Down syndrome

 What are the causes of Down syndrome?

Down syndrome is caused by a random error in the division of cells that results in the presence of an extra copy of chromosome 21.

This type of error is called non-disjunction. Usually, when a cell divides into two, the pairs of chromosomes are separated so that one chromosome goes to one cell and the other to the other cell. In non-disjunction, an error occurs and both chromosomes of the pair go to the same cell and the other cell does not receive any chromosome of that pair.

Most of the time, this occurs because of a random error during the formation of the egg or sperm. To date, there is no known environmental or behavioral factor for parents known to cause Down syndrome.1,2

After extensive research on these errors in the division of cells, the researchers discovered that:
 In more than 90% of cases, the extra copy of chromosome 21 comes from the mother's egg.
In about 4% of cases it is the father who provides the extra copy of chromosome 21 through the sperm.
    In the rest of the cases, the error occurs after fertilization, while the embryo grows.

Chromosomal changes that can cause Down syndrome

Studies show that there are three types of chromosomal changes that can cause Down syndrome.

    Complete Trisomy 21 In this case, an error during the formation of the ovum or sperm causes one of the two to have an extra chromosome. Therefore, after the egg and sperm come together, the resulting cells will also have three copies of chromosome 21. The complete copy of extra chromosome 21 is found in all the cells of that person - that is, there is a complete trisomy . Complete trisomy 21 is the cause of approximately 95% of Down syndrome cases.1,2,3
    Trisomy 21 mosaic. The cells of the body are not exactly the same. In about 1% of cases of Down syndrome, most of the cells in the body have the extra chromosome, but some do not. This is called "mosaicism." Trisomy 21 mosaic occurs when the error in cell division occurs at an early stage of development but after the union between a normal egg and sperm. It can also occur during an early stage of development when some cells lose an extra chromosome 21 that was present at the time of conception. The symptoms of a person with mosaic trisomy 21 may be different from those of people with complete trisomy 21 or trisomy 21 by translocation, depending on the number of cells in which there is an extra chromosome.1,2
    Trisomy 21 by translocation. In this type of chromosome change, the cells have only a part of the extra copy of chromosome 21. The extra part of the chromosome "sticks" to another chromosome and is transmitted to other cells as the cells divide. This type of change causes approximately 4% of cases of Down syndrome. People with trisomy 21 by translocation do not have specific cognitive or medical characteristics that differentiate them from people with complete trisomy 21.

    Sometimes, a parent who does not have Down syndrome can be a carrier of a translocation on chromosome 21 that can transmit to their children and cause Down syndrome. Studying the chromosomes of the parents allows us to know if this is the cause of the syndrome. A genetic counselor could help families affected by trisomy 21 by translocation to understand the risk of transmitting the syndrome in future pregnancies.1,2,3 .

How do doctors diagnose Down syndrome?

Health professionals can detect the presence of Down syndrome during pregnancy or after the birth of the baby. There are two types of tests to detect Down syndrome during pregnancy:

    Prenatal screening test. This test may show that there is a greater chance that the fetus has Down syndrome, but it can not be determined for sure. If this test indicates a greater probability, the health professional could indicate that a diagnostic test is performed.
    Prenatal diagnostic test. This test can accurately determine the presence of Down syndrome. Diagnostic tests carry a slightly higher risk to the fetus than screening tests.

The American College of Obstetricians and Gynecologists (ACOG) again recommends that all pregnant women be offered screening for Down syndrome.1

Down syndrome prenatal screening test

There are several options for screening for Down syndrome. These are:

    A blood test and an ultrasound test during the first trimester of pregnancy. This is the most accepted detection approach during the first trimester. The blood test allows the health professional to detect the presence of "markers," such as certain proteins, in the mother's blood that might suggest a greater likelihood of the baby having Down syndrome.2 Then the professional of health performs an ultrasound test that uses high-frequency sound waves, to obtain images of the fetus. Ultrasound can detect fluid in the nape of the fetus, which sometimes indicates the presence of Down syndrome. This ultrasound test is called nuchal translucency. During the first quarter, this combined method is more efficient in terms of detection rates than the methods used during the second quarter.3
    Blood tests during the second trimester of pregnancy. As in the first trimester, a blood test allows the health professional to detect the presence of markers in the mother's blood. The triple screening test analyzes the levels of three different markers; The quadruple screening test analyzes the levels of four different markers.3,4
    Combined test (sometimes called integrated test). This approach uses a blood test and an ultrasound test during the first trimester along with a blood test in the second trimester. Health professionals then combine all the results to obtain a risk score for Down syndrome.2

If a woman is pregnant with twins or triplets, the blood test will not be as reliable because the substances of a fetus with Down syndrome would be more difficult to detect.2,3

Prenatal diagnosis test of Down syndrome

If the screening test shows a high probability that a fetus has Down syndrome, a diagnostic test may be performed. The ACOG recommends that pregnant women of all ages have the option to skip the screening test and get a diagnostic test directly. Until recently, this option was only offered to women over 35 and other high-risk women, since the diagnostic test carries a slight risk of miscarriage.1 Before a diagnostic test is performed, the pregnant woman and Your family may want to meet with a genetic counselor to discuss family history and the risks and benefits of having such a test in your specific situation.

The diagnostic test for Down syndrome involves obtaining a sample of genetic material. After the extraction, the sample is analyzed to check for extra material from chromosome 21, which could indicate that the fetus has Down syndrome. Usually, parents will receive test results one or two weeks later. The following procedures are used to obtain the samples.

    Amniocentesis. A health professional extracts a sample of amniotic fluid, which is then analyzed to rule out the presence of the extra chromosome. This test can not be done until weeks 14 to 18 of pregnancy.
    Chorionic villus sampling (CVS for its acronym in English). A health professional removes a sample of cells from a part of the placenta, the organ that connects the mother to the fetus and then analyzes the sample to rule out the presence of the extra chromosome. This test is performed between weeks 9 and 11 of pregnancy.
    Percutaneous umbilical cord blood sample (PUBS). A health professional removes a sample of fetal blood in the umbilical cord through the uterus. Then, the blood is analyzed to rule out the presence of the extra chromosome. The PUBS is the most accurate diagnostic method and allows confirming the results of CVS or amniocentesis. However, PUBS can not be performed until later in pregnancy, between weeks 18 and 22.5

Tests and in vitro fertilization

Another diagnostic approach is used in conjunction with in vitro fertilization. Preimplantation Genetic Diagnosis (PGD) allows doctors to detect chromosomal imbalances and other genetic diseases in the fertilized egg before implanting it into the uterus.

This technique is useful in particular for couples who are at risk of transmitting certain genetic diseases to their children, including disorders associated with the X chromosome, as well as for couples who have suffered repeated spontaneous abortions, subfertile couples or at risk of having disorders of one's own. only gene.

Couples interested in the PDG should consult a genetic counselor and closely monitor the pregnancy, as well as perform additional tests during pregnancy, since they are at higher risk of suffering chromosomal abnormalities after the process of in vitro fertilization.

Diagnosis of Down syndrome after birth

The diagnosis of Down syndrome after birth is usually based, in the first instance, on the physical signs of the syndrome.

But since individuals with Down syndrome may not have these symptoms and many of these symptoms are common in the general population, the health professional will take a sample of the baby's blood to confirm the diagnosis. The blood sample is analyzed to determine the number of chromosomes of the baby.11