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Down Syndrome

Definition

Down syndrome is a set of cognitive and physical symptoms that result from having an extra chromosome 21 or an extra piece of that chromosome. It is the most common chromosomal cause of mild to moderate intellectual disabilities. People with Down syndrome are at risk for several other health conditions.

Understanding Down syndrome and other intellectual and developmental disabilities is part of the reason NICHD was established. Today, the institute continues to lead research on the causes, progression, treatment, and management of Down syndrome, as well as on conditions and diseases that are associated with the syndrome.

Down syndrome describes a set of cognitive and physical symptoms that result from an extra copy or part of a copy of chromosome 21.

Chromosomes carry the genes that tell the body to develop in certain ways and to perform certain functions. Most cells of the human body contain 23 pairs of chromosomes—one set of chromosomes from each parent—for a total of 46 chromosomes. People with Down syndrome have either a full or a partial extra copy of chromosome 21, for a total of 47 chromosomes. (The syndrome is sometimes called 47,XX,+21 or 47,XY,+21 to indicate the extra chromosome 21.)

The extra chromosome disrupts the normal course of development and results in the physical features and intellectual and developmental disabilities associated with the syndrome.1

The degree of intellectual disability in people with Down syndrome varies but is usually mild to moderate. Generally, children with Down syndrome reach key developmental milestones later than other children. People with the syndrome are also more likely to be born with heart abnormalities, and they are at increased risk for developing hearing and vision problems, Alzheimer’s disease, and other conditions. However, with appropriate support and treatment, many people with Down syndrome lead happy, productive lives. In recent decades, life expectancy for people with Down syndrome has increased dramatically, from 25 years in 1983 to 60 years today.

According to the Centers for Disease Control and Prevention, Black infants with Down syndrome have a lower chance of surviving beyond the first year of life compared with white infants with Down syndrome. More research is needed to help understand why.

Down syndrome is named after John Langdon Down, the first physician to describe the syndrome systematically.

Symptoms

The symptoms of Down syndrome vary from person to person, and people with Down syndrome may have different problems at different times of their lives.

Physical Symptoms

Common physical signs of Down syndrome include:

  • Decreased or poor muscle tone
  • Short neck, with excess skin at the back of the neck
  • Flattened facial profile and nose
  • Small head, ears, and mouth
  • Upward slanting eyes, often with a skin fold that comes out from the upper eyelid and covers the inner corner of the eye
  • White spots on the colored part of the eye (called Brushfield spots)
  • Wide, short hands with short fingers
  • A single, deep crease across the palm of the hand
  • A deep groove between the first and second toes

In addition, physical development in children with Down syndrome is often slower than development in children without Down syndrome. For example, because of poor muscle tone, a child with Down syndrome may be slow to learn to turn over, sit, stand, and walk. Despite these delays, children with Down syndrome can learn to participate in physical exercise activities like other children. It may take children with Down syndrome longer than other children to reach developmental milestones, but they will eventually meet many of these milestones.

Intellectual and Developmental Symptoms

Cognitive impairment, or problems with thinking and learning, is common in people with Down syndrome and usually ranges from mild to moderate. Only rarely is Down syndrome associated with severe cognitive impairment.

Other common cognitive and behavioral problems may include:

  • Short attention span
  • Poor judgment
  • Impulsive behavior
  • Slow learning
  • Delayed language and speech development

Most children with Down syndrome develop the communication skills they need, although it might take longer for them to do so compared with other children. Early, ongoing speech and language interventions to encourage expressive language and improve speech are particularly helpful.

Parents and families of children with Down syndrome can connect with other families and people with Down syndrome from around the world to learn more and share information.

Associated Conditions and Disorders

People with Down syndrome are at increased risk for a range of other health conditions, including autism spectrum disorders, problems with hormones and glands, hearing loss, vision problems, and heart abnormalities.

Causes

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

The type of error is called nondisjunction. Usually, when one cell divides in two, pairs of chromosomes are split so that one of the pair goes to one cell and the other from the pair goes to the other cell. In nondisjunction, something goes wrong and both chromosomes from one pair go into one cell and no chromosomes from that pair go into the other cell.

Most of the time, the error occurs at random during the formation of an egg or sperm. To date, no behavioral activity of the parents or environmental factor is known to cause Down syndrome.

After much research on these cell division errors, researchers know that:

  • In the majority of cases, the extra copy of chromosome 21 comes from the mother through the egg.
  • In a small percentage (less than 5%) of cases, the extra copy of chromosome 21 comes from the father through the sperm.
  • In the remaining cases, the error occurs after fertilization, as the embryo grows.

Types of Down Syndrome

Research shows that three types of chromosomal changes can lead to Down syndrome.

  • Complete trisomy 21. In this case, an error during the formation of the egg or the sperm results in either one having an extra chromosome. So after the egg and sperm unite, the resulting cells will also have three copies of chromosome 21. The complete extra copy of chromosome 21 is in all of the person’s cells—or a complete trisomy. Almost all Down syndrome cases result from complete trisomy 21.
  • Mosaic trisomy 21. Not every cell in the body is exactly the same. In a small percentage (less than 5%) of Down syndrome cases, most of the cells in the body have the extra chromosome, but some of them don’t. This is called “mosaicism.” Mosaic trisomy 21 can occur when the error in cell division takes place early in development but after a normal egg and sperm unite. It can also occur early in development when some cells lose an extra chromosome 21 that was present at conception. The symptoms of someone with mosaic trisomy 21 may vary from those of someone with complete trisomy 21 or translocation trisomy 21, depending on how many cells have the extra chromosome.
  • Translocation trisomy 21. In this type of chromosomal change, only part of an extra copy of chromosome 21 is in the cells. The extra part of the chromosome gets “stuck” to another chromosome and gets transmitted into other cells as the cells divide. This type of change causes a small number of Down syndrome cases. There are no distinct cognitive or medical differences between people with translocation trisomy 21 and those with complete trisomy 21.

Sometimes, a parent who does not have Down syndrome may carry a translocation in chromosome 21 that can be passed on to children and cause Down syndrome. Studying the parents’ chromosomes can reveal whether this is the cause of the syndrome. A genetic counselor can assist families affected by translocation trisomy 21 in understanding the risk of Down syndrome in future pregnancies.

Risk Factors

According to the Centers for Disease Control and Prevention (CDC), approximately 6,000 babies are born in the United States each year with Down syndrome.

Down syndrome is the most frequent chromosomal cause of mild to moderate intellectual disability, and it occurs in all ethnic and economic groups.

Researchers know some, but not all, of the risk factors for Down syndrome. For example, parents who have a child with Down syndrome or another chromosomal disorder, or who have a chromosomal disorder themselves, are more likely to have a child with Down syndrome.

In the United States, demographic factors also affect the risk for a child to be born with Down syndrome. These factors include geographic region, maternal education, marital status, and Hispanic ethnicity.

Because the likelihood that an egg will contain an extra copy of chromosome 21 increases significantly as a woman ages, older women are much more likely than younger women to give birth to an infant with Down syndrome. Although women older than 35 years of age make up a small portion of all births in the United States each year, about one-half of babies with Down syndrome are born to women in this age group.

Diagnosis

Healthcare providers can check for Down syndrome during pregnancy or after a child is born. There are two types of tests for Down syndrome during pregnancy:

  • A prenatal screening test. This test can show an increased likelihood that a fetus has Down syndrome, but it cannot determine whether Down syndrome is definitely present. If a screening test shows an increased likelihood, a diagnostic test can be ordered.
  • A prenatal diagnostic test. This test can determine with certainty whether Down syndrome is present. Diagnostic tests carry a slightly greater risk to the fetus than screening tests.

The American Congress of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women be offered a Down syndrome screening test.

Prenatal Screening for Down Syndrome

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

  • A blood test and an ultrasound test during the first trimester of pregnancy. This is the most accepted approach for screening during the first trimester. A blood test enables a health care provider to check for “markers,” such as certain proteins, in the mother’s blood that suggest an increased likelihood of Down syndrome. Then the health care provider does an ultrasound test, which uses high-frequency sound waves to create images. An ultrasound can detect fluid at the back of a fetus’s neck, which sometimes indicates Down syndrome. The ultrasound test is called measurement of nuchal translucency. During the first trimester, this combined method results in more effective or comparable detection rates than methods used during the second trimester.
  • A blood test during the second trimester of pregnancy. As in the first trimester, a blood test enables a healthcare provider to check for markers in the mother’s blood. A triple screen looks for levels of three different markers; a quadruple screen looks for levels of four different markers.
  • A combined test (sometimes called an integrated test). This approach uses both a blood test and an ultrasound during the first trimester, as well as a second-trimester blood test. Healthcare providers then combine all these results to produce one Down syndrome risk rating.

If a woman is pregnant with twins or triplets, a blood test will not be as reliable, because the substances from a Down syndrome fetus may be harder to detect.

Prenatal Diagnostic Testing for Down Syndrome

If a screening test suggests the likelihood of Down syndrome, a diagnostic test can be performed. ACOG recommends that pregnant women of all ages be given the option of skipping the screening test and getting a diagnostic test first. Until recently, only women over age 35 and other at-risk women were offered this option, because diagnostic tests carry a slight risk of miscarriage. Before having diagnostic testing, a pregnant woman and her family may want to meet with a genetic counselor to discuss their family history and the risks and benefits of testing in their specific situation.

Diagnostic testing for Down syndrome involves removing a sample of genetic material. After it is removed, the sample is checked for extra material from chromosome 21, which may indicate that a fetus has Down syndrome. Parents usually get the results of the test a week or two later. The following procedures are used to extract samples.

  • Amniocentesis. A healthcare provider takes a sample of amniotic fluid, which is then tested for the extra chromosome. This test cannot be done until week 14 to 18 of the pregnancy.
  • Chorionic villus sampling (CVS). A healthcare provider takes a sample of cells from a part of the placenta, which is the organ that connects a woman and her fetus, and then tests the sample for the extra chromosome. This test is done between weeks 9 and 11 of pregnancy.
  • Percutaneous umbilical blood sampling (PUBS). A healthcare provider takes a sample of fetal blood in the umbilical cord through the uterus. The blood is then tested for the extra chromosome. PUBS is the most accurate diagnostic method and can confirm the results of CVS or amniocentesis. However, PUBS cannot be performed until later in the pregnancy, between weeks 18 and 22.

Prenatal diagnostic testing does involve some risk to the mother and fetus, including a slight risk of miscarriage. If you and your family are considering prenatal diagnostic testing for Down syndrome, discuss all the risks and benefits with your healthcare provider.

Chromosomal Testing of Maternal Blood

A pregnant woman who is at risk for having an infant with Down syndrome can also have a chromosomal test using her blood. A mother’s blood carries DNA from the fetus, which may show extra chromosome 21 material. A more invasive test would then usually confirm the blood test.

Testing and In Vitro Fertilization

Another approach to diagnosis is used in conjunction with in vitro fertilization. Preimplantation genetic diagnosis (PGD) allows clinicians to detect chromosome imbalances or other genetic conditions in a fertilized egg before it is implanted into the uterus.

This technique is useful mostly for couples who are at risk of passing on a variety of genetic conditions, including X-linked disorders, as well as couples who have suffered repeated spontaneous pregnancy losses, sub-fertile couples, or those at risk for single-gene disorders.

Those interested in PGD should have genetic counseling and should consider close monitoring and additional testing during their pregnancies, given some increased risk of chromosomal abnormalities arising secondary to the in vitro fertilization process.

Diagnosis of Down Syndrome After Birth

A diagnosis of Down syndrome after birth is often based initially on physical signs of the syndrome.

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