Children born with Down syndrome (DS) have an excessive amount of the chromosome 21 in some or all of their cells. This chromosomal abnormality often causes characteristic physical traits in people with DS as well as developmental delays and mental retardation.Single deep crease across the palm. Joint Laxity. Excessive space between 1st and 2nd toe. Small mouth enlarged tongue.small nose with depressed nasal bridge.upward slant to the eyes. Abnormally shaped ears. The vast majority of people with DS carry an extra copy of chromosome 21 in every cell in their bodies. Normally, human cells all contain 23 pairs of chromosomes for a total of 46. AN UNAFFECTED MALE 
KARYOTYPE:  46, XYA MALE DOWN SYNDROME 
KARYOTYPE: 47, XY, +21There are three genetic forms of Down syndrome: non-disjunction, mosaicism, and translocation. Non-disjunction is the most common, and individuals with this form have an entire extra chromosome in all their cells. Non-disjunction is a result of faulty chromosome separation during cell division in egg or sperm cell production.  This type of cell division is called meiosis.   As the cells divide, the 23 pairs of chromosomes are supposed to split up and head to opposite sides in the dividing cell. (In the cell below, only one chromosome pair is shown.) Meiosis involves a series of stages that ultimately reduce the number of chromosomes from 46 to 23. Meisois ensures that the resulting gametes, sperm or egg cells, will have 23 single chromosomes. (In cells below, we only show one chromosome. But remember, there are actually 23 in each newly formed cell.) When fertilization occurs, the resulting embryo will have a total of 46 chromosomes ø 23 pairs. But things can go wrong during meiosis.  

The initial stages of meiosis may run smoothly... ...however; sometimes in later stages, one pair of chromosomes fails to separate and both chromosomes go to one side of the dividing cell. This cell-division mistake is called non-disjunction. When non-disjunction occurs, the resulting gametes will have an abnormal chromosome count. One cell will have 22 single chromosomes and the other will have 24. Non-disjunction results in Down syndrome when an egg or sperm cell with two 21 chromosomes merges with a normal mate (one 21 chromosome). 24  SINGLE CHROMOSOMES IN EGG CELL 23  SINGLE CHROMOSOMES IN SPERM CELL As the embryo develops, the extra 21 chromosome is replicated in every cell of its body. Fertilization of an egg cell by a faulty sperm cell can cause Down syndrome, but recent research implicates abnormal egg cells in the majority of cases. Despite years of research, no one knows what causes non-disjunction to occur. Mosaic Down syndrome (mosaicism) is rare and accounts for only 1% to 2% of those with DS. As the name implies, those affected have a mixture of cell types in their bodies.  Some cells are normal and contain 46 chromosomes, while others contain 47, carrying an extra copy of chromosome 21. Mosaic DS is further sub-divided by how the mixture of cells occurs in the body. When different cells of the same type are mixed this is called cellular mosaicism. NERVE CELLS WITH 46 CHROMOSOMES NERVE CELLS WITH 47 CHROMOSOMES When one set of cells (kidney for example) has the normal number of chromosomes, and another cell set (say nerve cells) has an extra  chromosome 21, this is called tissue mosaicism. NERVE CELLS WITH 47 CHROMOSOMES KIDNEY CELLS WITH 46 CHROMOSOMES Mosaicism results from a non-disjunction error that occurs immediately after fertilization.  Recent research seems to indicate that the majority of cases of mosaicism happen when a zygote with the most common form of DS (non-disjunction trisomy 21) loses the extra 21 chromosome in certain dividing cells. This creates "lineages" of cells with or without the extra chromosome. The third form of DS results from what is known as a Robertsonian translocation, and accounts for approximately 4% of DS cases. Translocation DS occurs when part of the chromosome 21 breaks off during meiotic cell division and latches onto another chromosomal body (usually number 14). When a gamete with such a translocation error merges with a normal egg or sperm cell, the result is a triplication of chromosome 21 material. However, because the extra portion of chromosome 21 is fused with  chromosome 14, the total number of chromosomes in each cell is a normal count of 46. Translocations resulting in DS can either be sporadic, chance events of faulty cell division or may be inherited. TRANSLOCATION KARYOTYPE Doctors often suspect the diagnosis of Down syndrome at birth from the physical appearance of the newborn. When Down syndrome is suspected, a genetic test is done to study the baby's chromosomes.  This test is called a karyotype, and it represents the entire chromosomal makeup of an individual. To perform a karyotype, cells that divide often are needed.  Because lymphocytes divide readily and are easy to obtain from blood, these cells are frequently used to test for Down syndrome. Heparin, an anti-clotting agent, is added to this blood sample, which is then put into a centrifuge.  The blood sample is then spun in the centrifuge, thus separating out the various blood cell types.  

Once separated, these lymphocytes are placed on a growth culture and encouraged to divide (undergo mitosis). Because dividing cells show off their chromosomes best at the mid-stage of cell division called metaphase, a drug is added to the dividing cells to halt mitosis. These lymphocytes (with their cell division halted) are taken from the culture and treated with a solution that causes them to swell.  This swelling untangles the metaphase chromosomes, pushing them apart.   The puffed up cells are placed on a slide, stained with a dye and then viewed under a microscope.  A photograph of the slide is taken and enlarged for a final matching up of the chromosomes.  The final step is to cut the photo apart (computers do this now) and pair up matching chromosomes.  A child with Down syndrome will have a karyotype with either three chromosome 21s or a translocated 21.  A child with Down syndrome will have a karyotype showing either three  chromosome 21s or a translocated 21.  If the child has mosaic Down syndrome, some cells will have the normal 46 chromosomes, while others will have 47 with three 21s. Most pregnant women undergo a blood test to screen for Down syndrome around the 15th week of their pregnancy.  This test looks at three different chemicals in the woman’s blood and is used to estimate the risk of Down syndrome in her fetus.  This test, called a triple screen, measures the amount of Alpha-fetoprotein Plus, human chorionic gonadotropin, and estradiol in the mother’s blood.  The test results are combined with the age of the mother and an estimate of risk is made. AFP - LOW LEVELS MAY INDICATE DOWN SYNDROME HCG - HIGH LEVELS MAY INDICATE DOWN SYNDROME ESTRADIOL - LOW LEVELS MAY INDICATE DOWN SYNDROME If the blood work is normal and the woman is under 35, no further testing is recommended.  However, if the woman is over 35, or if the triple screen testing is abnormal, further testing is recommended to the woman.

 PREGNANT WOMAN 
UNDER 35 YEARS OF AGE TRIPLE SCREEN TEST NORMAL = NO FURTHER TEST ANY PREGNANT WOMAN TRIPLE SCREEN TEST ABNORMAL = FURTHER TEST FOR DS RECOMMENDED ANY PREGNANT WOMAN 
OVER 35 YEARS OF AGE FURTHER TEST FOR DOWN SYNDROME RECOMMENDED The triple screen only picks up 60% of Down syndrome cases prenatally.  Three other prenatal tests are used to diagnosis Down syndrome:  amniocentesis, chorionic villus sampling, and percutaneous umbilical cord sampling — all three are invasive and carry a small risk of miscarriage.  Frequently, amniocentesis is the prenatal test used to diagnosis DS. DIAGNOSTIC TEST AMNIOCENTESIS – 99.8% ACCURATE Amniocentesis is performed by inserting a long, thin needle through the mother’s abdominal wall and extracting a small amount of fluid that bathes the developing fetus.  This amniotic fluid contains fetal skin cells that can be used to perform a karyotype.  If the fetus's karyotype shows either three chromosome 21s or an excess of chromosome 21 translocated onto another chromosome, a diagnosis of Down syndrome is made. If the fetus's karyotype shows either three chromosome 21s or an excess of chromosome 21 translocated onto another chromosome, a diagnosis of Down syndrome is made. Researchers are currently working to develop less invasive diagnostic testing that can be performed in the first 12 weeks of pregnancy. Translocation Down syndrome is the only form of the disorder that can be inherited Ñ passed from parent to child.  Approximately one-half of all translocation cases are inherited.  A person inherits Down syndrome (DS) from a parent who carries a translocated chromosome 21.   Remember, translocation occurs when a part of a chromosome or whole chromosome breaks off and attaches to another chromosome. Often, the carrier parent is unaffected because his or her swapped portion of chromosomal material is balanced Ñ there is no extra 21 chromosomal material.  A carrier parent can have a DS child, or a balanced carrier like the parent, or a child with normal chromosomes.  For male carriers, the risk is only 3%.  Researchers are not sure why this difference exists. When a baby is born with translocation Down syndrome, the parents should both be tested to determine if either parent carries a translocated  chromosome 21.  If either the mother or father is a carrier, then the baby has inherited Down syndrome.  If neither parent is a carrier, the Down syndrome is a result of faulty cell division. Men with Down syndrome are essentially sterile and cannot reproduce.  (There is a potential for men with mosaicism to father a child, but this is extremely rare.)  The process of sperm production is stopped or "arrested" in men with Down syndrome.  During meiosis, the presence of the third, unpaired chromosome 21 causes the dividing cell to die and no viable sperm are produced. 

 Women with Down syndrome are able to produce egg cells and have babies.  (Researchers are not clear why egg production is not "arrested" in females during meiosis.)  A woman with Down syndrome has a 50% chance of giving birth to a baby with Down syndrome.  When a woman with Down syndrome produces egg cells during meiosis, half of her eggs will have an extra 21 chromosome. Thus, if fertilization occurs there is a 50% chance that her fertilized egg will contain an extra chromosome 21.  Most cases of Down syndrome result from faulty gamete cell division and are not inherited.  But a small percentage of those with Down syndrome did inherit the chromosomal defect from either their mother or father.  Inheritance symptoms treatment incidence cause testing and screening Children born with Down syndrome vary widely in their symptoms.  The most common symptoms include:  mental retardation, an upward slant to the eyes, decreased muscle tone, flattened facial profile with depressed nasal bridge and small nose, small mouth and abnormal shape to the ears, and laxity around the body’s joints. Down syndrome (DS) is one of the most commonly occurring genetic birth defects, and it is the most common genetic reason for mental retardation.  About 1 in 900 people are born with this disorder.  Because of higher fertility rates in younger women, the majority of DS children are born to mothers under 35 years of age; however, the likelihood of having a child with DS increases with advancing parental age. Prenatal testing can be done to determine if a fetus has Down syndrome (DS).  Babies born with DS usually have physical characteristics that lead to a suspicion of the disorder.  Diagnosis is confirmed with a test called a “karyotype” that gives a complete picture of an individual’s chromosomes.  People with Down syndrome (DS) have an excess, or redundancy, of genetic material in their cells – specifically, an excess of chromosome 21.  The vast majority, approximately 95%, have a complete extra chromosome 21.  Others with DS, 4%, have an extra bit of chromosome 21 attached or “translocated” onto another chromosome — usually chromosome 14.  And some, 1%, have a mixed or “mosaic” pattern of cells in their bodies where some cells have normal amounts of genetic material and other cells have an extra chromosome 21.  There is no cure for Down syndrome (DS) nor are there effective medical treatments at the present time.  However, because of conditions common to those with DS, such as heart defects, hearing deficits, and developmental delays, good medical and supportive care is essential to this population. How is Down syndrome diagnosed? 

Characteristics: Dr. Judith Willner, the Director of Clinical Genetics at Mount Sinai School of Medicine in New York, discusses the typical characteristics of those born with Down syndrome (DS). Intelligence quotients: Dr. Willner talks about intelligence quotients and mental retardation in people with Down syndrome. Genetic Counselors: Ms Zinberg, Director of Genetic Counseling at Mount Sinai School of Medicine in New York, discusses the role genetic counselors play in helping families understand and cope with Down syndrome. Prenatal Testing for DS: Ms Zinberg talks about chorionic villus sampling (CVS) and amniocentesis procedures as ways to diagnose DS in a fetus. Risks of Prenatal Testing: Ms Zinberg talks about risk of spontaneous abortion associated with chorionic villus sampling and amniocentesis. CVS vs. Amniocentesis Ms Zinberg discusses women’s choices in determining which prenatal test is best for them. (CVS is typically performed between 8 and 12 weeks of gestation; amniocentesis, between 12 and 20 weeks.) New DS Prenatal Test: Dr. Willner discusses a new testing technique being studied that is less invasive and can be done early in the pregnancy. How is down syndrome treated? Treatment Dr. Judith Willner, the Director of Clinical Genetics at Mount Sinai School of medicine in New York, discusses treatment options for those with Down syndrome (DS). Monitoring Dr. Willner talks about the importance of monitoring those with DS for specific health problems. Hypothyroidism Dr. Willner talks about hypothyoidism in people with Down syndrome. Alzheimer an DS Dr. Willner explains why those with Down syndrome are at increased risk for developing Alzheimer disease. Theory Dr. Willner puts forth a theory as to why older women are more likely to carry a DS pregnancy to term. What is it like to have Down syndrome? Diagnosis: Jim and Sheila McHale share their feelings and experiences upon learning that their first child had Down syndrome. Child with DS The McHales discuss the evolution of their feelings in raising a child with Down syndrome. Telling Others Jim McHale explains his sensitivity to others’ reactions upon learning that three of his children have Down syndrome. Adoption The McHales talk about the youngest of their two adopted children with Down syndrome, Kate. The Future Jim and Sheila McHale discuss the future of their children with DS. Everyone’s Own Life The McHales talk about all their children and how each should live their own life. School The McHales share their thoughts on whether or not to mainstream children with DS into traditional classrooms. Group Home Jeanne McHale is the oldest daughter of Jim and Sheila McHale. She and her father discuss her transition to the group home setting and some of her experiences there. Boyfriend Jeanne McHale and her father talk about Jeanne’s boyfriend. Family Trip Kate McHale is one of two children with DS that Jim and Sheila McHale adopted. She and her mother recall their trip to Disney World. Sexuality Sheila McHale discusses the sexuality of her children with DS and her oldest daughter’s male friendships. Jeanne McHale has a long-time boyfriend, Peter.