1.
Down Syndrome
Abbas A. A. Shawka

2.
Objectives
At the end of this lecture you SHOULD be able to answer these
questions :-
What is Down Syndrome?
How it is formed?
What are the cytogenetic types?
How to write & interpret the karyotype?
Do different cytogenetic types have different clinical features?
What are the clinical features of Down Syndrome?
Is there any special situation in Diagnosis of Down syndrome?
How to deal with a child with Down syndrome (i.e.
Management)?
Is there any method to diagnose Down syndrome babies before
they were born (during pregnancy)?

3.
Down syndrome
• Down syndrome also known as trisomy 21, is
a genetic disordercaused by the presence of all or
part of a third copy of chromosome 21. It is
typically associated with physical growth delays,
characteristic facial features and mild to
moderate intellectual disability.
• Down syndrome is one of the most
common chromosome abnormalities in humans.It
occurs in about one per 1000 babies born each year. In
2015, Down syndrome was present in 5.4 million
individuals and resulted in 27,000 deaths down from
43,000 deaths in 1990. It is named after John Langdon
Down, the British doctor who fully described the
syndrome in 1866. Some aspects of the condition were
described earlier by Jean-Étienne Dominique Esquirol in
1838 and Édouard Séguin in 1844. In 1957, the genetic
cause of Down syndrome, an extra copy of
chromosome 21, was discovered.

4.
What cause DS ?!

5.
What cause DS ?!

6.
What cause DS ?!

7.
What cause DS ?!

8.
Cytogenetics and karyotyping
• So, the cytogenetic types of DS with karyotype are
1. Trisomy 21 (47,XX,+21)
2. Robertsonian tranlocation [46,XX,t(14;21)] or
[45,XX,t(21;21)(q10;q10)]**
3. Mosaicism (46,XX/47,XX,+21)
4. Duplication of part of chromosome
• The long arm of chromosome 21 is attached to the
long arm of another chromosome,
often chromosome 14 [46,XX,t(14;21)] or itself
[called an isochromosome, [45,XX,t(21;21)(q10;q10)]

9.
Trisomy 21

10.
Robertsonian translocation

11.
Mosaicism

12.
How isochromosme can produce down syndrome ?!

13.
Clinical feature vs. cytogenetics
• The degree of problems depends on the number of
cells in the person's body that are affected by
trisomy. ( in mosaic Down syndrome )

14.
Findings in DS

15.
Down syndrome testing
• A prenatal screening test. This test can show an
increased likelihood that a fetus has Down
syndrome, but it cannot determine Down
syndrome is definitely present. If a screening test
shows an increased likelihood, a diagnostic test can
be ordered.
• A prenatal diagnostic test. This test can determine
with certainty that Down syndrome is present.
Diagnostic tests carry a slightly greater risk to the
fetus than do screening tests.

16.
Prenatal screening tests
• A blood test and an ultrasound test during the first trimester of
pregnancy. This is the most accepted approach for screening
during the first trimester. A blood test enables a health care
provider to check for "markers," such as certain proteins, in the
mother's blood that suggest an increased likelihood of Down
syndrome.2 Then the health care provider does an ultrasound
test, which uses high-frequency sound waves to create images.
An ultrasound can detect fluid at the back of a fetus's neck,
which sometimes indicates Down syndrome. The ultrasound
test is called measurement of nuchal translucency. During the
first trimester, this combined method results in more effective
or comparable detection rates than methods used during the
second trimester.3
• A blood test during the second trimester of pregnancy. As in the
first trimester, a blood test enables a health care provider to
check for markers in the mother's blood. A triple screen looks
for levels of three different markers; a quadruple screen looks
for levels of four different markers.3,4
• A combined test (sometimes called an integrated test). This
approach uses both a blood test and an ultrasound during the
first trimester as well as a second-trimester blood test. Health
care providers then combine all these results to produce one
Down syndrome risk rating.2

17.
Prenatal diagnositic tests
• Amniocentesis (pronounced am-nee-oh-sen-TEE-sis). A health care
provider takes a sample of amniotic (pronounced am-nee-OT-ik) fluid,
which is then tested for the extra chromosome. This test cannot be
done until week 14 to 18 of the pregnancy.
• Chorionic villus (pronounced KOHR-ee-on-ik VIL-uhs) sampling (CVS). A
health care provider takes a sample of cells from a part of the placenta
(pronounced pluh-SEN-tuh), which is the organ that connects a woman
and her fetus, and then tests the sample for the extra chromosome.
This test is done between weeks 9 and 11 of pregnancy.
• Percutaneous (pronounced pur-kyoo-TEY-nee-uhs) umbilical blood
sampling (PUBS). A health care provider takes a sample of fetal blood
in the umbilical cord through the uterus. The blood is then tested for
the extra chromosome. PUBS is the most accurate diagnostic method
and can confirm the results of CVS or amniocentesis. However, PUBS
cannot be performed until later in the pregnancy, during the 18th to
22nd week.5

18.
Prenatal diagnositic tests
• Prenatal diagnostic testing does involve some risk to
the mother and fetus, including risk of miscarriage
that ranges from less than 1% to 2%.6,7,8,9 If you and
your family are considering prenatal diagnostic testing
for Down syndrome, discuss all the risks and benefits
with your health care provider.
• Chromosomal Testing of Maternal Blood
• A pregnant woman who is at risk for having an infant
with Down syndrome also can have a chromosomal
test using her blood. A mother's blood carries DNA
from the fetus, which may show extra chromosome 21
material. A more invasive test then would usually
confirm the blood test.

19.
Management
• Down syndrome is incurable and efforts to manage the
condition are focused on early childhood intervention,
education and proper support and care. Some individuals with
Down syndrome may only experience mild complications
associated with the condition while others may be affected by
more severe problems such as congenital heart defect or a “hole
in the heart.” Some of the aspects involved in caring for children
with Down syndrome are described below.
• Detecting problems at birth
• Various health organizations have advised the systematic
screening for certain diseases in babies born with Down
syndrome. Some of the diseases infants may be affected by
include thyroid disease, Hirschsprung’s disease, cataracts,
leukaemia and heart defects. Other problems include hearing
loss, obstructive sleep apnea, anemia and intestinal blockage.
• Children born with Down syndrome should undergo an
echocardiogram, as around half of those with the condition
have a heart defect. To detect intestinal abnormalities, an
abdominal ultrasound is recommended and hearing defects are
checked for using brainstem auditory evoked responses
(BAERS). A complete blood count is obtained in order to check
for leukemia and the thyroid gland is also tested.

20.
Management
• Correcting health conditions
• Children with a heart defect may require surgical repair when they are as
young as 3 years of age. Among those with hearing loss, hearing aids and
speech therapy may help children with learning language. Sign language is
another alternative. Any behavioural illnesses are usually handled with the
help of talking therapy and/or drugs.
• Managing delay in cognitive development
• Down syndrome is the most common cause of learning disability in children
and most have mild to moderate mental intellectual disability, with IQs ranging
from 70 to 35. Some individuals have an even lower IQ (of 20 to 35) and
experience severe difficulties. However, early intervention programs can help
infants to improve their cognitive abilities and develop to their full potential.
Examples of services that can be offered through early intervention programs
include speech therapy, language therapy and occupational therapy.
• Some individuals may opt for cosmetic or plastic surgery to alter some of their
facial features. However, this approach is considered controversial and the
National Down Syndrome Society encourages people to focus on mutual
respect and acceptance rather than appearance.
• The care team involved in the management of Down syndrome may include a
number of individuals from various disciplines such as a paediatrician or child
specialist, a physiotherapist, a speech and language therapist, an occupational
therapist, an otolaryngorhinologist or ENT specialist, an ophthalmologist, a
heart specialist and a gastroenterologist.

21.
Thank You