Down Syndrome and Edwards Syndrome Genetic Test Improved

Edwards syndrome chromosome
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Pregnant women who are concerned about having a child with Down syndrome or Edwards syndrome can undergo genetic testing, but current screening tests can produce some uncertain results. Now a new genetic test for these chromosomal disorders is nearly 100% accurate.

Current genetic screening tests need improvement

Although any woman can give birth to a child who has chromosomal abnormalities, the risk increases significantly as the age of the mother increases. For example, the chance of carrying a baby with Down syndrome is about 1 in 1,295 in women at age 20 but rises to about 1 in 82 at age 40.

Chromosomal abnormalities are biological errors that occur during the early stages of cell division. In some cases, instead of the normal 23 matched pairs of chromosomes, some infants develop with 22 pairs plus a set of three, which is called trisomy.

Chromosomal abnormalities are also referred to by their trisomy number; for example, Down syndrome is trisomy 21 because the infant has an extra copy of chromosome 21. Edwards syndrome (the condition that affects former presidential candidate Rick Santorum's daughter) is also known as trisomy 18, while Patau syndrome is known as trisomy 13.

New screening test
A new screening test called Digital Analysis of Selected Regions (DANSR) was evaluated in 4,002 pregnant women (average age, 34.3 years) from the United States, Sweden, and the Netherlands. Blood samples were collected and analyzed from all the women, and 3,080 samples were included in the study.

The new genetic test works by analyzing small DNA fragments (cell-free DNA, or cfDNA) found in the mother's blood. Unlike similar tests that evaluate DNA from the entire genome, DANSR focuses on the specific chromosomes under investigation, which makes for a more efficient and less costly test.

Results from the DANSR were than evaluated with a special procedure (algorithm) called Fetal-fraction Optimized Risk of Trisomy Evaluation (FORTE), which accounts for age-related risks and the percentage of DNA from the fetus in the sample to come up with an individualized risk for trisomy detection.

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Using the new genetic test and FORTE, the investigators observed the following:

  • 100% of the 81 trisomy 21 cases were identified as high risk
  • One false positive was found among the 2,888 normal cases, which equals a false-positive rate of 0.03%, compared with false-positive rates of 2 to 3% using currently available screening tests
  • Of the 38 trisomy 18 cases, 37 were identified as high risk
  • Two false positives were found among the 2,888 normal cases, which yielded a sensitivity of 97.4% and a false-positive rate of 0.07%

Down syndrome and Edwards syndrome
One in every 691 babies in the United States is born with Down syndrome, according to the National Down Syndrome Society. Although the incidence of births of Down syndrome increases with the age of the mother, 80% of children with the disorder are born to women younger than 35 due to higher fertility rates in that age group.

At one time, the life expectancy of people born with Down syndrome was poor--only 25 years as of 1983. However, that has risen significantly to age 60 years.

In 2009, a study from Queen Mary, University of London reported that the number of Down syndrome pregnancies has risen dramatically over the past 20 years. The authors noted that the main reason for the increase is that many women are choosing to delay pregnancy.

Edwards syndrome occurs less often than Down syndrome--about one of every 5,000 births. Women older than 30 are at higher risk for bearing a child with the syndrome, although it can appear in younger women.

About 80% of children affected by Edwards syndrome are female. The majority of children with the syndrome die while in the womb, while infants who survive generally live for only a short time due to the vast number of defects in the brain, heart, kidneys, and stomach associated with the syndrome.

Importance of the new genetic test
The study's lead investigator, Mary E. Norton, MD, director of perinatal research at Lucile Packard Children's Hospital at Stanford University, explained that the DANSR is "a more affordable, scalable approach to cfDNA analysis" than current tests. The improved genetic test for Down syndrome and Edwards syndrome "is potentially suitable as a replacement for current, relatively inefficient aneuploidy screening," concluded Norton.

SOURCES:
National Down Syndrome Society
Norton ME et al. Non-invasive chromosomal evaluation (NICE) study: results of a multicenter, prospective, cohort study for detection of fetal trisomy 21 and trisomy 18. American Journal of Obstetrics & Gynecology 2012 June: doi:10.1016/j.ajog.2012.05.021

Image: Wikimedia Commons

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