Genetic disorders are caused by abnormalities in one or more genes or chromosomes. Some genetic disorders are hereditary and others are spontaneous.
Hereditary genetic disorders are passed down from generation to generation.
Spontaneous genetic disorders are not passed down from one generation to another, but they occur when genetic material in the father’s sperm or mother's egg cells or in the cells of the developing embryo is damaged by chance or by medications, chemicals, or other damaging substances (such as radiation).
Before pregnancy, prospective parents should speak with their health care professional about their risk of having a baby with a genetic disorder.
Risk factors include older age in the woman or man, a family history of genetic abnormalities, a chromosomal abnormality in one of the prospective parents, a previous miscarriage or stillbirth, or a previous baby with a birth defect.
Testing for genetic disorders is offered to all women but is particularly important if a couple’s risk is higher than average.
(See also Overview of Chromosome and Gene Disorders and Overview of Birth Defects.)
Prospective parents who are thinking of having a baby should speak with a health care professional about the risks of genetic abnormalities (prenatal genetic counseling). Prospective parents can review their family history and other medical history with their doctor or a genetic counselor to determine whether their risk of having a baby with a hereditary genetic abnormality is higher than average. If so, tests to assess those risks more precisely (genetic carrier screening) can be done. If genetic screening tests show a prospective parent has a genetic abnormality, the couple and doctor can discuss the options for avoiding having the abnormality pass down to a child.
spina bifida (a neural tube defect) and avoid exposure to toxic medications, substances, and radiation.
Types of and Risk Factors for Genetic Disorders
All cells in the human body contain deoxyribonucleic acid (DNA). Genes are segments of DNA that contain the code for a specific protein that functions in one or more types of cells in the body or the code for another type of molecule called ribonucleic acid (RNA). Chromosomes are structures within cells that contain a person's genes.
Genetic disorders can be caused by an abnormality in a single gene, multiple genes, or part or all of a chromosome. The following percentage of all babies have an abnormality:
0.5% have a chromosomal disorder.
1% have a single-gene disorder.
1% have a disorder caused by defects in several genes.
All pregnancies involve some risk of genetic abnormalities. Certain conditions in the parents increase risk, such as advanced age.
Chromosomal abnormalities
Chromosomal abnormalities, many of which involve an abnormal number of chromosomes or an abnormality in a chromosome's structure, occur in about 1 of 200 live births in the United States. Chromosomal abnormalities may be fatal to the fetus and are commonly found in a fetus when a pregnancy ends in miscarriage or stillbirth. Down syndrome (trisomy 21) is the most common chromosomal abnormality in babies born alive.
Several factors increase the risk of having a baby with a chromosomal abnormality:
Mother’s age: The risk of having a baby with Down syndrome increases with a mother’s age—steeply after age 35. The chance of having a baby with Down syndrome is about 1 in 590 before age 35 and 1 in 100 at or after age 35.
Father's age: If a man is older than 50 years, there may be an increased risk of some types of fetal genetic abnormalities.
Family history: Having a family history of a chromosomal abnormality increases the risk. If a couple has had one baby with the most common form of Down syndrome, the risk increases for future pregnancies.
Birth defect in a previous baby: Having had a baby with a birth defect or a stillborn baby—even when it is not known whether the baby had a chromosomal abnormality—increases the risk of having a baby with a chromosomal abnormality. About 15% of babies born with a birth defect and about 8 to 16% of visibly normal stillborn babies have a chromosomal abnormality.
Previous miscarriages: Chromosomal abnormalities are estimated to be the cause of 50 to 80% of all miscarriages in the first trimester. These miscarriages are usually due to spontaneous genetic abnormalities. If a woman has had 2 or more miscarriages, the prospective parents' chromosomes should be analyzed for numeric or structural abnormalities before trying to have another baby.
Chromosomal abnormality in a prospective parent: Rarely, a prospective parent has a structural chromosomal abnormality, which increases the risk of having a baby with a similar 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.
Did You Know...
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Some chromosomal abnormalities can only be detected with specialized testing. Most of these abnormalities are too small to be seen with a microscope, so they are sometimes called submicroscopic abnormalities (or copy-number variants). 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). Approximately 6% of children with birth defects have these types of submicroscopic abnormalities. Tests called chromosomal microarray testing can detect microdeletions and microduplications. Doctors may offer microarray testing before birth in certain circumstances—for example, when birth defects are suspected in a fetus.
Single-gene disorders
In single-gene 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 also Inheritance of Single-Gene Disorders.)
Risk also depends on whether the gene is located on the X chromosome. 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 an X-linked (sex-linked) disorder.
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 an 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.
However, girls must inherit two abnormal genes to develop an X-linked disorder if the gene is recessive. If the abnormal gene is dominant, only one abnormal gene is required for the disorder to develop.
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.
Neural tube defects
Neural tube defects are birth defects of the brain or spinal cord. (The brain and spinal cord develop from a part of the embryo called the neural tube). Examples are spina bifida (in which the spine does not completely close, sometimes exposing the spinal cord) and anencephaly (in which part of the brain and skull is missing). For most of these defects, the cause is a combination of abnormal genes and other factors. Other factors include
Family history: The risk of having a baby with a neural tube defect is increased by having a family history of such a defect. If either prospective parent has had a previous baby with spina bifida or anencephaly, the risk of having another baby with one of these defects is higher. This risk increases even more if a parent has had two children with one of these defects.
A few neural tube defects result from hereditary abnormalities in a single gene, from chromosomal abnormalities, or from exposure to certain medications or chemicals.
Counseling about prenatal diagnosis by amniocentesis and ultrasonography is recommended for women who have at least a 1% risk of having a baby with a neural tube defect.
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. 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 illicit drugs or alcohol. Many common birth defects, such as heart malformations, are inherited in this way.
Family History Assessment
Any prospective parent can request genetic screening, but screening is particularly recommended when
One or both partners know they have a genetic abnormality.
Family members have a genetic abnormality.
Parents have racial or ethnic ancestry with an increased risk of certain disorders.
Because parent ethnicity or race is often complex and not well defined and because prenatal genetic testing is becoming much less expensive and quicker, some health care professionals are starting to screen all potential (and expectant) parents, regardless of ethnicity.
Some genetic disorders are not hereditary and thus cannot be identified by screening the parents.
To determine whether a couple has an increased risk of having a baby with a genetic disorder, doctors ask the couple about the following:
Disorders that family members have had
The cause of death in family members
The health of all living first-degree relatives (parents, siblings, and children) and second-degree relatives (aunts, uncles, and grandparents)
Miscarriages, stillborn babies, or babies who have died soon after birth in the couple or in family members
Babies with birth defects born to the couple or to family members
Parents who are second cousins or more closely related to each other (which increases the risk of having the same abnormal gene)
Ethnic or racial background (certain groups are at higher risk of certain disorders)
Information about three generations is usually needed. If the family history is complicated, information about more distant relatives may be needed. Sometimes doctors review the medical records of relatives who may have had a genetic disorder.
Genetic Carrier Screening
Carriers are people who have an abnormal gene for a disorder but who do not have any symptoms or visible evidence of the disorder.
In carriers, the abnormal gene is usually recessive—that is, two copies of the gene are needed to develop the disorder (see Recessive Disorders). Such carriers have one normal gene and one abnormal gene for the disorder.
Traditionally, screening tests are offered to parents at risk of being asymptomatic carriers for certain disorders, such as sickle cell anemia, the thalassemias, Tay-Sachs disease, and cystic fibrosis. Some health care professionals are starting to screen all potential (and expectant) parents, regardless of risk (called universal carrier screening).
Carrier screening usually consists of analyzing the DNA from a blood sample. But sometimes a sample of cells from the inside of the cheek is analyzed. People provide the sample by swishing a special fluid in their mouth, then spitting it into a specimen container, or by rubbing a cotton swab inside their cheek.
Ideally, carrier screening is done before a woman becomes pregnant. If it is done afterward and if it indicates that both partners have a recessive gene for the same disorder, they may decide to have prenatal diagnostic testing. That is, the fetus may be tested for the disorder before birth.
Abnormal Results of Genetic Carrier Testing
If genetic screening tests show a high risk of passing on a serious genetic abnormality, the couple can consider the following:
Using sperm from another man if the man has an abnormal gene
Using an egg from another woman if the woman has an abnormal gene
Having prenatal diagnostic testing to do genetic testing of an embryo or fetus during a pregnancy
Choosing not to become pregnant
During the process of becoming pregnant or during a pregnancy, there are several options to test an embryo or fetus directly for genetic abnormalities (see Prenatal Testing for Genetic Disorders and Birth Defects). Options include:
Preimplantation genetic diagnosis: A few cells are removed from an embryo and tested before the embryo is transferred to a woman’s uterus, this can only be done if a woman becomes pregnant using in vitro (test tube) fertilization
Chorionic villus sampling: A sample of chorionic villi (part of the placenta) is removed and tested, this test is usually done between 10 and 13 weeks of pregnancy
Amniocentesis: A sample of the fluid that surrounds the fetus (amniotic fluid) is removed and analyzed, this test is usually done at 15 weeks of pregnancy or later
If an abnormality is diagnosed, the doctor explains what is likely to happen to a fetus with that particular genetic abnormality or birth defect. Sometimes the parents are referred to a genetic specialist to discuss the issues. In some cases, the abnormality can be treated. In other cases, it is likely the fetus will die before birth or will have a limited life expectancy after birth. For some abnormalities, the child may have an intellectual disability, physical disability, or other medical problems.
Doctors will explain options, and prospective parents can then decide to continue the pregnancy or have a pregnancy termination. Doctors may advise a woman to get prenatal care at a hospital that provides more extensive services for newborns and children with medical issues.
Parents should take time to absorb the information and should ask any questions they have.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
American College of Obstetricians and Gynecologists: Genetic Disorders: This website provides definitions of genes and chromosomes and basic information about inheritance, risk of having a baby with a birth defect, and testing for genetic and chromosomal abnormalities.
