Genetic deseases. Down syndrome

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2. A few words about Genetic Diseases What are the risk factors for conceiving a child with Down syndrome?
Single-gene/monogenic Genetic
Diseases
What type of prenatal screening is available for Down syndrome
Multifactorial/Polygonic Genetic
Diseases
How is the diagnosis of Down syndrome made?
Mitochondrial Genetic Diseases What about cognitive impairment in Down syndrome?
Chromosomal Genetic Diseases What other conditions are associated with Down syndrome?
What is Down syndrome? How is Down syndrome managed? What about early intervention
and education for Down syndrome? What are the needs of infants
and preschool children with Down syndrome?
What is Down syndrome? (Video) How do adolescents with Down syndrome develop? What should one
expect for adults with Down syndrome?
Characteristic Features and Symptoms
of Down syndrome
Do individuals with Down syndrome work?
What are the chromosome basics of
Down syndrome
World Down Syndrome Day
How do the extra genes lead to Down
syndrome?
Children with Down Syndrome. Photos
Special English. Health Report. Down syndrome (Video)

3. One of the most important threats for human's health is, undoubtedly, the genetic
diseases . What a genetic disease is? It is a disorder caused by genetic factors and especially
abnormalities in the human genetic material (genome). There are four main types of genetic
disorders. Of course, some of these changes in genome can cause interesting advantages in
specific environments (Darwinian Fitness). But there is no doubt that all these abnormalities
(disorders) bring destructive results to a living being in the present environment.
The four types of (human) Genetic diseases are:
Single-
gene/monogenic
Genetic Diseases
Multifactorial/
Polygenic Genetic
Diseases
Mitochondrial
Genetic Diseases
Chromosomal
Genetic Diseases
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4. In this category the starting point is a mutation/change in one
gene. The next question is how a change in the sequence of
a single gene can cause severe disorders.Genes code for proteins
which are some of the most important tools for theliving beings,
and also take place in the structures of the cells.The results of a
mutation that happens in a part of gene that codes for a functional
part of a protein are unwelcome. The protein is no more functional
and as a result, many severe consequences take place. Almost
6000 single gene disorders are known and it is estimated that 1 of
200 newborns face a single gene genetic disorder. Some of these
are sickle cell anemia, cystic fibrosis, Aicardi
Syndrome, Huntington's disease .
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5. The second type of human genetic
diseases is caused by mutations in
more than one genes. The
environment combines with these
mutations in order these diseases to
appear. We can easily conclude that
polygenic disorders are more
complicated than the previous type
(single gene diseases). These
abnormalities are also difficult to
analyze, because there are many
factors that researchers should take
into consideration in order to reach to
some useful conclusions. Many well
known chronic diseases are
Multifactorial Genetic
Diseases. Everybody
knows Alzheimer, diabetes, obesity a
nd arthritis .Besides many cancer
types are caused by multi mutations.
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6. It is not a common
situation. Mitochondrial
DNA is a DNA molecule
found in the mitochondria
(out of the nucleous) – a
necessary organelle for
cellular
respiration. Mutations in
the mitochondrial DNA can
also cause undesirable
abnormalities.
In the following pages you
can find more info about
some of the most
dangerous human genetic
diseases and also reveal the
secrets of some rare
disorders.
An example of "ragged red fibers" in MELAS syndrome.
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7. Chromosomes are big DNA
molecules composed from
genes. The chromosomes are
located in the cell
nucleus. Abnormalities in the
structure, number (and not only) of
the chromosomes can cause some
of the most dangerous genetic
disorders. This type of disorders
seem to be much easier to observe
because they are, sometimes,
detected by examination with
microscope. Down Syndrome is
the most well known disease
caused by chromosomal
abnormalities. In this disorder
there is a third copy of
chromosome 21 (there are two
copies of each ch romosome in the
cells of healthy
humans).Chromosomal diseases
can be also caused by segments
and joins of parts of chromosomes.
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8. Down syndrome (also called Trisomy 21) is a
genetic disorder that occurs in approximately 1 of
800 live births. It is the leading cause of cognitive
impairment. Down syndrome is associated with
mild to moderate learning
disabilities, developmental delays, characteristic
facial features, and low muscle tone in early
infancy. Many individuals with Down syndrome
also have heart defects, leukemia, early-onset
Alzheimer’s disease, gastro-intestinal problems,
and other health issues. The symptoms of Down
syndrome range from mild to severe.
Life expectancy for individuals with Down
syndrome has dramatically increased over the past
few decades as medical care and social inclusion
have improved. A person with Down syndrome in
good health will on average live to age 55 or
beyond.
Down syndrome is named after Doctor Langdon
Down, who in 1866 first described the syndrome
as a disorder. Although Doctor Down made some
important observations about Down syndrome, he
did not correctly identify what causes the disorder.
It wasn't until 1959 that scientists discovered the
genetic origin of Down syndrome.
Karyotype for trisomy Down syndrome. Notice the
three copies of chromosome 21
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10. Although the severity of Down syndrome ranges
from mild to severe, most individuals with
Down syndrome have widely recognizable
physical characteristics. These include:
a flattened face and nose, a short neck, a
small mouth sometimes with a large, protruding
tongue, small ears, upward slanting eyes that
may have small skin folds at the inner corner
(epicanthal fold);
white spots (also known as Brushfield spots)
may be present on the colored part of the eye
(iris);
the hands are short and broad with short
fingers, and with a single crease in the palm;
poor muscle tone and loose ligaments are also
common; and
development and growth is usually delayed
and often average height and developmental
milestones are not reached.
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11. Genes on an extra copy of chromosome 21 are responsible for all characteristics associated with Down
syndrome. Normally, each human cell contains 23 pairs of different chromosomes. Each chromosome
carries genes, which are needed for proper development and maintenance of our bodies. At conception,
an individual inherits 23 chromosomes from the mother (through the egg cell) and 23 chromosomes from
the father (through the sperm cell).
However, sometimes a person inherits an extra chromosome from one of the parents. In Down syndrome,
an individual most often inherits two copies of chromosome 21 from the mother and one chromosome 21
from the father for a total of three chromosomes 21. Because Down syndrome is caused by the inheritance
of three chromosomes 21, the disorder is also called trisomy 21. About 95% of individuals with Down
syndrome inherit an entire extra chromosome 21.
Approximately 3% to 4% of individuals with Down syndrome do not inherit an entire extra chromosome 21,
but just some extra chromosome 21 genes, which are attached to another chromosome (usually
chromosome 14). This is called a translocation. Most of the time, translocations are random events during
conception. In some instances however, a parent is a balanced carrier of a translocation: The parent has
exactly two copies of chromosome 21, but some of the genes are distributed to another chromosome. If a
baby inherits the chromosome with the extra genes from chromosome 21, then the child will have Down
syndrome (two chromosomes 21 plus extra chromosome 21 genes attached to another chromosome).
About 2% to 4% of people with Down syndrome inherit additional genes from chromosome 21, but not in
every cell of the body. This is known as mosaic Down syndrome. These individuals may, for example, have
inherited extra genes from chromosome 21 in their muscle cells, but not in any other type of cell. Because
the percentage of cells with extra genes from chromosome 21 varies in people with mosaic Down syndrome,
they often don't have all the typical physical characteristics and may not be as severely intellectually
impaired as people with full trisomy 21. Sometimes, mosaic Down syndrome is so mild that it will go
undetected. On the other hand, mosaic Down syndrome can also be misdiagnosed as trisomy 21, if no
genetic testing has been done.
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12. Exactly how the extra genes from
chromosome 21 lead to Down syndrome is
still not clear. Scientists believe that the
increased presence of specific genes alters
the interaction between these and other
genes. Some genes will become more
active and others less active than normal,
leading to changes in the development
and maintenance of the body. Why some
individuals are more severely affected
than others might have to do with how
many and which specific extra genes were
inherited.
Scientists are trying to find out which
genes from chromosome 21, when
present in three copies, are responsible for
the different characteristics of Down
syndrome. Currently, about 400 genes on
chromosome 21 have been identified, but
the functions of most are still unknown.
Through human studies and animal
models, scientists are making progress in
understanding the functions of individual
genes.
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13. The only well known risk factor for conceiving a child
with Down syndrome is advanced maternal age. The
older the woman is at conception, the greater the risk
of having a child with Down syndrome.
Mother's age at conception Risk of Down syndrome
25 years 1 in 1,250
30 years 1 in 1,000
35 years 1 in 400
40 years 1 in 100
45 years 1 in 30
Parents who have conceived a child with Down
syndrome have a 1% increased risk of conceiving
another child with Down syndrome. If a parent is a
carrier of a chromosome 21 translocation, the risk can
be as high as 100%.
Women with Down syndrome have a 50% risk of
conceiving a child with Down syndrome. If the father
has Down syndrome, the risk of conceiving a child with
Down syndrome is also increased.
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14. Several noninvasive screening options are offered to parents. If Down syndrome is suspected due to the screening
outcome, a formal diagnosis can be made before the baby arrives. This gives parents time to gather information
about Down syndrome before their baby is born and to make arrangements in case of medical complications.
Prenatal screening tests currently available include the expanded alpha-fetoprotein (AFP) screening test, the
nuchal translucency test, and additional ultrasound screens which look for changes in certain anatomical features
of the fetus. While these screening tests can assess the risk for Down syndrome, they cannot confirm Down
syndrome with certainty.
The most widely used screening test is the AFP. Between weeks 15 and 20 of pregnancy, a small blood sample is
taken from the mother and examined. The levels of AFP and three hormones called unconjugated estriol, human
chorionic gonadotropin, and inhibin-A are measured in the blood sample. If the AFP and hormone levels are
altered, Down syndrome can be suspected, but not confirmed. Likewise, a normal test result does not rule out
Down syndrome.
The nuchal translucency test measures the thickness of the fold in the neck via ultrasound. This test can be done
between 11 and 13 weeks of pregnancy. In combination with the mother's age, this test identifies about 80% of
Down syndrome fetuses.
Women considered at high risk (advanced maternal age, positive AFP test, or a history of a previous child with
Down syndrome) may benefit from additional ultrasound scans between 18 and 22 weeks of pregnancy. When
certain anatomical features are altered, absent, or present in a fetus, it may indicate Down syndrome. Some of the
markers that are examined include:
the length of the nasal bridge,
the size of the renal pelvis (hypoplasia, pyelectasis),
small bright spots in the heart (echogenic intracardiac
foci),
small middle section of the little finger (hypoplastic
fifth digit),
a large gap between the first and second toe,
increased brightness of the bowel (echogenic
bowel), and
pelvic bone angle (widened iliac angle).
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15. The diagnosis of Down syndrome can be made
before birth using one of several diagnostic tests.
These tests carry a small risk of miscarrige.
If Down syndrome is suspected after a child is born,
a diagnosis can be made via chromosome analysis.
Amniocentesis is performed between 16 and 20
weeks of pregnancy. During this procedure, a thin
needle is inserted through the abdominal wall and a
small sample of amniotic fluid is taken. The sample is
analyzed for chromosome anomalies.
Chorionic villus samping (CVS) is done between 11
and 12 weeks of pregnancy. It involves the collection
a chorionic villus cell sample from the placenta
either through insertion of a needle in the
abdominal wall or through a catheter in the vagina.
The chromosomes in CVS are analyzed for
deviations.
For percutaneous umbilical blood sampling (PUB),
fetal blood is taken from the umbilical cord using a
needle inserted through the abdominal wall. The
blood sample is examined for chromosome
abnormalities. It is usually performed after week 18.
Ultrasound of fetus with Down
syndrome and megacystis
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16. The most common condition associated
with Down syndrome is cognitive
impairment. Cognitive development is
often delayed, and all individuals with
Down syndrome have mild to severe
learning difficulties that last throughout
their lives. How the extra chromosome 21
leads to cognitive impairment is not
entirely clear. The average brain size of a
person with Down syndrome is small and
scientists have found alterations in the
structure and function of certain brain
areas such as the hippocampus and
cerebellum. Particularly affected is the
hippocampus, which is responsible for
learning and memory. Scientists are using
human studies and animal models of
Down syndrome to find out which
specific genes on the extra chromosome
21 lead to different aspects of cognitive
impairment.
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17. Heart conditions
Apart from cognitive
impairment, the most
common medical
conditions associated
with Down syndrome
are congenital heart
defects. About half of
all people with Down
syndrome are born with
a heart defect, often
with an atrioventricular
septal defect. Other
common heart defects
occurring in Down
syndrome
include ventricular
septal defect, atrial
septal defect, tetralogy
of Fallot, and patent
ductus arteriosus. Some
babies will require
surgery shortly after
birth to correct these
heart defects.
Gastrointestinal conditions
Gastrointestinal conditions are also
commonly associated with Down syndrome,
especially esophageal atresia,
tracheoesophageal fistula, duodenal atresia
or stenosis, Hirschsprung disease, and
imperforate anus. Individuals with Down
syndrome are at a higher risk for
developingceliac disease. Corrective surgery
is sometimes necessary for gastrointestinal
problems.
Cancer
Certain types of cancer are
more frequently found in
Down syndrome, such as
acute lymphoblastic
leukemia (a type of blood
cancer), myeloid leukemia,
and testicular cancer. Solid
tumors on the other hand
rarely occur in this
population.
Other conditions
Other medical conditions include:
•hearing loss,
•frequent ear infections (otitis media),
•underactive thyroid (hypothyroidism),
•cervical spine instability,
•visual impairment,
•sleep apnea,
•obesity,
•constipation,
•infantile spasms,
•seizures,
•dementia, and
•early-onset Alzheimer's disease.
About 18% to 38% of individuals
with Down syndrome have
coexisting psychiatric or behavior
conditions, such as:
•autism spectrum disorders,
•attention deficit hyperactivity
disorder (ADHD),
•depression,
•stereotypical movement
disorders, and
•obsessive compulsive disorder.
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18. How is Down syndrome managed?
Although the genetic cause of Down
syndrome is known, there is currently no
cure. Due to advances in technology,
scientists are slowly beginning to
understand which genes when present in
three copies are responsible for which Down
syndrome characteristics, but it will take
many years to fully grasp the complex
interplay between the different genes. Much
research to date is focused on
understanding the causes of impaired
cognition in Down syndrome and on finding
potential therapies that might improve
learning. Most of these studies are carried
out using animal models of Down syndrome,
but some human clinical trials involving
potential therapies are also being
conducted.
Corrective surgery for heart defects,
gastrointestinal irregularities, and other
health issues is necessary for some
individuals. Regular health checkups should
be scheduled to screen for other conditions
such as visual impairments, ear infections,
hearing loss, hypothyroidism, obesity, and
other medical conditions.
Individuals with Down syndrome should be
fully included in family and community life.
What about early intervention and
education for Down syndrome?
It is very important to stimulate, encourage,
and educate children with Down syndrome
from infancy. Programs for young children
with special needs are offered in many
communities. Early intervention programs,
including physical therapy, occupational
therapy, and speech therapy can be very
helpful.
What are the needs of infants and
preschool children with Down syndrome?
Like all children, children with Down
syndrome greatly benefit from being able to
learn and explore in a safe and supportive
environment. Being included in family,
community, and preschool life will help a
child with Down syndrome develop to his or
her full potential.
While social development and social
learning are often quite good, development
in other areas such as motor skills, speech,
and language are usually delayed. Many
children with Down syndrome eventually
reach most developmental milestones, but
mild to severe learning difficulties will
persist throughout life.
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19. How do adolescents with Down syndrome
develop?
Adolescents with Down syndrome undergo the
same hormonal changes during pubertyas typically
developing children. Girls with Down syndrome
have regular menstrual periods and should receive
instructions on hygiene. Although women with
Down syndrome are not very fertile, they can
become pregnant. Men with Down syndrome have
low sperm count, but in some cases have fathered
children. Proper education regarding sexual
development and contraception is very important.
What should one expect for
adults with Down syndrome?
Individuals with Down
syndrome live longer than ever
before. Due to full inclusion in
society, many adults with Down
syndrome now live semi-
independently, enjoy
relationships, work, and
contribute to their community.
Adults with Down syndrome also age faster than average. The older they become, the
higher the risk of developing hypothyroidism, late-onset seizures (tonic-clonic seizures in
particular), memory loss, and dementia. By age 40, many individuals with Down syndrome
will show signs of dementia and early-onset Alzheimer's disease. By age 60, 50% to 70% of
adults will develop Alzheimer's disease. Why individuals with Down syndrome age
prematurely and why they develop Alzheimer's disease is not entirely clear. At least one
gene (the amyloid precursor protein) on chromosome 21 is thought to be involved in
Alzheimer's disease. Since individuals with Down syndrome have three copies of this gene,
it is likely that this gene contributes to the increased occurrence of Alzheimer's disease in
this population. Detecting dementia and early signs of Alzheimer's disease is a
challenge in individuals with Down syndrome who are often
already cognitively impaired. It is important for caregivers and
doctors to be aware of changes in skills necessary for
independence.
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20. While some individuals with Down syndrome
find suitable paid employment, many others
are volunteers, or hold no job. Individuals
with Down syndrome who wish to work
should receive adequate training and support.
This is not always readily available in all
communities at present. In addition,
employers should be made more aware of the
benefits of employing someone with Down
syndrome.
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21. World Down Syndrome Day (WDSD), is on 21 March.
On this day, Down Syndrome organizations throughout
the world organize and participate in events to raise
public awareness of Down syndrome.
Down syndrome was first determined a chromosomal
disorder in 1959 by French pediatrician and
geneticist, Jérôme Lejeune. Down syndrome is a very
real and important subject because people with Down
syndrome are constantly affecting peoples lives in many
mays. One in every 733 babies is born with Down
syndrome.n the United states, alone, there are more
than 400,000 people living with Down syndrome.
The date was selected by Down Syndrome
International (DSI) to signify the uniqueness of Down
syndrome in the triplication (trisomy) of the 21st
chromosome and is used synonymously with Down
syndrome. The original idea was proposed by Stylianos
E. Antonarakis, a medical geneticist of the University of
Geneva Medical School, and enthusiastically adopted
by ART21, a patient group for the Lemanic region of
Switzerland. The first events were organized on 21
March 2006 in Geneva.
The inaugural WDSD was launched on 21 March 2006
in Singapore, with events organized by the Down
Syndrome Association.
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24. Bibliography C
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Arron JR, Winslow MM, Polleri A (2006). «NFAT
dysregulation by increased dosage of DSCR1 and DYRK1A
on chromosome 21»
Epstein CJ (June 2006). «Down's syndrome: critical
genes in a critical region»
Ganong, W.J. (2005). Review of Medical Physiology (21st
ed.). New York: Mc-Graw Hill
Nelson DL, Gibbs RA (2004). "Genetics. The critical
region in trisomy 21". Science (journal)
Olson LE, Richtsmeier JT, Leszl J, Reeves RH (2004). "A
chromosome 21 critical region does not cause specific
Down syndrome phenotypes". Science (journal)
Hattori M, Fujiyama A, Taylor TD (2000). "The DNA
sequence of human chromosome 21"