studies of antioxidants
for dementia in Down syndrome have shown that these supplements are
safe, but not effective ]39[
.
Fig: 23

29. 28
Famous People with
Down Syndrome
Down syndrome is a genetic condition that is caused by an extra
chromosome in the body's cells. People with Down syndrome have
characteristic facial and other physical features. There is a degree of mental
disability associated with this condition. However, this varies from
individual to individual. There may also be some other inherent problems
with some organs of the body like the heart, lungs, ears or intestines. Most
people with Down syndrome can live normal, happy lives with the correct
care and support ]40[
.
1.Luke Zimmerman (Fig:24):
He starred in the series called The Secret Life of the American Teenager.
Although he had been involved in acting for most of his life, the role of the
adopted older brother in this family series is what catapulted him into
celebrity status.
Fig: 24

30. 29
2.Lauren Potter (Fig:25):
Lauren Potter is one of the famous people with Down syndrome. This
blonde actress gained popularity on the TV show Glee.
3.Tommy Jessop (Fig:26):
A star in his own right in the British Documentary Growing Up Down's.
This documentary follows 3 individuals with Down syndrome and their
daily ups and downs as they produce the Shakespeare play, Hamlet. This
British actor has been acting since 2007.
Fig: 25
Fig: 26

31. 30
4.Chris Burke (Fig:27):
Christ Burke is the National Down Syndrome
Society's Goodwill Ambassador since 1994. He has
used his celebrity status to bring awareness to Down
syndrome worldwide. He is famous for his role as the
beloved brother, Corcky of the Thacher family, in the
popular TV show Life Goes On. His other TV
appearances include: ER, Touched by an Angel and
the successful movie Mona Lisa Smile.
5.Angela Bachiller (Fig:28):
Angela Bachiller became the first person with Down syndrome to be
elected a councilwoman in her native Spain. Prior to that, she worked as an
administrative assistant in the department of Social Welfare and Family.
Her favorite pastime activities include reading and travelling. Her hope is
to make a difference to the lives of people with disabilities and educate
people on the normality of those with Down syndrome.
Fig: 27
Fig: 28

32. 31
6.Michael Johnson (Fig:29):
Michael Johnson is a famous painter who has exhibited his artwork at
Vanderbilt University. He has created more than 500 commissioned
paintings and has had his art featured on the cover of American Journal of
Public Health.
7.Jamie Brewer (Fig:30):
Jamie Brewer is another one of the famous people with Down syndrome.
He plays the clairvoyant witch Nan in the popular TV show American
Horror Story: Coven.
Fig: 29
Fig: 30

33. 32
The Summary
Down syndrome, is one of the most important syndromes that is very
common in our world.
Down Syndrome is a genetic defect in the DNA (Trisomy 21), and the patient
with this syndrome have many strange features and symptoms. They have
risk factors on another organs and systems of their bodies.
There is no treatment for this syndrome, but the patient can be combined
with his society by a lot of ways that have been discovering, he can be taught
and learned, he can also create perfect things for another people, they could
be artists, actors, and even inventors.
Finally, we have to make the patients with Down syndrome abler to consort
with normal people.
Fig: 31

34. 33
How to identify
Down Syndrome?
Fig: 32

35. 34
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