Causes of Down Syndrome

Mother and daughter with down syndrome
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What are the causes of Down Syndrome? Are there different types? Is there anything to do to lower the risk you will have a child with Down Syndrome? Can you predict your risk based on your age? These are just a few of the questions parents-to-be and others ask.

What Is Down Syndrome?

Down syndrome refers to certain characteristics that occur in children and adults who have an abnormal number of number 21 chromosomes.

As humans, we have 46 chromosomes or 23 pairs of chromosomes. 22 pairs are considered autosomes, and the other pair are the sex chromosomes—either XY for a boy and XX for a girl.

Down syndrome—trisomy 21—occurs when there are 3 rather than 2 number 21 chromosomes (hence, trisomy 21).

Understanding the Genetics 

The most common type of Down syndrome—complete trisomy 21—occurs as a result of a process called nondisjunction. When a cell divides, one of each pair of chromosomes goes to each daughter cell. With a nondisjunction, the two chromosomes of a pair do not split properly which results in 2 copies of the chromosome going to one cell and no copies going to the other cell. The cell which receives 2 copies of the 21st chromosome is responsible for Down's syndrome.

Most of the time trisomies (3 copies of chromosomes) are not compatible with life. In adults, trisomy 21 results in Down syndrome.

There are other trisomies as well. Babies with trisomy 18, Edwards syndrome, may now sometimes survive childhood. Klinefelter's syndrome (47 XXY) occurs in 1 in 500 babies.


To better understand the genetics of Down syndrome it's important to first define the different types.

Complete Trisomy 21 - Complete trisomy 21 occurs as described above, via a process called nondisjunction.

Translocation Down syndrome or Translocation Trisomy 21 -The process of translocation Down syndrome often begins prior to conception of the parent of a child with this type of Down syndrome.

In a translocation, part of one chromosome breaks off and becomes attached to another chromosome during meiosis—the process of cell division that takes place in the formation of eggs and sperm. This process results in 3 copies of chromosome 21, but one copy is attached to another chromosome, often chromosome 14. In other words, the baby (the parent that is) ends up with 45 chromosomes, but lives and functions normally because all of the genetic material required on the 21st chromosome is still present. These parents with "balanced" translocations do not have any characteristics of Down syndrome.

When these parents have children, however, the babies end up with 3 copies of chromosome 21, but unlike nondisjunction trisomy, the extra chromosome is attached to another chromosome. Learn more about translocations.

Mosaic Down Syndrome - Mosaic Down syndrome is the least common form of Down syndrome and occurs as the result of genetic changes which take place after fertilization. In children with mosaic Down syndrome, not all cells have 3 copies of chromosome 21.

The symptoms that a child has will depend on the percent of cells in the body which have the extra chromosome.

How Trisomy 21 Occurs

As noted above, trisomy 21 can occur through the processes of nondisjunction or translocation during cell division. No one is certain why these "accidents" in cell division occur, and in fact, considering the vast number of cell divisions that take place from the formation of the gametes (sperm and eggs) to a newborn baby, it is surprising this does not happen more frequently.

In nondisjunction, for around 90% of children, the extra chromosome comes from the mother (the egg).

Roughly 4% of the time it comes from the father (the sperm) and the rest of the time it occurs after fertilization.

Risk Factors 

The only known risk factors for Down syndrome at this time include:

  • Increasing maternal age
  • Having a previous child with Down syndrome
  • Having a family history of Down syndrome

It's important to note that the second two risk factors are risk factors only for translocation trisomy 21, and are therefore risk factors for less than 5% of cases of Down syndrome.

It's also important to note that there are not any environmental (such as toxins, carcinogens, etc.) or behavioral factors that are linked to the development of Down syndrome. Other than increasing with maternal age, it appears to occur randomly.

Maternal Age

The incidence of Down syndrome clearly increases with maternal age, though it's important to realize that roughly 80% of children with Down syndrome are born to women who are younger than 35 years of age.

The risk of Down syndrome with age is:

  • Age 25 - 1 in 1,200
  • Age 30 - 1 in 900
  • Age 35 - 1 in 350
  • Age 40 - 1 in 100
  • Age 45 - 1 in 30
  • Age 49 - 1 in 10

Increased Risk With Future Births

If parents have a child with Down syndrome, this risk of having another child with Down syndrome is 1 in 100. Yet depending upon the type of Down syndrome this risk may be higher or lower.

When a baby has translocation Down syndrome, genetic counseling may help determine if the mother, father, or neither are carriers and therefore the risk in future pregnancies.

Is It Inherited?

Only one type of Down syndrome—translocation Down syndrome—is considered inheritable. Since this type of Down syndrome accounts for only around 4% of cases of Down syndrome, and then, only 1/3 rd of these children are thought to have inherited the translocation, only around 1% of Down syndrome is currently "hereditary."

For parents of a child with Down syndrome due to a translocation, there may be an increased likelihood of Down syndrome in future pregnancies. This is because one of the 2 parents may be a balanced carrier of the translocation. Sometimes neither parent of a child with translocation trisomy 21 is a balanced carrier, and in such a situation there is not an increased risk for Down syndrome in future pregnancies.  With regard to genetic counseling, it is also important that parents of a child with translocation know that their other children could be carriers of the balanced translocation, and themselves could be at risk of having a baby with Down syndrome in the future.

Prenatal Testing

Many obstetricians recommend that women who become pregnant at age 35 or older undergo prenatal testing for Down syndrome. This is a very personal decision and is only a guideline. Couples can choose to undergo testing at a younger age or forego testing at an older age.

Genetic Counseling

Depending on the tests being considered, and personal and family history of medical conditions, some couples choose to go through genetic counseling.  This is advantageous in a few ways

  • Maternal age alone will not predict roughly 80% of births of babies with Down syndrome, on one hand, and there can be other pregnancy risks in women over age 35.
  • There are other genetic disorders, such as sex chromosome abnormalities that can be found on some, but not other, tests ordinarily done for Down syndrome.
  • Some genetic disorders run in families for which we do not have testing.

Another important question to ask before testing is why you would want to know if your child had Down syndrome. Would you do anything differently? Do you think it would help you prepare for the future? A genetic counselor can help you ask these questions and make choices that are best for you with regard to testing.

Testing Options

There are several testing options available for Down syndrome, each done at a different time of pregnancy, and having a different degree of sensitivity, specificity, and false positives (medical terms that basically mean the ability to pick up something without frightening parents for no reason.) Some of the tests available include:

  • Serum alpha-fetoprotein testing - Learn about the controversies of alpha-fetoprotein, triple, quad, or penta screening.
  • Ultrasound testing - Nuchal fold testing for down syndrome is usually done between 11 and 14 weeks.
  • Amniocentesis - Amniocentesis for Down syndrome is usually done between 15 and 20 weeks.
  • Chorionic villus sampling - Chornionic villus sampling is usually done between 10 and 12 weeks.

Bottom Line

If you are a parent thinking about testing for Down syndrome, this can be a very anxious time. There is nothing more important to us than the health and happiness of our children and future children. Considering this, consider one thought before you go.

If you had a child with Down syndrome, would that child be happy? Certainly, especially with some of the associated medical problems, having a child with Down syndrome can be difficult for parents. That goes without saying. But can you see the smiles? How often do you see children (and adults) with Down syndrome smiling? Most of you will say "often." Now think about some children and adults of high intelligence who are very highly functioning. Do you see as many smiles?

This comment is certainly not meant to belittle any fears. Those fears are real and important to get out in the open. Yet as parents, we usually say that our greatest hope is that our children will have a "happy" life and that happiness is not always dependent upon having a high IQ, or looking like everyone else. In fact, many children and adults with Down syndrome appear to be able to smile through times that those without the syndrome get caught up with, such as ruminating about things we can't change in the past or worrying about or fearing the future.

In addition, despite medical conditions associated with Down syndrome, nearly 80% of children born with Down syndrome today are expected to reach the age of 60 years.

If you are thinking about screening, or have learned that you may have a child with Down syndrome, take a moment to read this letter to a new parent with a baby with Down syndrome.


National Institute of Child and Human Development. What causes Down syndrome? Updated 01/17/14.