How Down Syndrome Is Diagnosed

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Down syndrome (trisomy 21) can be diagnosed almost as soon as a baby is born, based on distinctive physical characteristics that prompt immediate testing to confirm the suspicion. Down syndrome can also be diagnosed, or at least suspected, based on any of several prenatal tests including a nuchal translucency screening, sonogram, quadruple screen, or other blood tests. Here is how Down syndrome is diagnosed in both scenarios.

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Imaging

Modern imaging techniques can provide very detailed pictures of what's going on inside of the body, including features of a still-developing fetus. Since many characteristics of Down syndrome are visible, it's possible to pick up on some of them in an ultrasound before a baby is born.

While imaging tests can help indicate the possibility of Down syndrome, they cannot confirm it. Likewise, a negative test does not rule out Down syndrome.

Nuchal Translucency Ultrasound Screening

This specialized ultrasound, which is performed at 11 to 13 weeks, measures the thickness of an area of tissue at the back of a fetus's neck called the nuchal fold. Though this test is recommended for all pregnant women, this is a difficult measurement to obtain and only someone who has been specifically trained and certified to perform this screening can do it.

In general, a measurement under 3 millimeters (mm) is considered normal (or screen negative) and one that's over 3 mm is considered abnormal (or screen positive). In the latter case, it will be important to meet with a genetic counselor to discuss your screening results, what they mean, and your diagnostic testing options such as chorionic villi sampling (CVS) or amniocentesis (see below).

Ultrasound (Sonogram) Screening

Ultrasounds work by using sound waves to generate an image of the fetus. These waves pose no risk to mother or baby. The standard ultrasound is done between 18 and 22 weeks of pregnancy and can reveal a variety of physical characteristics that are associated with an increased risk that a developing baby has Down syndrome. 

The doctor will rub a special gel on your abdomen and then slide a transducer, a wand-like apparatus that transmits sound waves into your abdomen, over your belly. The sound waves travel through the amniotic fluid, deflecting off of structures located in the uterus. The speed at which the waves bounce back differs depending on the density of what they hit. A computer turns this information into an image of the fetus. The harder or denser a structure is, the brighter it will show up on the monitor.

Occasionally, but not always, infants with Down syndrome show subtle signs, called soft markers, on an ultrasound that suggest they may have Down syndrome:

  • A shorter-than-normal femur (thigh) bone
  • A missing nose bone in the first trimester
  • Duodenal atresia: This abnormality of the duodenum, a part of the small intestine, will show up on an ultrasound as a double bubble caused by extra fluid and swelling in the duodenum and stomach. Duodenal atresia sometimes may be detected as early as 18 to 20 weeks, but usually isn't seen until after 24 weeks. Another sign of duodenal atresia in pregnancy is excessive amniotic fluid. If a duodenal atresia shows up in an ultrasound, there is a 30 percent chance that the baby will have Down syndrome.
  • Certain heart defects
  • Gastrointestinal blockages 

These signs do not mean that a baby has Down syndrome for sure. Again, further testing is needed to confirm the diagnosis.

Likewise, it is important to note that most fetuses with Down syndrome show no abnormalities on ultrasound, which can be falsely reassuring to parents who are especially concerned about this disorder.

Maternal Blood Tests

It's important to know that blood tests are used for screening and, like imaging tests for the condition, only indicate the level of possibility that a child has Down syndrome.

Negative screening results mean that your chance of having a baby with Down syndrome is low, but they do not guarantee there are no birth defects. If you have a negative result, you likely will not be offered follow-up diagnostic testing. 

Positive screening results mean the chances a fetus has Down syndrome are higher than normal, and so follow-up diagnostic testing will be offered. That said, most women with screen positive results will have normal healthy babies.

Quadruple Screen

This maternal blood test, which is part of routine prenatal care for all expectant moms, typically is performed between the 15th and 18th weeks of pregnancy. It measures levels of four specific substances. Two of these happen to be associated with Down syndrome:

  • HCG (human chorionic gonadotropin): HCG is a hormone made by the placenta. In fact, very early in pregnancy, it's the substance used to detect pregnancy in home pregnancy tests, since it also shows up in urine. HCG levels in the blood of women carrying babies with Down syndrome tend to be higher than average.
  • PAPP-A (pregnancy-associated plasma protein A): A woman with a low blood level of PAPP-A has an increased chance that her baby will have Down syndrome. Low levels of PAPP-A also may indicate an increased risk for intrauterine growth restriction, premature delivery, preeclampsia, and stillbirth.

Prenatal Cell-Free DNA Screening (cfDNA)

This relatively new test, which extracts DNA from both a mother and fetus using a sample of the mother's blood and screens for chromosome problems such as Down syndrome (as well as trisomy 13 and trisomy 18. It can be done as early in pregnancy as 10 weeks, but is not routinely done.

According to the American College of Obstetricians and Gynecologists(ACOG), doctors will recommend cfDNA only for women with certain risk factors for fetal defects, including advanced maternal age (35 or over); a fetal ultrasound that shows an increased risk of chromosome abnormality; a previous pregnancy with a trisomy; a positive first- or second-trimester maternal screening test; or a known balanced chromosome translocation in the mother or father.

It's important to understand that cfDNA testing can only indicate if a fetus is at an increased risk for a chromosome problem or is unlikely to have one. It is not a diagnostic test. It also is expensive, although the test may be covered by health insurance for women of advanced maternal age.

While these screenings can be helpful, the only way to definitively diagnose Down syndrome is to get a diagnostic test.

Diagnostic Tests

If a prenatal screening test indicates there's a possibility your child will have Down syndrome or if you have risk factors for having a child with the disorder, then you may be faced with taking the next step and confirming the diagnosis. This is an extremely personal decision, one that's fraught with dueling emotional and practical implications.

Deciding Whether to Have a Confirming Test

It can be helpful to ask yourself very specific questions about whether prenatal testing to confirm a diagnosis of Down syndrome (or any birth defect) is the right thing for you and your family. For instance, you'll want to consider your own personality: Do you handle things better when you know what to expect? Or would knowing you're carrying a child with trisomy 21 cause you overwhelming anxiety?

In pragmatic terms, would knowing ahead of time allow you to prepare for the potential health problems your baby with Down syndrome may be born with? And, as difficult as this scenario is to think about, would learning you have a child with a birth defect cause you to consider terminating the pregnancy?

Be open about your thoughts when speaking with your doctor and know that getting a diagnostic test is entirely your choice.

Karyotyping

If you decide to move forward with diagnostic testing, amniocentesis and chorionic villi sampling will be offered to you. Tissue retrieved with either of these procedures will be karyotyped.

A karyotype is an analysis of a baby's genetic makeup that looks at the number of chromosomes he or she has under a microscope.

Under normal circumstances, there are 46 chromosomes organized in 23 pairs. Chromosome pairs are numbered one through 23. In the case of Down syndrome, there is an extra chromosome in the 21st spot, meaning there are three of this particular chromosome. (This is why the clinical name for Down syndrome is trisomy 21.)

A karyotype can be done using almost any type of cell. When a diagnosis is being confirmed after birth, for example, the cells usually are taken from a sample of the baby's blood. During pregnancy, karyotyping can be done by performing one of the following tests. Neither of these is considered a routine part of prenatal care, although they often are recommended for women who are 35 or over or who have other risk factors for having a child with a chromosomal abnormality.

  • Amniocentesis: This test, which is done between weeks 15 and 20 of pregnancy, creates a karyotype using a sample of amniotic fluid. A doctor uses an ultrasound to help guide a long, thin needle into a woman's abdomen and through to the uterus in order to extract a sample of fluid from the amniotic sac. This fluid contains skin cells that have sloughed off of the fetus, which will then be tested.
    • It takes just a few moments to extract amniotic fluid, but most women do report feeling some discomfort and mild cramping. Amniocentesis is relatively safe: It carries a one-in-400 risk of causing miscarriage. The process of culturing the cells so that they can be karyotyped can take up to two weeks.​
    • According to the National Down Syndrome Society  (NDSS), the test is nearly 100 percent accurate in diagnosing Down syndrome prenatally. What's more, it can distinguish between complete trisomy 21, translocation Down syndrome, and mosaic Down syndrome.
  • Chorionic Villi Sampling (CVS): As with amnio, CVS testing uses karyotyping to diagnose Down syndrome. However, the cells examined are taken from structures in the placenta called chorionic villi.
    • CVS is performed at 11 to 13 weeks of pregnancy and is done in one of two ways: Either a needle is inserted directly into the abdomen or is threaded through the cervix (much like having a Pap smear).
    • The insertion of the needle can be painful, but the procedure is very quick. CVS poses the same small risk of miscarriage as amniocentesis, is nearly 100 percent accurate, and is able to reveal which type of trisomy 21 a baby has. It usually takes a couple of weeks for full results from CVS testing to be finalized.

FISH Testing

Fluorescent in situ hybridization (FISH testing or FISH analysis) is a relatively new technique that can determine how many copies of a particular chromosome a cell has. It's usually done using the same tissue sample from an amniocentesis or CVS test.

To perform a FISH analysis, colored dyes are used to highlight certain chromosomes, which makes it possible to count them. One advantage of using FISH analysis rather than karyotyping is that it isn't necessary to culture cells before analyzing them. This means results can be available in a few days rather than a few weeks.

A disadvantage of FISH is that unlike karyotyping, it only can reveal if there is an extra chromosome 21. It doesn't offer information about the structure of the chromosomes that would be needed to identify Down syndrome as complete, mosaic, or translocation trisomy 21. The differences in these types affect the severity of the condition and the likelihood of conceiving another child with Down syndrome.

Physical Examination

Down syndrome is usually quite evident as soon as a baby with the disorder is born, as many of its distinctive physical characteristics are present at birth. These include:

  • A round face with a flat profile and small facial features (nose, mouth, ears, and eyes)
  • Protruding tongue
  • Almond-shaped upturned eyes with epicanthus folds
  • White flecks in the colored part of the eyes (Brushfield spots)
  • A short neck and a small head that's somewhat flat in the back (brachycephaly)
  • A single crease across the palm of each hand (normally there are two), short stubby fingers, and a pinky finger curves inward—a condition called clinodactyly 
  • Small feet with a larger than normal space between the big and second toes
  • Hypotonia, or low muscle tone, which causes the newborn to appear “floppy” due to a condition called hypotonia.

These characteristics are red flags that a newly born baby has Down syndrome. To confirm the diagnosis, a blood sample will be taken and used to create a karyotype.

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