Birth defects

• Birth defects can cause disabilities and even death.
• Alcohol and drug use while pregnant can cause birth defects.
• Ask your provider what you can do to prevent birth defects.

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About 1 in 150 babies in the United States is born with a chromosomal abnormality (2). These abnormalities are caused by errors in the number or structure of chromosomes. Many children with a chromosomal abnormality have mental and/or physical birth defects. Some chromosomal abnormalities result in miscarriage or stillbirth. Understanding what chromosomes are may make it easier to understand the wide range of problems chromosomal abnormalities can cause.

What are chromosomes?
Chromosomes are tiny, string-like structures in cells of the body that contain the genes. Humans have about 20,000 to 25,000 genes that determine traits like eye and hair color; genes also direct the growth and development of every part of the body (4). Each person normally has 23 pairs of chromosomes, or 46 in all. We inherit one chromosome per pair from our mother and one from our father.

What causes chromosomal abnormalities?
Chromosomal abnormalities usually result from an error that occurs when an egg or sperm cell develops. It is not known why these errors occur. As far as we know, nothing that a parent does or doesn’t do before or during pregnancy can cause a chromosomal abnormality in his or her child.

Egg and sperm cells each contain 23 chromosomes. When they join together, they form a fertilized egg with 46 chromosomes. But sometimes something goes wrong before fertilization. An egg or sperm cell may divide incorrectly, resulting in an egg or sperm cell with too many or too few chromosomes.

When this cell with the wrong number of chromosomes joins with a normal egg or sperm cell, the resulting embryo has a chromosomal abnormality. A common type of chromosomal abnormality is called a trisomy. This means that an individual has three copies of a specific chromosome, instead of two. For example, individuals with Down syndrome generally have three copies of chromosome 21 (though a small number of cases are caused by chromosomal rearrangements).

In most cases, an embryo with the wrong number of chromosomes does not survive. In such cases, the pregnant woman has a miscarriage. This often happens very early in pregnancy, before a woman may realize she’s pregnant. More than 50 percent of first-trimester miscarriages are caused by chromosomal abnormalities in the embryo (1).

Other errors can occur before fertilization. These errors can alter the structure of one or more chromosomes. Individuals with structural chromosomal abnormalities usually have the normal number of chromosomes. However, small pieces of a chromosome (or chromosomes) may be deleted, duplicated, inverted, misplaced or exchanged with part of another chromosome. These structural rearrangements may have no effect on a person if all of the chromosome is there but just rearranged. In other cases, the rearrangements may result in pregnancy loss or birth defects.

Errors in cell division can occur soon after fertilization. This can result in mosaicism, a condition in which an individual has cells with different genetic makeups. For example, individuals with the mosaic form of Turner syndrome are missing an X chromosome in some, but not all, of their cells. Some individuals with chromosomal mosaicism may be mildly affected, but the severity of the condition depends largely on the percentage of abnormal cells.

How are chromosomal abnormalities diagnosed?
Chromosomal abnormalities can be diagnosed before birth using prenatal tests [amniocentesis or chorionic villus sampling (CVS)] or after birth using a blood test. Cells obtained from these tests are grown in the laboratory, and then their chromosomes are examined under a microscope. The lab makes a picture (karyotype) of all the person’s chromosomes, arranged in order from largest to smallest. The karyotype shows the number, size and shape of the chromosomes and helps experts identify any abnormalities.

The American College of Obstetricians and Gynecologists recommends that all pregnant women be offered a screening test for Down syndrome and certain other chromosomal abnormalities, regardless of the woman’s age (2). Screening may consist of a maternal blood test done in the first trimester (at 11 to 13 weeks of pregnancy) along with a special ultrasound of the back of the baby’s neck. It also can be a maternal blood test done in the second trimester (at 15 to 20 weeks). A screening test helps identify pregnancies that are at higher-than-average risk of these abnormalities. However, a screening test cannot diagnose Down syndrome or other chromosomal abnormalities. Providers offer women who have an abnormal screening test result amniocentesis or CVS to diagnose or rule out these disorders.

What are the most common chromosomal abnormalities?
The first 22 pairs of chromosomes are called autosomes. Some common abnormalities of these chromosomes include:

Down syndrome: This is one of the most common chromosomal abnormalities, affecting about 1 in 800 babies (3). Individuals with Down syndrome have varying degrees of intellectual disability, characteristic facial features and, often, heart defects and other problems.

The outlook for children with Down syndrome is far brighter than it once was. Most have intellectual disabilities in the mild to moderate range. With early intervention and special education, many learn to read and write and participate in diverse childhood activities.

The risk of Down syndrome and other trisomies increases with the mother’s age. The risk of having a baby with Down syndrome is about (1):

• 1 in 1,300 at age 25
• 1 in 1,000 at age 30
• 1 in 400 at age 35
• 1 in 100 at age 40
• 1 in 35 at age 45

Trisomies 13 and 18: These trisomies usually are more severe than Down syndrome, but fortunately less common. About 1 in 16,000 babies is born with trisomy 13 (also called Patau syndrome), and about 1 in 5,000 with trisomy 18 (also called Edwards syndrome) (4). Babies with trisomies 13 or 18 generally have severe intellectual disabilities and many physical birth defects. Most affected babies die before their first birthday.

The last pair of chromosomes are the sex chromosomes, called X and Y. Generally, females have two X chromosomes, and males have one X chromosome and one Y chromosome. Sex chromosome abnormalities may cause infertility, growth abnormalities, and, in some cases, behavioral and learning problems. However, most affected individuals live fairly normal lives. Common sex chromosome abnormalities include:

Turner syndrome: This abnormality affects about 1 in 2,500 girls (4). Girls with Turner syndrome have one X chromosome and are missing all or part of the other X chromosome. They usually are infertile and do not undergo normal puberty changes unless they are treated with sex hormones. Affected girls are short, though treatment with growth hormone can help increase height. Some have other health problems, including heart and kidney defects. Girls with Turner syndrome generally have normal intelligence, though some have learning difficulties, particularly with mathematics and spatial concepts (5).

Triple X: About 1 in 1,000 females has an extra X chromosome (4). Affected girls tend to be tall. They usually have no physical birth defects, experience normal puberty and are fertile. Affected girls usually have normal intelligence, though many have learning problems. Because these girls are healthy and have a normal appearance, their parents often don’t know they have a chromosomal abnormality. Some parents may learn that their daughter has this abnormality if they have prenatal testing (with amniocentesis or CVS).

Klinefelter syndrome: This abnormality affects about 1 in 500 to 1,000 boys (4). Boys with Klinefelter syndrome have two, or occasionally more, X chromosomes along with their Y chromosome. Affected boys usually have normal intelligence, though many have learning problems. As adults, they produce lower-than-normal amounts of the male hormone testosterone (and often are treated with this hormone) and are infertile.

XYY: About 1 in 1,000 males is born with one or more extra Y chromosomes (4). Affected males are sometimes taller than average, have normal sexual development and are fertile. Most have normal intelligence, though some have learning, behavioral and speech/language problems. As with triple X females, many affected males and their families don’t know they have a chromosomal abnormality unless it is diagnosed with prenatal testing.

Are there other, less common, chromosomal abnormalities?
New techniques for analyzing chromosomes have made it possible to identify tiny chromosomal abnormalities that may not be visible even under a high-powered microscope. As a result, more parents are learning that their child has a chromosomal abnormality. Some of these uncommon chromosomal abnormalities include:

• Deletions: A small section of a chromosome is missing.
• Microdeletions: An extremely small amount of a chromosome is missing, possibly only a single gene.
• Translocations: A section of a chromosome is attached to another chromosome.
• Inversions: A section of chromosome is snipped out and reinserted upside down.
• Duplications: A section of a chromosome is duplicated, so there is extra genetic material.
• Ring chromosome: Material is deleted at both ends of a chromosome, and the new ends join together to form a ring.

Some chromosomal abnormalities are so rare that only one or a few children are known to be affected. In such cases, it may be impossible for a health care provider to predict a child’s long-term health and development. Some abnormalities (such as some translocations and inversions) may not affect a person’s health if no genetic material is missing or duplicated.

Some uncommon disorders can be caused by small chromosomal deletions. Examples are:

• Cri-du-chat (cat cry) syndrome (deletion on chromosome 5): Affected children have a cat-like, high-pitched cry during infancy, intellectual disabilities and physical abnormalities. About 1 in 20,000 to 50,000 babies is born with this disorder (4).
• Prader-Willi syndrome (deletion on chromosome 15): Affected children usually have intellectual disabilities or learning disabilities, behavioral problems and short stature. They also may develop extreme obesity. About 1 in 10,000 to 25,000 babies is affected (4).
• 22q11 deletion syndrome (deletion on chromosome 22): About 1 in 4,000 babies is born with deletions in a specific region of chromosome 22 (4). These deletions cause a variety of problems that can include heart defects, cleft lip/palate, immune system abnormalities, characteristic facial features and learning disabilities. Certain combinations of these features are sometimes called DiGeorge or velocardiofacial syndrome. Individuals with this disorder have a 50-percent chance of passing the chromosomal abnormality on to their offspring with each pregnancy (4).
• Wolf-Hirschhorn syndrome (deletion on chromosome 4): This disorder is characterized by intellectual disabilities, heart defects, poor muscle tone, seizures and other problems. It affects about 1 in 50,000 babies (4).

With the exception of individuals with 22q11 deletion syndrome, individuals with these disorders generally do not reproduce.

Are all children with the same chromosomal abnormality alike?
No. Each child with a chromosomal abnormality should be evaluated as an individual. Even people with apparently identical chromosomal abnormalities can differ substantially from each other. How a person is affected depends greatly, but not wholly, on the exact genetic material involved. Each chromosome contains hundreds to thousands of genes, and each gene influences different characteristics or body functions.

New techniques of analyzing chromosomes sometimes can pinpoint exactly where missing or extra genetic material comes from. If providers know what genes are contained in that section and their function, they sometimes can give parents a better prediction of a child’s future development.

Will brothers and sisters of a child with a chromosomal abnormality have the same problem?
Parents who have had a baby with a chromosomal abnormality should consult a genetic counselor. These health professionals help families understand what is known about the causes of a birth defect and the chances that the birth defect will recur in another pregnancy. Fortunately, in most cases, parents of a baby with a chromosomal abnormality learn that the risk is low.

However, there are exceptions. For example, a small number of parents of children with Down syndrome or various other chromosomal abnormalities have a chromosomal rearrangement called a balanced translocation. It does not affect their own health, but the rearrangement can be harmful when passed on to their offspring. Sometimes a genetic counselor recommends blood tests to determine whether parents carry such a rearrangement in order to give parents the most accurate picture of their risk in another pregnancy. Testing may occasionally show that a parent of a child with 22q11 deletion syndrome has a mild, previously undiagnosed form of the disorder that can be passed along to future offspring.

Where can families affected by chromosomal abnormalities turn for help?
An affected baby’s health care provider should be able to discuss specific medical problems in detail or refer a family to appropriate specialists. Parents also may find it helpful to contact a support group of families of children affected by the same or similar chromosomal abnormalities. A genetic counselor is a good source of referrals to appropriate support groups. Some of them include:

• Chromosome Deletion Outreach
  (561) 395-4252
• Chromosome 22 Central
  (705) 268-3099
• 5 P Minus Society (cat cry syndrome) 
  (888) 970-0777
• Genetic Alliance
  (202) 966-5557
• Klinefelter Syndrome and Associates 
  (also has material on Triple X syndrome and XYY)
  (888) 999-9428
• National Down Syndrome Society
  (800) 221-4602
• National Organization for Rare Disorders 
  (800) 999-6673
• Prader-Willi Syndrome Association 
  (800) 926-4797
• Support Organization for Trisomy 18, 13, and Related Disorders
  (800) 716-7638
• Turner Syndrome Society
  (800) 365-9944

References

1. American College of Obstetricians and Gynecologists. (2007). Invasive prenatal testing for aneuploidy. (Practice Bulletin No. 88). Washington, D.C.: Author.
2. American College of Obstetricians and Gynecologists. (2007). Screening for fetal chromosomal abnormalities. (Practice Bulletin No. 77). Washington, D.C.: Author.
3. Centers for Disease Control and Prevention. (2009). Down syndrome. Retrieved March 11, 2009 from: www.cdc.gov/ncbddd/birthdefects/DownSyndrome.htm.
4. National Institutes of Health. (2009). Genetics home reference. Retrieved May 2, 2009 from: http://ghr.nlm.nih.gov.
5. Turner Syndrome Society. (2009). Turner syndrome: The basics. Retrieved May 29, 2009 from: www.turnersyndrome.org.

December 2009