Down Syndrome Genetic Testing Basics - Medicine and Health

Down Syndrome

What is Down syndrome?
Down syndrome, a disorder that is present at birth, affects the body's physical and mental development. While no two people with Down syndrome are exactly alike, they do share some common physical features. Babies with Down syndrome have similar facial features, tend to have lower muscle tone, and typically learn to walk and talk slightly later than other children. A person with Down syndrome typically has a slightly small head that is flattened in the back; up-slanted eyes; extra skin folds at the inner corners of the eyes; small ears, nose and mouth; short stature; small hands and feet; and some degree of mental disability.

Normally, a child inherits two copies of chromosome 21 — one from each parent. If a child inherits an extra chromosome 21, the child will have Down syndrome. Because Down syndrome usually affects every cell in the body, people can have a variety of medical problems. For example, about 40% of children with Down syndrome are born with a heart problem. This can range from a very small hole between two heart chambers to a very large hole that requires surgery.

Related Reading
Down Syndrome

How common is Down syndrome?
It occurs in about one of every 800 births. Between 3,000 and 5,000 children with Down syndrome are born each year in the United States.

Who is at risk of having a baby with Down syndrome?
Down syndrome can affect people from any ethnic group. A couple's likelihood of having a baby with Down syndrome increases as the woman gets older. For example, when a woman is 35, Down's occurs in about one of every 200 births. By age 40, Down's occurs in almost one in 100 births. Researchers think older eggs (a woman carries all of her eggs from birth) may have problems sorting out the correct number of chromosomes.

In addition, people have an increased risk if they carry a translocation involving chromosome 21.

Is there a cure?
No, but the medical complications associated with Downs can be treated and managed. Treatment for Down syndrome is specific to an individual's needs. For example, a child or adult may need heart surgery to correct a heart defect. In addition, someone with Downs might need occupational therapy, physical therapy and speech therapy.

The Genes For Down Syndrome

A typical person with Down syndrome has an extra copy of every gene on chromosome 21. This can happen for two reasons:

Unequal Cell Division
An egg begins as a pre-egg cell that has two copies of each chromosome. A pre-egg cell divides into two eggs. Before it divides, the chromosomes are sorted out so that one copy of each chromosome will go into each of the two eggs. When unequal cell division occurs, one egg gets two copies of chromosome 21, and the other egg gets none. When the egg with two copies of chromosome 21 combines with a sperm (which carries one copy of chromosome 21), the baby inherits three copies of the chromosome.

Unequal cell divisions are more likely to occur as a woman ages. (About 10% of the time, the extra chromosome comes from the sperm. This is also due to unequal cell division, but is not clearly related to a man's age.)

Chromosome 21 Translocation
A translocation is a type of chromosomal rearrangement. In one of the parents, for example, one of the two copies of chromosome 21 could break off and combine with another chromosome. All the chromosomes are still present, but in a different order. This parent would have no symptoms of Down syndrome but would be a carrier. The parent could then pass on the remaining, normal chromosome 21 plus the translocated copy, and the other parent would contribute a normal chromosome 21, resulting in a total of three copies of chromosome 21 in the embryo. Therefore, a baby could inherit a regular chromosome 21 from each parent in addition to this rearranged chromosome, resulting in a total of three copies of chromosome 21.

Translocations are not as common, but they increase the risk of having another baby with Down syndrome in a future pregnancy. For that reason, if a baby has Down syndrome caused by a translocation, the parents should have their chromosomes tested.

Should You Be Tested?

Should you have a test for Down syndrome?
Anyone can have a baby with Down syndrome. You might like to know, during the pregnancy, if your baby has Down syndrome. There are two categories of tests:

Screening tests try to identify babies that might have Down syndrome, but these tests cannot tell for sure, they can only tell if your baby is at increased risk of Down syndrome. Screening tests include:

Second trimester (serum) screening (sometimes called a “triple screen” or a “quad screen”) to check for certain substances in the mother's blood
First trimester screening (early ultrasound and serum screening)
Second trimester ultrasound



Diagnostic tests are for women who will be over age 35 at delivery, who received an abnormal result on a screening test, or who are anxious due to a prior pregnancy. Diagnostic tests require a sample of cells from the fetus. Tests include:

Chorionic villus sampling, usually performed between 10 and 12 weeks, involves taking a sample of chorionic villus cells from part of the placenta that contains fetal cells.
Amniocentesis, usually performed after 15 weeks, requires the removal of fetal cells from the amniotic fluid that surrounds the baby.

In both cases, the cells are sent to a lab for analysis.

If you have had a child born with Down syndrome, it is important to have your child's chromosomes checked before starting another pregnancy. If you carry a translocation, you have a higher risk of having another child with Down syndrome.

Be sure to talk with your obstetrician or a genetic counselor about your options.

Understanding Test Results and Options

How Do You Make Sense Of The Results?

If my serum screen test or my ultrasound screening test shows an increased risk for Down syndrome, what does that mean for my pregnancy?
It does not mean that your baby will definitely have Down syndrome. You can only confirm whether your child has Down syndrome by receiving one of the diagnostic tests. Talk to your obstetrician or a genetic counselor. They can help you decide whether to pursue a diagnostic test.

Does anyone ever get a positive screening test result and then not have a baby with Down syndrome (a false positive)?
Yes. The serum screen test only indicates that your child will have an increased risk of having Down syndrome. The test produces false positives in 3% to 7% of cases. The early ultrasound can also show false positives. The later ultrasound may frequently show some of the Down syndrome markers in babies without the extra chromosome. Of the three screening tests, the later ultrasound has the highest chance for a false positive.

Does anyone ever get a negative screening test and then have a baby with Down syndrome (a false negative)?
Screening tests are never perfect. The second trimester serum screen and first trimester screening test (early ultrasound with serum screen) detects Down syndrome accurately about 60% to 80% of the time. But if you would like to know for sure, you need a diagnostic test.

Does anyone ever get a positive chromosome analysis and then not have a baby with Down syndrome (a false positive)?
If a baby has an extra chromosome 21 as a fetus, the baby will have Down syndrome.

Rarely, chorionic villus sampling will show an extra chromosome 21 for a baby that does not have Down syndrome. This is a phenomenon called "confined placental mosaicism." Mosaicism means not all the cells of the baby and placenta are the same. The way to figure out if this happened is to have an amniocentesis or periumbilical blood sampling after the chorionic villus sampling to make sure that the cells being tested came from the baby. If the amniocentesis also shows the extra chromosome 21, then your baby will have Down syndrome.

An amniocentesis can verify the results. If the amniocentesis also shows the extra chromosome 21, then your baby will have Down syndrome.

Does anyone ever get a negative chromosome analysis and then have a baby with Down syndrome (a false negative)?
Chromosome analysis detects Down syndrome in more than 99% of cases. While rare, a false negative is possible because a baby can have an extra copy of chromosome 21 in only some cells. That baby would have normal cells and Down syndrome cells. If the chromosome analysis only looks at the normal cells, you could get a false negative.

My doctor said the ultrasound test showed the baby might have Down syndrome. What does that mean?
The ultrasound may show that your child has some of the physical features typical of babies with Down syndrome. Yet, many babies without the disease may have these features. If the ultrasound detects physical features related to Down syndrome in your child, talk to your physician about getting chromosome analysis to confirm the diagnosis.

Personal Questions

My screening test indicates my baby might have Down syndrome. Why should I get an amniocentesis if I'm going to continue the pregnancy no matter what?
A screening test (such as the serum screen or ultrasound) only indicates the increased risk your child has for Down syndrome. If you want to know for sure, you need to receive a diagnostic test (such as amniocentesis). Some couples get tested to lessen their anxiety throughout the rest of the pregnancy. Some couples get tested to help them prepare for the potential birth of a child with Down syndrome. Preparation may include seeking the most suitable hospital for a safe delivery and emotional support.

If I have the Down syndrome translocation, can I have children who don't have Down syndrome?
Yes, depending on which type of translocation you have. One type of translocation makes it so a person can only have children with Down syndrome. With the more common type of translocation, it is possible to have children who do not have Down syndrome. Your risk of having a child with Down syndrome, however, is higher than it is for other people. Further, your children who do not have Down syndrome will fall into two categories — those who carry your same translocation and those who do not. This becomes important if your child decides to start a family.

It is unlikely that both a mother and father would both carry a chromosome 21 translocation. But, if they did, they would have a much higher risk of having a child with Down syndrome.

If I DON'T have the Down syndrome translocation, can I have children who have Down syndrome?
Anyone can have a baby with Down syndrome. If you have a translocation, then your risk is much higher than other people. If you do not have a translocation, then the risk you have, as a couple, depends on the age of the mother.

Is there any harm in finding out if I carry the translocation?
Carrying the translocation for Down syndrome has no known health implications.

If one of my family members has a child with Down syndrome, does that increase my risk?
It depends. If the child does not have a translocation, then your risk is more related to your age at the time of delivery. Consider the example that your sister has a child with Down syndrome. If your sister's child did not have a translocation, then your risk of having a baby with Down syndrome is only related to your age. If your sister's child has Down syndrome caused by a translocation, then you might also carry that translocation. You would need to have your chromosomes examined to know for sure.

Test Details

How do the tests work?
To discover whether your unborn child has inherited Down syndrome, you and your partner can seek prenatal testing. There are two types of tests — screening tests, which identify a fetus that might have Down syndrome, and diagnostic tests, which tell you if the fetus actually does have Down syndrome.

Screening Tests

Second trimester serum screening. This blood test checks the levels of three or four chemicals in the mother's blood during pregnancy weeks 16 to 18. The chemicals are: maternal serum human chorionic gonadotropin (MS-HCG), unconjugated estriol (uE3-estriol), maternal serum alpha-fetoprotein (MS-AFP) and inhibin A (some labs do not test inhibin A). An increase in MS-HCG and inhibin A along with a decrease in the other two markers indicates an increased risk of Down syndrome. The American College of Obstetrics and Gynecology recommends that women under age 35 receive the serum screen test for Down syndrome during their pregnancy.
First trimester screening. This test combines an early ultrasound to measure the thickness of skin at the back of the baby's neck in addition to measuring two markers in the mother’s blood: the free beta subunit of human chorionic gonadotropin ( free beta-hCG), and pregnancy-associated plasma protein-A (PAPP-A). Although this screening test is newer than the second trimester serum screen, it appears to be as effective. A woman can receive an early ultrasound between weeks 11 and 14. Note: because the test requires special ultrasound training, it is not available in all hospitals.
Later ultrasound. This test, routinely performed on all pregnancies at 16 to 20 weeks, involves a detailed survey of the fetal anatomy. This ultrasound is not done specifically to look for Down syndrome, but it may detect features associated with the disorder.

Diagnostic Tests

Chorionic villus sampling. This test collects a small sample of cells from the placenta at the base of the umbilical cord. This is done using a thin needle and ultrasound guidance.
Amniocentesis. This test takes a sample of fluid from around the fetus (without touching the fetus). This fluid contains fetal skin cells.

Both diagnostic tests produce cells containing the fetal chromosomes. These are examined for abnormalities in a lab.

What are the costs of the tests?
The serum screen tests cost about $300 to $400 and the chromosome analysis costs about $1000. Costs for chorionic villus sampling, amniocentesis and ultrasounds vary depending upon the physician and the hospital.

Does insurance pay for the test?
Most health insurance companies pay 80% or more of the cost of these tests. Some plans pay all of the cost, while others won't pay any portion. If you are considering any of these tests, call your insurance company and ask about its coverage.

How long does it take to get results?
Serum screen results take a few days. Ultrasound results are shared on the same day. Chorionic villus sampling and amniocentesis take about two weeks. (Results of these two tests are reported to the medical center that ordered the test. You would then return to the center for another appointment to discuss the results.)

Can a health insurance company raise my rates or drop me from coverage if I have a baby with Down syndrome?
Not usually, although this may depend on whether or not you have group insurance or are self-employed. The Federal Health Insurance Portability and Accountability Act (HIPAA) of 1996 prohibits health insurance discrimination based on any "health status-related factor," (including genetic information) by group health plans. People with group insurance are usually covered by HIPAA, while people who are self-employed are only covered by state laws.

Some states have enacted legislation to cover the gaps. Thirty-four states prohibit health insurance companies from using genetic information to deny coverage. Other states require specific justification for the use of genetic information in denying a claim.