How Down Syndrome is Diagnosed

A summary of the screening and diagnostic tests you may undergo.

Doctor tending to baby girl with Down Syndrome
JGI/Tom GrillMore

The diagnosis of Down syndrome is usually made in one of two ways—either shortly after birth or during a pregnancy (prenatally). While the diagnostic process can be anxiety-ridden, gaining basic knowledge about what kinds of tests you can expect and how to interpret them can be extremely helpful for you and your partner.

Diagnosing Down Syndrome At Birth

Even with prenatal testing, most infants with Down syndrome are diagnosed shortly after birth.

Most often this is because the physician notices that the baby had some distinctive facial or physical features often seen in Down syndrome.

For example, infants with Down syndrome may have smaller heads than other infants, small upslanting eyes, a somewhat flattened nose, and a small mouth with a protruding tongue. They can also have differences in their hands and feet. They may have a single crease across their palm (called a single palmar crease), small hands with short fingers, and a somewhat larger space between their big and second toes.

Most infants with Down syndrome also have low muscle tone or hypotonia. Occasionally, infants with Down syndrome are born with other more serious birth defects such as heart defects and gastrointestinal defects.

If your physician notices that your child had some of these features, she may become suspicious that the baby has Down syndrome. Your physician will then order a chromosome analysis (also referred to as a karyotype) to confirm the diagnosis.

A chromosome study is a blood test that looks at the baby's chromosomes under a microscope. Most individuals have 46 chromosomes total. People with Down syndrome have an extra number 21 chromosome for a total of 47 chromosomes. 

Diagnosing Down Syndrome Prenatally 

While Down syndrome is often diagnosed shortly after birth, it is also increasingly being diagnosed during pregnancy (prenatally) due to abnormal ultrasound (sonogram) findings, an abnormal result on a blood test done by mom (maternal serum screening test), or by amniocentesis or chorionic villi sampling (CVS) testing.

 Chorionic villi sampling or CVS is a test done on the placenta between 10 and 12 weeks of pregnancy.

Both ultrasound and maternal serum tests are screening tests. In contrast, amniocentesis and CVS are considered diagnostic tests. A screening test can never give you a firm diagnosis—it simply tells you if you have a higher risk to have a baby with Down syndrome. On the other hand, a diagnostic test gives you a firm diagnosis.

Ultrasound Findings in Down Syndrome

An ultrasound, also know as a sonogram, is a test done during pregnancy which uses sound waves to generate a picture or image of the fetus. Occasionally, but not always, infants with Down syndrome show subtle signs on an ultrasound that can make your doctor suspect that the fetus has Down syndrome.

Some of these subtle signs include a decrease in femur length (a bone in the leg), an increase in the skin behind the neck (called nuchal translucency), or absence of the nose bone. These are what are often referred to as "soft markers" because none of these ultrasound findings will cause the fetus any problems by themselves.

However, they can make the doctor suspicious that the fetus has Down syndrome. Other more serious signs that can also be seen on an ultrasound include heart defects and intestinal blockages.

Down syndrome cannot be diagnosed based on ultrasound findings alone. These findings simply suggest that there is a higher risk that the fetus may have Down syndrome. Based on this increased risk, your doctor will recommend that you consider an amniocentesis or CVS to confirm the diagnosis. It is up to you to decide whether or not to have this testing.

It is important to note that most fetuses with Down syndrome show no abnormalities on ultrasound. Often people are falsely reassured by a normal ultrasound because they believe it means that there are no problems with the baby. Unfortunately, this is simply not true. Having a normal ultrasound is great and is somewhat reassuring, but it is not a guarantee that everything is perfect.

Maternal Serum Screening Tests in Diagnosing Down Syndrome

A blood test (done on mom) often called the "quadruple screen" can be done between the 15th and the 20th week of pregnancy. The quadruple screen looks at four substances in the mother's bloodstream:

AFP is produced in the yolk sac and fetal liver, estriol is produced by the fetus and placenta, hCG is produced within the placenta, and inhibin A is produced by the placenta and ovaries. When a fetus has Down syndrome, the levels of these substances in the mother's bloodstream can be different from normal. 

The quadruple screen is—as its name implies—just a screening test. It cannot tell for sure if your baby has Down syndrome, but it can tell you if your risk is higher. If your screening test is positive, it simply means your risk of having a baby with Down syndrome is higher than other women your age. But even with a positive screening test, most women will have babies without Down syndrome. Conversely, a negative quadruple screen means that the chance of Down syndrome is low but not zero. It doesn't guarantee a baby without Down syndrome.

The quadruple test combined with a woman's age can detect approximately 75 percent of pregnancies affected by trisomy 21 in women younger than 35 years and more than 80 percent of pregnancies in women age 35 and older. 

In the late 1990s, first-trimester screening tests for Downs syndrome (and other chromosomal abnormalities) were developed. These tests entail measuring nuchal translucency with ultrasound and two blood tests: human chorionic gonadotropin and pregnancy-associated plasma protein A (PAPPA). The results of these tests are combined with a woman's age to determine a final risk for chromosomal abnormalities, including trisomy 21. 

Amniocentesis in Diagnosing Down Syndrome

If a screening blood test or an ultrasound shows an increased risk, or if you are over age 35, you will be offered an amniocentesis. An amniocentesis is a test that is usually done between 15 and 20 weeks of pregnancy. It involves using a thin needle inserted through your abdomen (not through your belly button), to obtain some of the amniotic fluid surrounding the fetus. This amniotic fluid contains some of the fetus's skin cells. These skin cells can be used to obtain a fetal karyotype—a picture of the fetus's chromosomes. If the fetus is discovered to have an extra number 21 chromosome, then the diagnosis of Down syndrome is made.

CVS in Diagnosing Down Syndrome

Chorionic villi sampling or CVS is a procedure that is done at about 11 to 13 weeks of pregnancy. In this procedure, a thin needle or  catheter is inserted into the placenta to obtain some cells. The placenta is derived from the same cells that make up the fetus, so by looking at the cells of the placenta, you are also looking at the cells of the fetus. These cells are then sent to the lab for chromosome analysis. If the karyotype reveals that the fetus has an extra number 21 chromosome, then the fetus will have Down syndrome.

Amniocentesis and CVS are optional tests during pregnancy—they are not something that you have to do. It is up to you to decide whether the benefits of knowing about the fetus's chromosomes outweigh the risk of the procedure. Both procedures have a small risk of miscarriage. The risk is less that 1 percent for amniocentesis and about 1 to 2 percent for CVS. Some women prefer CVS to amniocentesis because they want to get information earlier in their pregnancy, and others prefer amniocentesis because of the lower risk of miscarriage. Only you can decide what is best for you.

Sources:

American Pregnancy Association. (2016). Quad Screen Test. 

National Institute of Child Health and Human Development (NICHD). Down Syndrome: Condition Information

Simpson JL. Invasive procedures for prenatal diagnosis: any future left? Best Pract Res Clin Obstet Gynaecol. 2012 Oct;26(5):625-38.

Smith M, Visootsak J. Noninvasive screening tools for Down syndrome: a review. Int J Womens Health. 2013;5:125-31.

Zolotor AJ, Carlough MC. Update on Prenatal Care. Am Fam Physician. 2014 Feb 1;89(3):199-208.

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