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Overview of Genetic Disorders

by Jeffrey S. Dungan, MD

  • Before women become pregnant, they and their partner should speak with their health care practitioner about their risk of having a baby with a genetic disorder.

  • Risk factors include older age in the woman, a family history of genetic abnormalities, a previous baby with a birth defect or miscarriage, and a chromosomal abnormality in one of the prospective parents.

  • Testing for genetic disorders is offered to all women but is particularly important if a couple’s risk is higher than normal.

A big concern of prospective parents is whether their baby will be healthy. Some problems that occur in babies are due to genetic disorders. These disorders result from abnormalities in one or more genes or in chromosomes (see Genes and Chromosomes and see Overview of Chromosomal Disorders). Some abnormalities are hereditary. That is, they are passed down from generation to generation. Others—said to occur spontaneously—result when genetic material in the parents’ sperm or egg cells or in the cells of the developing embryo is damaged by chance or by drugs, chemicals, or other damaging substances (such as x-rays).

Couples who are thinking of having a baby should speak with their health care practitioner about the risks of genetic abnormalities (prenatal genetic counseling). They can discuss precautions that they can take to help prevent some genetic abnormalities. For example, women can avoid exposure to toxic substances and radiation. Couples can also ask their doctor to determine whether their risk of having a baby with a hereditary genetic abnormality is higher than average. If so, tests that can help assess those risks more precisely (genetic screening—see Genetic Screening) can be done. If these tests show a high risk of passing on a serious genetic abnormality, the couple can consider the following:

  • Contraception

  • Artificial insemination if the man has an abnormal gene

  • Use of an egg from another woman if the woman has an abnormal gene

  • In vitro (test tube) fertilization (see Infertility:In vitro (test tube) fertilization (IVF)) with analysis of the embryo's genes before the embryo is transferred to the woman’s uterus (called preimplantation genetic diagnosis)

If the woman is already pregnant, the doctor explains what procedures can be used to test the fetus during the pregnancy (prenatal diagnostic testing—see Prenatal Diagnostic Testing). The doctor also explains what options are available if an abnormality is diagnosed. Abortion is one of these options. In some cases, the abnormality can be treated. Sometimes the couple is referred to a genetic specialist to discuss the issues.

Couples should take time to absorb the information and should ask any questions they have.

Did You Know...

  • The chance of having a baby with Down syndrome at age 36 is about 1 in 300.

  • The chance of having a baby with Down syndrome at age 40 is about 1 in 100.

Risk Factors

All pregnancies involve some risk of genetic abnormalities. However, certain conditions increase risk.

Abnormalities due to several factors

Some birth defects, such as cleft lip or palate, result from abnormalities in one or more genes plus exposure to certain other factors, including substances in the environment (called multifactorial inheritance). That is, the abnormal gene makes the fetus more likely to develop a birth defect, but the birth defect usually does not develop unless the fetus is exposed to specific substances, such as certain drugs or alcohol. Many common birth defects, such as heart malformations, are inherited in this way.

Neural tube defects

Neural tube defects are birth defects of the brain or spinal cord (see Neural Tube Defects). Examples are spina bifida (in which the spine does not completely close, sometimes exposing the spinal cord) and anencephaly (in which a large part of the brain and skull is missing). In the United States, neural tube defects occur in about 1 in 1,000 births. For most of these defects, inheritance is multifactorial (abnormal genes plus other factors). Other factors include

  • Family history: The risk of having a baby with a neural tube defect is increased by having a family member, including the couple’s children, with such a defect (family history). For couples who have had a baby with spina bifida or anencephaly, the risk of having another baby with one of these defects is 2 to 3%. For couples who have had two children with one of these defects, the risk is 5 to 10%. However, about 95% of neural tube defects occur in families without a history of neural tube defects.

  • Folate deficiency: Risk may also be increased by a diet that is low in folate, a vitamin (see Folate). Folate supplements help prevent neural tube defects. Therefore, daily folate supplements are now routinely recommended for all women of childbearing age, particularly for pregnant women. Folate is usually included in prenatal vitamins.

  • Geographic location: Risk also varies based on where a person lives. For example, risk is higher in the United Kingdom than in the United States.

A few neural tube defects result from hereditary abnormalities in a single gene, from chromosomal abnormalities, or from exposure to drugs.

Counseling about prenatal diagnosis by amniocentesis and ultrasonography is recommended for couples who have at least a 1% risk of having a baby with a neural tube defect.

Chromosomal abnormalities

Many chromosomal abnormalities (see also Overview of Chromosomal Disorders), mainly those involving an abnormal number of chromosomes or an abnormality in a chromosome's structure, can be detected by standard chromosomal testing. These abnormalities occur in about 1 of 200 live births and account for at least half of all miscarriages that occur during the 1st trimester. Most fetuses that have chromosomal abnormalities die before birth. Among live-born babies, Down syndrome is the most common chromosomal abnormality.

Several factors increase the risk of having a baby with a chromosomal abnormality:

  • Woman’s age: The risk of having a baby with Down syndrome increases with a woman’s age—steeply after age 35.

  • Family history: Having a family history (including the couple’s children) of a chromosomal abnormality increases the risk. If a couple has had one baby with the most common form of Down syndrome (trisomy 21) and the woman is younger than 30, the risk of having another baby with a chromosomal abnormality is increased to about 1%.

  • Birth defect in a previous baby: Having had a live-born baby with a birth defect or a stillborn baby—even when no one knows whether the baby had a chromosomal abnormality—increases the risk of having a baby with a chromosomal abnormality. About 30% of babies born with a birth defect and 5% of visibly normal stillborn babies have a chromosomal abnormality.

  • Previous miscarriages: Having had several miscarriages may increase the risk of having a baby with a chromosomal abnormality. If the fetus in a first miscarriage has a chromosomal abnormality, a fetus in subsequent miscarriages is also likely to have one, although not necessarily the same one. If a woman has had several miscarriages, the couple’s chromosomes should be analyzed before they try to have another baby. If abnormalities are identified, the couple may choose to have prenatal diagnostic testing early in the next pregnancy.

  • Chromosomal abnormality in a prospective parent: Rarely, a prospective parent has a structural chromosomal abnormality that increases the risk of having a baby with a structural chromosomal abnormality. A chromosomal abnormality in one or both parents increases the risk, even if the affected parent is healthy and has no physical sign of the abnormality. Doctors suspect such an abnormality when couples have had several miscarriages, problems with infertility, or a baby with a birth defect. For such couples, the risk of having a baby with a serious chromosomal abnormality is increased, as is the risk of miscarrying.

Some chromosomal abnormalities cannot be detected by standard chromosomal testing. Most of these abnormalities are too small to be seen with a microscope, so they are sometimes called submicroscopic abnormalities. For example, a very small part of a chromosome may be missing (called a microdeletion), or a chromosome may have a very small extra part (called a microduplication). How often microdeletions and microduplications occur is unknown. However, about 15% of children with structural birth defects or delayed development have them, even though results of standard chromosomal testing are normal. Tests called microarray testing can detect microdeletions and microduplications. Doctors may offer microarray testing before birth in certain circumstances—for example, when birth defects are detected in a fetus.

What Is the Risk of Having a Baby With a Chromosomal Abnormality*?

Age of Woman

Risk of Down Syndrome

Risk of Any Chromosomal Abnormality

20

1 in 1,667

1 in 526

22

1 in 1,429

1 in 500

24

1 in 1,250

1 in 476

26

1 in 1,176

1 in 476

28

1 in 1,053

1 in 435

30

1 in 952

1 in 384

32

1 in 769

1 in 323

34

1 in 500

1 in 238

36

1 in 294

1 in 156

38

1 in 175

1 in 102

40

1 in 106

1 in 66

42

1 in 64

1 in 42

44

1 in 38

1 in 26

46

1 in 23

1 in 16

48

1 in 14

1 in 10

*This table includes only chromosomal abnormalities that can be detected by standard chromosomal testing. Risks of having a baby with submicroscopic chromosomal abnormalities (which can be detected only by special testing) are not included.

Data based on information in Hook EB: Rates of chromosome abnormalities at different maternal ages. Obstetrics and Gynecology 58:282-285, 1981; and Hook EB, Cross PK, Schreinemachers DM: Chromosomal abnormality rates at amniocentesis and in live-born infants. Journal of the American Medical Association 249(15):2034-2038, 1983.

Single-gene disorders

In these disorders, only one pair of genes is involved. A gene may have a mutation, which interferes with its normal function and can lead to disease or birth defects. The risk of such disorders depends on whether the disorder develops when only one gene in the pair has a mutation (such genes are dominant) or when both genes must have mutations (such genes are recessive—see Inheritance Patterns).

Risk also depends on whether the gene is located on the X chromosome (see Inheritance Patterns : X-Linked Inheritance). There are 23 pairs of chromosomes. One pair, the X and Y chromosomes (sex chromosomes), determines sex. All the rest of the chromosomes are called autosomal chromosomes. Women have two X chromosomes, and men have one X chromosome and one Y chromosome. If the abnormal gene is located on the X chromosome, the disorder it causes is called X-linked (sex-linked). If boys inherit an abnormal gene for an X-linked disorder (on the X chromosome), they have the disorder even if the gene is recessive, because they have only one X chromosome, which has abnormal gene. They do not have a normal X chromosome to override the one with the abnormal gene. If a male fetus inherits a dominant X-linked gene, the pregnancy typically ends in miscarriage. If girls inherit one abnormal gene for an X-linked disorder, they have the disorder only if the gene is dominant. If the gene is recessive, they develop the disorder only if they inherit two abnormal genes, one from each parent..

If the prospective mother and father are related, they are more likely to have the same mutation in one or more of the genes that cause autosomal recessive disorders. Thus, the risk of such disorders is increased.

When One Parent Has an Abnormal Gene

Inheritance Pattern

Chance of Inheriting the Disorder

Chance of Being a Carrier*

Autosomal dominant

50% for sons and daughters

0%

Autosomal recessive

25% for sons and daughters

67% for children with no symptoms of the disorder

X-linked dominant

50% when the mother has the gene, usually only in daughters because the abnormal gene is often lethal in sons

0%

X-linked recessive

50% for sons when the mother has the gene

50% for daughters when the mother has the gene

100% for daughters when the father has the gene

*Carriers have only one abnormal gene and usually have no symptoms of the disorder that the gene causes.

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