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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 interventionand 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)

One of the most important threats for human's health is, undoubtedly, the geneticdiseases . What a genetic disease is? It is a disorder caused by genetic factors and especiallyabnormalities in the human genetic material (genome). There are four main types of geneticdisorders. Of course, some of these changes in genome can cause interesting advantages inspecific 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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In this category the starting point is a mutation/change in onegene. The next question is how a change in the sequence ofa single gene can cause severe disorders.Genes code for proteinswhich are some of the most important tools for theliving beings,and also take place in the structures of the cells.The results of amutation that happens in a part of gene that codes for a functionalpart of a protein are unwelcome. The protein is no more functionaland as a result, many severe consequences take place. Almost6000 single gene disorders are known and it is estimated that 1 of200 newborns face a single gene genetic disorder. Some of theseare sickle cell anemia, cystic fibrosis, AicardiSyndrome, Huntington's disease .

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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 and arthritis .Besides many cancer

types are caused by multi mutations.

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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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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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Down syndrome (also called Trisomy 21) is agenetic disorder that occurs in approximately 1 of800 live births. It is the leading cause of cognitiveimpairment. Down syndrome is associated withmild to moderate learningdisabilities, developmental delays, characteristicfacial features, and low muscle tone in earlyinfancy. Many individuals with Down syndromealso have heart defects, leukemia, early-onsetAlzheimer’s disease, gastro-intestinal problems,and other health issues. The symptoms of Downsyndrome range from mild to severe.Life expectancy for individuals with Downsyndrome has dramatically increased over the pastfew decades as medical care and social inclusionhave improved. A person with Down syndrome ingood health will on average live to age 55 orbeyond.Down syndrome is named after Doctor LangdonDown, who in 1866 first described the syndromeas a disorder. Although Doctor Down made someimportant observations about Down syndrome, hedid not correctly identify what causes the disorder.It wasn't until 1959 that scientists discovered thegenetic origin of Down syndrome.

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

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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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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 chromosomecarries 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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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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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 1,25030 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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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 intracardiacfoci), small middle section of the little finger (hypoplasticfifth digit),

a large gap between the first and second toe,increased brightness of the bowel (echogenicbowel), andpelvic bone angle (widened iliac angle).

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The diagnosis of Down syndrome can be madebefore 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 20weeks of pregnancy. During this procedure, a thinneedle is inserted through the abdominal wall and asmall sample of amniotic fluid is taken. The sample isanalyzed for chromosome anomalies.Chorionic villus samping (CVS) is done between 11and 12 weeks of pregnancy. It involves the collectiona chorionic villus cell sample from the placentaeither through insertion of a needle in theabdominal wall or through a catheter in the vagina.The chromosomes in CVS are analyzed fordeviations.For percutaneous umbilical blood sampling (PUB),fetal blood is taken from the umbilical cord using aneedle inserted through the abdominal wall. Theblood sample is examined for chromosomeabnormalities. It is usually performed after week 18.

Ultrasound of fetus with Down syndrome and megacystis

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The most common condition associatedwith Down syndrome is cognitiveimpairment. Cognitive development isoften delayed, and all individuals withDown syndrome have mild to severelearning difficulties that last throughouttheir lives. How the extra chromosome 21leads to cognitive impairment is notentirely clear. The average brain size of aperson with Down syndrome is small andscientists have found alterations in thestructure and function of certain brainareas such as the hippocampus andcerebellum. Particularly affected is thehippocampus, which is responsible forlearning and memory. Scientists are usinghuman studies and animal models ofDown syndrome to find out whichspecific genes on the extra chromosome21 lead to different aspects of cognitiveimpairment.

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Heart conditionsApart 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 atrioventricularseptal defect. Other

common heart defects occurring in Down

syndrome include ventricular septal defect, atrial

septal defect, tetralogyof Fallot, and patent

ductus arteriosus. Some babies will require

surgery shortly after birth to correct these

heart defects.

Gastrointestinal conditionsGastrointestinal conditions are also commonly associated with Down syndrome, especially esophageal atresia, tracheoesophageal fistula, duodenal atresiaor 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.

CancerCertain 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 conditionsOther 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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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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How do adolescents with Down syndrome develop?

Adolescents with Down syndrome undergo thesame hormonal changes during pubertyas typicallydeveloping children. Girls with Down syndromehave regular menstrual periods and should receiveinstructions on hygiene. Although women withDown syndrome are not very fertile, they canbecome pregnant. Men with Down syndrome havelow sperm count, but in some cases have fatheredchildren. Proper education regarding sexualdevelopment and contraception is very important.

What should one expect for adults with Down syndrome?

Individuals with Downsyndrome live longer than everbefore. Due to full inclusion insociety, many adults with Downsyndrome now live semi-independently, enjoyrelationships, work, andcontribute 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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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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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 StylianosE. 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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Bibliography CONTENTS

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 HillNelson 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"