What Is It?

Genetic testing is used to confirm the presence of genetic diseases, as well as to measure your risk of developing a disease or of passing along a genetic disorder to a child.Today, there are hundreds of genetic tests, some of them for relatively common disorders, such as cystic fibrosis, and others for very rare diseases. A genetic test is fundamentally different from other kinds of diagnostic tests you might take. Indeed, a whole new field, genetic counseling, has grown up around the need to help incorporate family history and genetic testing into modern health care.

The purposes of genetic tests vary. Some genetic tests are used to confirm a preliminary diagnosis based on symptoms. But others measure your risk of developing a disease, even if you are healthy now (presymptomatic testing), or determine whether you and your partner are at risk of having a child with a genetic disorder (carrier screening).

As the name suggests, a genetic test looks at your genes, which consist of DNA (deoxyribonucleic acid). DNA is a chemical message to produce a protein, which has a specific function in the body. Proteins are essential to life—they serve as building blocks for cells and tissues; they produce energy and act as messengers to make your body function. In addition to studying genes, genetic testing in a broader sense includes biochemical tests for the presence or absence of key proteins that signal aberrant gene function.

What do Genetic Tests Test For?

Chromosome Abnormalities
Long strings of DNA condense together, packaging the DNA in the form of a chromosome. Most people have 23 pairs of chromosomes in the nucleus of each cell. One of each chromosome pair is inherited from the mother and the other is inherited from the father. Some tests look at chromosomes for abnormalities such as extra, missing or transposed chromosomal material. The chromosomes hold 20,000 to 25,000 genes, meaning that each chromosome is densely packed with genes. Extra or missing pieces of chromosomes can have a significant impact on the health of an individual. Also, sometimes pieces of chromosomes become switched, or transposed, so that a gene ends up in a location where it is permanently and inappropriately turned on or off. The genes on the chromosomes are responsible for making proteins, which direct our biological development and the activity of about 100 trillion cells in our bodies.

If something goes wrong with an essential protein, the consequences can be severe. For example, a protein called alpha-1 antitrypsin (AAT) clears the lungs of a caustic agent called neutrophil elastase. If the body has an alteration in the gene that makes the protein AAT, the AAT protein may not be made correctly or at all. Then neutrophil elastase will build up in the lungs, and the individual can develop emphysema and other complications.

Most genetic conditions are the result of mutations in the DNA, which alter the instructions for making a given protein. Some mutations are inherited on genes passed down from parents, while others occur during an individual's lifetime. These mutations can lead to diseases ranging from those we think of as "genetic diseases," such as cystic fibrosis or AAT deficiency, to those we think of as degenerative diseases, such as heart disease. In the case of diseases like heart disease, asthma or diabetes, a combination of factors—some genetic, some related to environmental or lifestyle—may work together to trigger the disease.

It's possible to have a mutation, even one for a severe disease, such as cystic fibrosis (CF) and never know it. Almost all humans have two copies of each chromosome and therefore have two copies of each gene, one inherited from the mother and the other from the father. If only one copy of a given gene has a mutation, you are a healthy carrier of the disorder. You "carry" the mutation but do not have the disease. If both copies of a gene have a mutation, you will have the disease. Such disorders are called autosomal recessive. If you are a carrier, the unaltered gene in the pair retains the function. Those who are diagnosed with a recessive disease have inherited two copies of a gene, both carrying a mutation. Therefore, since one of those copies came from the mother and the other from the father, both parents must have at least one copy of the gene with a mutation. If two carriers of the same disease-causing gene have children, each pregnancy has a 25 percent chance of having the disease (because of a 25 percent chance of inheriting both the mother's and the father's mutated copies of the gene), a 50 percent chance of being a carrier and a 25 percent chance of not inheriting the mutation at all.

Some disorders, such as Huntington disease, are autosomal dominant. If a person has one mutated gene, its effects will cause the disease, even if the matching gene is normal. Thus, each child of a parent with Huntington disease has a 50 percent chance of inheriting the gene causing the disease. Osteogenesis imperfecta, which causes brittle bones, is another example of a dominant disorder.

Chromosomes can be one of two types: sex chromosomes or autosomes. Sex chromosomes are X and Y. Most men have an X and a Y, and most women have two Xs. If each parent contributes an X chromosome, the child is a girl; if the father passes on his Y chromosome, the child is a boy. Because girls have two X chromosomes, and therefore two copies of every X-linked gene, they are less likely than boys to have symptoms from X-linked genetic diseases because boys don't have a backup copy if an X-chromosome gene has a mutation. Examples of X-linked diseases include forms of hemophilia and fragile X syndrome (the most common inherited cause of mental impairment). Autosomes are the remaining 22 pairs of chromosomes. Therefore, most diseases are autosomal, or due to genes on the autosomes.

What Genetic Tests Can Find

Unclear Results
Although genetic testing can be very useful in diagnosis, prevention and medical decision-making, genetic tests do not always provide clear answers. One such result is a "variant of uncertain significance." All people have differences in their DNA, so if a new DNA alteration is detected, it may be uncertain as to whether it is associated with disease or is part of normal human variation. Another limitation is that not all genetic tests are created as equals. Since genetic testing can be very expensive, some tests only look for the most common disease-causing mutations. Instead of examining the entire gene, these tests only look for specific, common mutations. If you or your family has a mutation in a portion of the gene that wasn't tested, you will have a negative result, even though you do have a disease-associated mutation. Since genetic tests are not perfect, it is always important that genetic test results be interpreted in combination with medical and family history by a genetic counselor or other genetics-credentialed professional.

The Cost of Genetic Testing

The cost of a genetic test varies dramatically, ranging from $100 to more than $3,200. The difference stems largely from the variation in labor intensity of different tests. Some tests look for a limited number of mutations (sometimes only one) known to cause a disease. This type of test may only look at one piece of DNA code, for one specific mutation. Other genetic tests require sequencing of the entire gene, where they examine each piece of DNA code comprising the gene, which can be thousands of pieces of code.

The explosion of genetic research now taking place is expected to bring prices down and dramatically increase the number of tests available. Tests are becoming available to predict your genetic risk of more common disease, such as heart disease and diabetes. This information will help you and your health care professional develop specific strategies for prevention. Preventive efforts can include changing your lifestyle or perhaps taking certain medications, which may be tailored to your specific genetic profile, and early screening to head off the worst complications should you develop the disease.

Facts to Know

  1. A genetic test examines some aspect of a person's genetic makeup, either directly through gene sequencing or indirectly through the measure of marker chemicals. Such a test usually aims to determine whether a person has, is at above-average risk of having or is a carrier of a disease-causing genetic mutation.
  2. Because the nature of genetic testing is so complex, with implications for both the person being tested and his or her family, genetic counseling is desirable before taking any genetic test and essential for proper interpretation of test results.
  3. Genetic counselors are committed to protecting your privacy. They will not contact other family members without your permission, though they may encourage you to share results that might affect your relatives.
  4. A maternal serum screening test indicates whether a fetus is at above-average risk of being born with certain genetic disorders, most notably Down syndrome, trisomy 18 and open neural tube defects. The test is not diagnostic and a positive result is usually followed up with a diagnostic amniocentesis or chorionic villus sampling test. Out of 1,000 serum screening tests, 50 will suggest increased risk for open neural tube defects, but only one or two of the fetuses will have such a defect. Likewise 40 of 1,000 will test positive for increased risk of Down syndrome, but only one or two will fetuses will actually have the disease.
  5. Some genetic disorders are recessive and X-linked, which means they are caused by a mutation in a gene that resides on the X chromosome. Females have two X chromosomes, but males have only one. If a mother has a disease-linked recessive gene mutation in one of her X chromosomes, she is a carrier of the disorder but will have no or minimal symptoms herself. If she has a son, he will have a 50 percent risk of inheriting the disorder; a daughter will have a 50 percent chance of being a carrier.
  6. In addition to disorders that have surfaced in your family, you may want to consider carrier testing for genetic conditions that occur with greater frequency in your particular ethnic group. For example, Caucasians have a higher risk of cystic fibrosis, while those of African descent are at high risk of carrying a mutation that can cause sickle cell disease. A battery of tests exists for those of Ashkenazi (Eastern European) Jewish descent. Remember that the best time for carrier testing is before a pregnancy.
  7. Children should not be screened for carrier status or for diseases that won't trouble them until much later in life because the information is not relevant to their health care. Most geneticists and genetic counselors consider such testing unethical, since children are not in the position to make their own decisions as to whether or not they want the test (known as informed consent).
  8. Within a family, two or more incidences of the same type of cancer or related cancers, or one at under age 50 may indicate a hereditary pattern. A genetic counselor can take a closer look at your family history to determine whether an inherited mutation appears to be responsible for the cancers in your family and can advise you as to whether testing is available.
  9. The best-known cancer predisposition tests look for mutations in the BRCA1 and BRCA2 genes. Women with a BRCA mutation face a lifetime breast cancer risk of up to 88 percent, compared to about 13 percent in the general population, and lifetime ovarian cancer risk of up to 60 percent, compared to a population risk of about 1.4 percent.
  10. If your family has a history of colorectal and related cancers, you may want to consider genetic counseling and risk assessment. Several colorectal cancer syndromes can be responsible for hereditary cancer risk. One such syndrome is Lynch Syndrome. The syndrome increases lifetime risk of colorectal cancer to 80 percent vs. a 5.4 percent population risk, but also boosts risk of endometrial cancer (to 60 percent), ovarian cancer (to 12 percent) and gastric cancer (to 13 percent). Those with Lynch Syndrome also face a higher risk of cancers of the kidney and ureter, brain and small bowel.

Questions to Ask

Review the following Questions to Ask about genetic testing so you're prepared to discuss this important health issue with your health care professional.


  1. Could my symptoms be caused by a genetic disorder? Is testing available?
  2. Are you experienced in diagnosing and treating genetic disorders? If not can you make a referral?
  3. How accurate is this test?
  4. What are the risks of the test?
  5. What information will come out of the test?
  6. What will a positive or negative result tell me?
  7. Is an uncertain result possible, and what would that mean?
  8. What are my options for preventing or treating the disease if a mutation is found?
  9. What other family members might be affected?
  10. How do I broach the subject with them?
  11. Could this disorder affect my children before they're grown? Should they be tested?
  12. What measures are in place to protect my privacy?
  13. How often have you performed the test?
  14. How experienced is the lab in performing this test?
  15. How long will it take to get results back?
  16. How could this test affect my health care?

Cancer Predisposition Testing

  1. Does my family history suggest a pattern of inherited cancer?
  2. Is there a test available to determine which family members are most at risk?
  3. What are my chances of developing cancer if I test positive for a mutation?
  4. How does my risk change with age?
  5. What are my options if I test positive?
  6. How frequently should I have screenings?
  7. Are preventive measures such as surgery or pharmaceuticals available?

Carrier Screening And Preconception Counseling

  1. Based on family history and ethnicity, which carrier tests should my partner and I consider?
  2. What criteria are you using to determine which tests are right for us?
  3. Would other centers recommend a different lineup of tests?
  4. What are the options if a result suggests the possibility of having a child with a genetic disorder?

Prenatal Testing

  1. How early or late in my pregnancy can this test be performed?
  2. What are the risks of the test?
  3. Is this a risk screening test or a diagnostic test?
  4. What are the options if the test finds a problem?

Key Q&A

  1. What is genetic testing?
    A genetic test looks at a particular aspect of your genetic makeup, either directly through gene sequencing or indirectly through measure of marker chemicals. Testing may be done for a variety of purposes:
    • Diagnosis, to determine if a person has a genetic disorder (often performed in conjunction with analysis of symptoms)
    • Risk screening, to determine if a person is at increased risk of having a genetic disorder (with follow-up diagnostics usually called for if a test is positive)
    • Predisposition testing, to determine if a person is at higher risk of developing a particular disease later in life
    • Carrier testing, to determine if a person is a carrier of a disease-causing mutation and may be at risk of having a child with the disease
  2. What does it mean if I'm a carrier for a disease?
    Genes come in pairs, and a carrier of a recessive disease has one mutated, disease-causing gene and a corresponding normal gene. The normal gene compensates for the mutated copy and the person never develops the disease. If two carriers of the same disease-causing gene have a child, however, that child has a 25 percent chance of having the disease (because of a 25 percent chance of inheriting two mutated copies of the gene), a 50 percent chance of being a carrier and a 25 percent chance of not inheriting the mutation at all.
  3. If my partner and I have carrier testing, will the results tell us whether or not our children will be affected?
    In most cases, the test will provide only guidance as to your child's risk for being born with a particular disorder or being a carrier of the disease. Because you contribute only one of the two copies you have of each gene, each child has a 50 percent chance of inheriting any particular mutation from you. Each child likewise has a 50 percent chance of inheriting any particular mutation your partner has. Thus, if you are both carriers of the same autosomal recessive disorder, each child has a 25 percent risk of being born with the disease, a 50 percent risk of being a carrier and a 25 percent chance of not inheriting a mutation at all. A genetic counselor can help you sort through the possible combinations in your situation and describe options for pregnancy planning and prenatal testing.
  4. Why do I need a genetic counselor in addition to my doctor?
    Most counselors and geneticists have extensive training and certification specifically related to genetics and genetic testing. Additionally, most physicians do not have time to spend an hour or more providing education, information collection, risk assessment and informed consent. Hence, many physicians make referrals when the issue arises. Genetic counselors usually work with geneticists (MDs or PhDs), particularly for more complex cases.
  5. If I have a test, will I face job or insurance discrimination if the result is positive?
    The Genetic Information Nondiscrimination Act of 2008 (GINA), a new federal law that protects Americans from being treated unfairly because of genetic diseases and mutations that may affect their health, was recently passed. This law specifically addresses protections in regard to health insurance and the workplace.
  6. Why are some genetic tests so much more expensive than others?
    Some tests look for mutations by actually sequencing the entire gene; these tests, which may cost more than $3,000, look for mutations by determining the exact order of the chemicals that comprise the gene and compare the order to that of a normal gene. Other, less expensive tests look for individual, commonly known disease-causing mutations. It's like going to a grocery store. If you have never been to that store before and you are looking for a bottle of ketchup, you may go through every aisle. This is the equivalent of sequencing; looking through the entire gene for the mutation. If you have been there before and know where the ketchup is, you can go directly to the location in the store, which is like specific point mutation testing—you know exactly where the mutation is located.
  7. A relative has canceram I at risk, too?
    Your family history provides the best clues. Two or more relatives with early onset (before age 50 or 60, depending on the cancer) of related cancers or diagnosis of two or more related cancers in the same person suggest the possibility of a genetic link that could put you at risk. Related cancers are not always as obvious as you might think. For example, colon cancer and endometrial cancer can be caused by the same genetic mutation. Talk to a genetic counselor to get a better idea of your risk and find out whether predisposition testing is available.
  8. Isn't my health my own business? Why should my extended family be involved?
    By their very nature, genetic diseases are a family affair, with mutations passed on to multiple generations. When a disease is clearly hereditary, testing positive for a disease-causing mutation or being diagnosed with the disease provides knowledge that other family members may be at risk. A genetic counselor can help you identify who may be at risk and should be notified and can help you handle the situation if there is estrangement between relatives.
  9. What's the difference between amniocentesis and chorionic villus sampling? How do I decide which is right for me?
    Both procedures provide for diagnosis of specific chromosomal and genetic disorders in the fetus. Amniocentesis is more likely to be offered as a follow-up to an abnormal maternal serum screening test because results of the screen are obtained too late in pregnancy for CVS. However, CVS, which is done at 10 to 12 weeks gestation, or amniocentesis, are offered in the following situations:
    • You will be 35 or older at delivery.
    • A genetic disorder has surfaced on either side of the family.
    • You or your partner has had a previous child with a birth defect.
    • You and your partner are carriers of the same recessive disorder.
    Both chorionic villus sampling (CVS) and amniocentesis can cause cramping, and a small number of women have miscarriages following the procedures (the risk is higher with CVS). It takes one to two weeks to get results from either test. Amniocentesis is performed more frequently and should be the choice if you're at risk having a child with neural tube defects. The procedure is performed at 15 to 18 weeks of pregnancy. CVS can be performed earlier, at 10 to 12 weeks, and is popular with parents who would like to know results before the pregnancy starts to show. The procedure is not available everywhere, however.
  10. If I get a negative result from a cancer predisposition test, can I still develop that particular kind cancer?
    Yes. Your lifetime risk for breast cancer, even in the absence of a gene mutation, is about 12 percent. At least 90 percent of breast cancer is not due to a single, inherited cancer predisposition gene. A negative BRCA test result simply means you don't face a higher-than-average risk for the disease due to a hereditary cancer syndrome.

Genetic Counseling

What Is Genetic Counseling?

Because the nature of genetic testing is so complex, with implications for both the person being tested and his or her family, genetic counseling is an important part of pre- and post-genetic testing. Unlike most medical appointments, a counseling session may be a family affair, with participation of all concerned relatives.

A genetic counselor is a health care professional who is an expert in counseling, human genetics and genetic testing. He or she reviews your family and medical histories to determine if there appears to be a hereditary pattern of disease. A genetic counseling session can last any amount of time, depending upon the situation. Genetic counseling typically includes:

  • gathering background medical information about you and your family
  • risk assessment for having a genetic disease or mutation
  • discussion about genes that may be appropriate for testing, if indicated
  • discussion about the risks, benefits and limitations of testing
  • providing information on inheritance, the genetic testing procedure, the possible results and what they mean
  • informed consent, if genetic testing is indicated and you elect to have it

Genetic counseling will educate you so you can make an informed decision. Genetic counselors are trained to assist you in the decision-making process, and genetic testing is never required.

Because family history is so crucial in assessing for a genetic condition and determining which genes to consider testing, a counselor may request medical records to confirm a diagnosis, especially if you're trying to determine whether a family pattern of cancer is hereditary.

Family member recollections can be inaccurate—who had which disease or even what type of disease. Many conditions either were not discussed or not diagnosed in past decades. A genetic counselor can listen to a family account and help tease out details to better identify potential patterns.

Privacy Concerns

Genetic counselors are committed to protecting the privacy of their patients. They will not contact other family members without your permission, though they may encourage you to share results that might affect the health of your relatives. The Genetic Information Nondiscrimination Act of 2008 (GINA) is a new federal law that specifically addresses genetic discrimination in regard to health insurance and employment. The law took effect in 2009.

How to Find a Counselor

You can find a genetic counselor at https://www.nsgc.org, the Web site for the National Society of Genetic Counselors. The core credentials are a master's degree in the field and certification conferring the designation of certified genetic counselor (CGC).

Carrier Screening

Characteristics of Carriers
Anyone can carry a genetic mutation for an autosomal recessive disease such as cystic fibrosis, sickle cell disease or Tay-Sachs disease and not even know it. That's because carriers of these mutations have no symptoms—in fact, they don't have the disease.

Genes come in matched pairs, except for those on the sex chromosomes. In the case of autosomal recessive disorders, if only one copy of the gene is damaged, the unaffected gene can still function, usually preventing symptoms of the disease. In fact, a disease-causing mutation can be inherited through dozens of generations of a family without anyone showing symptoms of the disease.

If two carriers of the same mutated gene have a child, the chance of both parents passing on his and her mutated copy is 25 percent, in which case the child would have the disease. There is also a 25 percent chance that both parents would pass on their unaffected genes, in which case the child would not have the disease and would not be a carrier. Finally, there is a 50 percent chance that the child will be like the parents and will be a healthy carrier (with one unaffected gene and one with a mutation, but not developing the disease).

The exception to this pattern occurs if a disorder is recessive and X-linked. The X is the symbol for the larger sex chromosome. A child who inherits two X chromosomes is a girl. A child with an X chromosome and a Y chromosome is a boy. If a mother has a disease-linked recessive mutation on one of her X chromosomes, she is a carrier of the disorder but should have no or minimal symptoms herself since she has an unaffected X, usually preventing the development of the disease. If the mother who carries an affected X has a son, he will have a 50 percent risk of inheriting the disorder because he will inherit either the mother's affected X or unaffected X. If a male inherits the mother's X which carries a mutation, and since a male has no second X chromosome (instead he has Y chromosome, hence being a male), he will then develop the disease. A daughter will have a 50 percent chance of being a carrier, like her mother, since she has inherited her second, functional X from her father.

Fragile X syndrome, as its name suggests, is one such X-linked disorder. The severity of Fragile X can greatly vary. Boys who inherit the mutation usually develop the disease, the most common form of genetically inherited mental retardation. Girls who inherit a fragile X mutation are more likely to be carriers, although some females do develop symptoms. If you have a family history of mental retardation, testing can determine whether a Fragile X mutation is responsible and whether you are a carrier.

As with other types of testing, genetic counseling can help you understand carrier screening. A counselor can also help you develop strategies for sharing the information with other family members who may also be at risk of carrying the mutation.

Why Have Carrier Screening?
Carrier screening is recommended for any disorder or mutation that has been identified in a family member. In addition, you should consider carrier screening for mutations found frequently in your particular ethnic group. The prevalence of genetic disorders is linked closely to ethnic heritage. Caucasians, for example, have a much higher risk than most other groups for cystic fibrosis, and those of African American descent are more likely to be carriers of sickle cell anemia mutations.

Most carrier screening tests don't sequence an entire gene. Instead they focus on specific mutations known to be common in particular groups. The results are generally accurate (90 to 95 percent). Since most genetic screening tests only look for the common mutations, there is a residual risk that there is a less common mutation that wasn't tested.

The following are some examples of ethnicities and the conditions that are found more frequently in those groups.

  • Caucasians: phenylketonuria, hemochromatosis, cystic fibrosis and alpha 1-antitrypsin deficiency.
  • African Americans: sickle cell disease and thalassemia
  • East Asians (except Koreans): thalassemia
  • Irish, French Canadians and Cajuns: Tay-Sachs disease
  • Mediterraneans: thalassemia and familial Mediterranean fever
  • Southeast Asians (Cambodians, Laotians and Vietnamese): hemoglobinopathies (disorders of hemoglobin, the oxygen-carrying component of red blood cells)

There are also "genetic screening panels." A panel is typically used for individuals of a specific ethnicity that have a risk for several associated genetic conditions or common mutations for which genetic tests can be performed at one time. One example of a screening panel is the Ashkenazi Jewish Screening Panel. The Ashkenazi Jews are of Central and East European descent, and they account for about 80 percent of the Jewish population in the United States.

The Ashkenazi Jewish screening panel varies depending on the program and laboratory. Some test only for Tay-Sachs and Canavan diseases; other panels may include disorders such as Gaucher disease, Bloom syndrome, Fanconi anemia, Niemann-Pick disease, hereditary deafness and familial dysautonomia.

Many panels also include a screen for cystic fibrosis (CF). This condition is not more common in the Ashkenazi population. Caucasians are actually more likely to carry CF mutations than other groups. Still, the ratio of the Ashkenazi population that carries known CF mutations is fairly high, about one in 25. Three specific mutations are common in this population, making testing more specific.

Experts Recommend Preconception Screening

You might think that if you and your partner come from different backgrounds, carrier screening is unnecessary. The American College of Obstetricians and Gynecologists, however, advises that if one partner in a couple is at high risk and the other is not, the high-risk partner should be screened. If that person tests positive as a carrier, the other partner should be screened.

Genetics experts recommend carrier screening before a couple plans to conceive. Be proactive in seeking preconception genetic counseling. It ensures you the most options, and your genetic counselor can guide you through which screening tests are most appropriate.

If two prospective parents are found to be carriers of a disease, their options include:

  • adoption
  • use of donor sperm or a donor egg
  • in vitro fertilization and preimplantation genetic diagnosis of the embryos
  • prenatal testing (If a fetus is identified to carry mutations that could cause disease or disability, some individuals decide to end the pregnancy, while others use the information to prepare for a child having the genetic condition.)

For some recessive diseases, even though an individual has two mutated genes, the clinical severity can vary from patient to patient. Someone with particular disease mutations, for example, may not have symptoms until middle age or may go a lifetime asymptomatic, making decisions about testing—and what to do if a fetus turns out to be affected—difficult for prospective parents. It is very important to discuss the details of your genetic test results with a clinician who specializes in interpreting results.

Cancer Screening

Testing for Inherited Cancer
If you have a family history of cancer, particularly cancers that occur before age 50, you may want to explore cancer genetic counseling. Approximately 5 percent to 10 percent of cancers are due to a specific inherited gene mutation that increases cancer risk. Hereditary cancers are not always obvious. A mutation that leads to breast cancer in your grandmother may lead to ovarian cancer in your aunt. Likewise, a mutation that causes colon cancer in your sister may cause endometrial cancer in your daughter.

To determine whether your family's cancers might be hereditary, a genetic counselor will need to know medical details about the family, especially those who have been diagnosed with cancer. Two important things to know about your relatives who have had cancer are: age at diagnosis and the exact organ where the cancer originated. Be prepared for a counselor to request medical records. One of several conclusions may be made about your family history:

  • The cancers in the family, even if there are several, may be "sporadic" and it is highly unlikely that they are due to inherited genetic mutation.
  • The pattern fits a known hereditary cancer syndrome for which genetic testing is available. Those who test positive for the mutation would need to be vigilant about prevention and screening measures. If a mutation has been identified in the family and an individual is negative, that person can be managed similar to others who do not have a mutation. If a mutation has not been identified in a family, yet the family history is still consistent with a hereditary cancer syndrome, your providers will tailor your screening and management plan accordingly.
  • Family history is somewhat suggestive of an inherited pattern, but is not consistent with a known hereditary cancer risk syndrome. In this situation, the screening and prevention methods are tailored to the family history of cancer.

Some inherited cancer syndromes for which testing is available are:

  • Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 or BRCA2 genes and is often referred to as the "breast cancer genes." BRCA1 and BRCA2 mutations are mostly associated with breast and ovarian cancer. Some families also exhibit other cancers such as male breast cancer, pancreatic cancer, melanoma, gastric cancer, prostate cancer and others.
  • Lynch syndrome can be caused by mutations in the MLH1, MSH2 and MSH6 genes. Such mutations are also linked to cancers of the endometrium, stomach, small bowel, ureter, ovary and collecting system of the kidneys. This syndrome is sometimes known as hereditary non-polyposis colorectal cancer, although this term is misleading because people with Lynch syndrome do develop polyps.
  • Familial adenomatous polyposis (FAP), or attenuated familial adenomatous polyposis (AFAP), is caused by a mutation in the APC gene. Typical FAP results in the growth of hundreds or thousands of polyps in the colon beginning at young ages, sometimes in the teens. AFAP is also due to a mutation in the APC gene, but individuals have fewer polyps.
  • Ataxia telangiectasia is a complex autosomal recessive disorder caused by an ATM (ataxia telangiectasia mutated) gene. Among other effects, including dysfunction of the cerebellum (the part of the brain that controls motor function and balance), A-T has been linked to lymphomas and leukemia. It is diagnosed in childhood. As individuals live longer, other cancers have been observed, including ovarian and breast cancers, stomach cancer and melanoma.
  • Multiple endocrine neoplasia (MEN) 1 and 2 are two separate rare disorders caused by mutations in the MEN1 or RET genes, respectively; MEN1 or 2 can lead to cancer in one of the endocrine glands, such as the parathyroid, thyroid, pancreas, pituitary or adrenal gland.

Your body has certain genes that regulate when your cells divide and how often they divide. You were born with two copies of each cell control gene, one inherited from your mother and one from your father. Most mutations occur accidentally as part of natural aging. If a mutation occurs on one copy of a given cell-control gene, the second copy remains functional. But if the second copy of a cell-control gene develops a mutation, that cell loses its ability to control cell division, potentially resulting in a tumor and possibly cancer. Cancers are typically due to accidental or sporadic mutations that occur throughout a lifetime.

Some people inherit a copy of a cell control gene that already has a mutation. These individuals still carry a functioning copy of the cell control gene, which can still regulate the cell growth. Over time, the unaffected gene may develop a sporadic mutation, resulting in both copies functioning improperly, allowing that cell to become cancerous and multiply. Inheriting a mutation associated with cancer does not cause the cancer.

Not everyone with a hereditary cancer predisposition mutation will develop cancer. For those who carry a cancer predisposition mutation, the risks vary greatly and depend upon the specific gene and syndrome. Those with a BRCA mutation face a lifetime breast cancer risk of up to 88 percent, compared to about 13 percent in the general population, and a lifetime ovarian cancer risk of up to 60 percent, compared to a population risk of about 1.4 percent.

The knowledge that you are positive for a mutation allows you to take action to reduce your risk through preventive measures, such as more frequent screening to detect early growths or tumors, taking protective medications or even prophylactic surgery to remove the organ prone to cancer.

Other Predisposition Syndromes

These are only a few examples of cancer predisposition syndromes. You may want to consider genetic counseling if one of the following are true:

  • Three or more blood-related individuals in your family have the same or related cancers.
  • You have early onset of a cancer
  • You have more than one diagnosis of cancer.

As with other cancer syndromes, it is always best if someone who is affected with cancer be initially tested.

Breast Cancer Screening

Are You A Candidate For Breast Cancer Testing?
Because breast cancer is one of the most common cancers, many individuals are becoming aware of genetic testing for BRCA mutations. BRCA testing is not appropriate for most people.

If you think there's a possibility that your family has a hereditary cancer pattern, talk to a genetic counselor. The genetic counselor will assess the likelihood for you to carry a cancer predisposition mutation and, if indicated, discuss the option of genetic testing.

You might want to seek genetic counseling and breast and ovarian cancer risk assessment if you have one of the following:

  • Breast cancer at an early age
  • Two primary breast cancers or breast cancer and an incidence of ovarian, fallopian tube or primary peritoneal cancer
  • Two or more primary breast cancers or breast cancer and ovarian, fallopian tube or primary peritoneal cancers in one or more close relatives from the same side of the family (maternal or paternal)
  • A combination of breast cancer with one or more of the following: thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumors, diffuse gastric cancer, dermatological manifestations or leukemia/lymphoma on the same side of the family
  • Member of the family with a known mutation in a cancer susceptibility gene
  • Any male breast cancer
  • Any ovarian, fallopian tube or primary peritoneal cancer

Your ethnic background may come into play with breast cancer risk as well, if you are of Ashkenazi Jewish descent. Women with such a background are about 10 times more likely to have a mutation than women in the general population. If you are of Ashkenazi Jewish descent, you may also consider genetic counseling if there is any family history of breast or ovarian cancer. An Ashkenazi Jewish BRCA testing panel is available. This test looks for three specific mutations that account for 90 percent of the positive BRCA1/2 gene changes in this population. If the test is negative, BRCA sequence analysis may be ordered.

As you think about your family history, keep in mind that these mutations can be inherited maternally or paternally. Be sure to look at your father's family history, in addition to your mother's.

It is important to remember that even when a family has a mutation, not everyone will inherit it. For example, if your father carries a BRCA1 mutation , he still has an unaffected copy of BRCA1. It depends on which gene is inherited by each child, and there is a 50 percent chance that each child will inherit the BRCA mutation. Thus, in a group of siblings, some may inherit a mutation, while others may not.

BRCA testing has several limitations. Not all families that have cancers consistent with a BRCA mutation will test positive. This is because it is believed that there are other genes involved with breast and ovarian cancer risk. It is suspected that approximately 16 percent of HBOC families have mutations in genes other than BRCA1 and BRCA2 . For this reason, it is ideal to test the person in the family who is most likely to test positive, to confirm whether a mutation can be identified. Another limitation of this test is that sometimes people receive an "uncertain" result. No matter whether the result is positive, negative or uncertain, your genetic counselor will thoroughly explain the results and what it means for you and your cancer risk.

There are several other cancer syndromes that have breast cancer as a feature. For this reason, the family history information is crucial. It can greatly change what gene may be suspected. Pathology reports, medical records and even death certificates can be useful for your genetic counselor.

Several variations of BRCA testing are available. Your genetic counselor can help determine which is most appropriate.

Comprehensive sequence analysis of BRCA1 and BRCA2 costs about $3,120. If a mutation is identified in the first person tested, subsequent tests for other family members are approximately $440 each. The reason the first test is so expensive is that the genes must be fully sequenced to identify the mutation. Once a mutation is found, the technicians know where exactly to look in the other relatives' DNA samples. Those of Ashkenazi Jewish descent (Eastern European background) may be tested using the BRCA Ashkenazi panel, examining three specific mutations most commonly found in this population, which costs approximately $535. A new addition to BRCA testing became available in 2006. This test looks for large deletions and duplications of the BRCA genes. This test is called BART and costs $650.

Again, it is important to regularly contact your genetic counselor to update your family history. New genetic testing becomes available over time. Also, learning of additional family members and their cancers may change your genetic assessment and lead to considering testing for a different gene.

If no one in your family has been diagnosed with breast or ovarian cancer, then your risk of carrying a BRCA1/2 mutation is quite low and testing would not be recommended. Keep in mind, however, that absence of these mutations doesn't mean you won't develop cancer. At least 90 percent of breast and ovarian cancer cases are "sporadic," meaning they don't stem from inherited mutations, but rather are caused by a mutation or a combination of mutations that arise over time. Therefore, regardless of your genetic status, be sure to follow the recommendations of your health care professional, such as having an annual breast examination by your health care professional (called a clinical breast examination) and a mammogram, if appropriate (schedule based on age).

Finally, if you test negative, you should still be assessed for cancer risk, based on your family history and medical history. This information can help determine whether you are at average risk, using general screening guidelines, or whether your screening regimen should be tailored to you.

Did You Test Positive?
If you test positive for a BRCA mutation, there are options for minimizing your cancer risk, but none of them reduce your risk to zero. No individuals are the same, and you should ask your health care professional to help you weigh the risks and benefits for each of the following options.

  • Breast self-exam training and education, starting monthly breast self-exams at age 18.
  • Clinical breast exam, semiannually, starting at age 25.
  • Annual mammogram and breast MRI starting at age 25.
  • Risk-reducing mastectomy.
  • Risk-reducing salpingo-oophorectomy (removal of ovaries and fallopian tubes), ideally between 35 and 40 years old, or upon completion of child bearing, or individualized based on earliest age of onset of ovarian cancer in the family.
  • For those who have not elected salpingo-oophorectomy, concurrent transvaginal ultrasound and CA-125 (a blood test that may indicate certain cancers) every six months starting at age 35, or 5 to 10 years earlier than the earliest age of diagnosis of ovarian cancer in the family.
  • Chemoprevention options, such as tamoxifen and raloxifene. These medications are typically used after breast cancer to reduce the risk for another breast cancer, but in high-risk individuals, they can be offered to reduce the risk for an initial breast cancer.
  • Investigational imaging and screening studies, when available.

Oophorectomy is increasingly being recommended for women who test positive for BRCA mutations and are either finished with childbearing or are certain that they do not want children. Removal of the ovaries not only reduces ovarian cancer risk 80 percent or more in both pre- and post-menopausal women, it also reduces breast cancer risk 50 percent in premenopausal women. That's because the ovaries produce estrogen, which stimulates breast growth and is linked to cancer risk. Removing the ovaries also removes your body's source of estrogen. Therefore, estrogen levels diminish rapidly and trigger menopausal symptoms, such as hot flashes, vaginal dryness and bone loss, among other short-term physical and emotional changes and long-term health risks associated with menopause. For some women, "surgical menopause," through removal of the ovaries, can trigger more sudden and severe menopausal symptoms than when menopause occurs spontaneously at the end of a woman's childbearing years—a transition that typically takes about five years in a woman's late 40s.

Postmenopausal hormone therapy (often referred to as hormone replacement therapy or HRT) can be prescribed prior to or just after surgery to mitigate menopausal symptoms. However, women, health care professionals and the federal government are scrutinizing the use of postmenopausal hormone therapy more closely than ever before and its safety for both long-term and short-term use is in question.

The U.S. Food and Drug Administration (FDA) now requires a highlighted and boxed warning on all estrogen projects for use by postmenopausal women. The so-called "black box" is the strongest step the FDA can take to warn consumers of potential risks from a medication. The warning highlights the increased risk for heart disease, heart attacks, stroke and breast cancer from supplemental estrogen—risks illuminated by part of the Women's Health Initiative study, which was abruptly halted when the risks were identified.

The "black-box" warning also advises health care professionals to prescribe estrogen products at the lowest dose and for the shortest possible length of time. Women taking estrogen projects are cautioned to have yearly breast exams and receive periodic mammograms.

Because every woman's risk profile is different, women who are thinking about taking postmenopausal hormone therapy or are currently taking it, need to review their options and treatment plans with their health care professional in light of the FDA's warning.

Since then, new lower-dose versions of the hormone therapies used to treat symptoms of menopause have been developed. The FDA approved a low-dose version of the combination estrogen-progestin treatment Prempro and the estrogen-only Premarin.

Colon Cancer Screening

Are You A Candidate For Colon Cancer Testing?
If your family has a history of colorectal and related cancers, you may want to seek genetic counseling and consider genetic testing for mutations associated with colon cancer risk. There are several colorectal cancer predisposition syndromes, all with great overlap. It is important to be evaluated by a specialist in cancer genetics, who can identify which gene(s) are most appropriate to test, given the subtle differences in the syndromes.

One colorectal cancer predisposition syndrome is Lynch Syndrome (otherwise known as hereditary nonpolyposis colon cancer). The syndrome increases lifetime risk of colorectal cancer to 80 percent vs. a 5.4 percent population risk and also elevates your risk of endometrial cancer, ovarian cancer and gastric cancer. Those with Lynch Syndrome also face a higher risk of cancers of the kidney and ureter, liver, brain, pancreas, stomach and small bowel. Sometimes before genetic testing is performed, a preliminary test on the actual cancer tumor can help suggest whether genetic testing is indicated, and if so, which gene to test.

Other examples of colorectal cancer predisposition syndromes are FAP, AFAP and MYH-associated polyposis. Several other syndromes are also associated with colorectal cancer risk.

To determine whether testing might be appropriate for your family, a genetic counselor would look for the number of cancers in your family, ages of onset, the specific types of cancer and the family's history of colon polyps. Pathology reports are quite useful, because the type of colon cancer, the types of polyps and the locations of cancer and polyps can help direct which genes should be tested.

Many aspects of the testing parallel BRCA testing. For Lynch Syndrome, the ideal initial candidate for testing is a person who has been diagnosed with cancer. This test can cost approximately $3,640.

Screening options for those who have a colorectal cancer predisposition syndrome vary, depending on which gene may have a mutation. Some options may include the frequent colonoscopies, starting at an age depending on the syndrome or 10 years younger than the youngest age of colorectal cancer diagnosis in the family, whichever is earlier. Sometimes prophylactic surgery to remove the colon may be an option.

Genetic Testing & Children

Genetic testing is not appropriate for minors (under the age of 18), unless the test is used to diagnose a symptomatic child, or if knowing the genetic status of a presymptomatic child will impact his or her medical management.

Newborn screening programs are now widely available for genetic diseases treatable early in life. Such a test can indicate elevated risk of a disorder, which should be followed up with further diagnostics. Below are the most commonly administered newborn screening tests, though remember that the number and types of newborn screening tests performed vary from state to state (check with your health care professional to find out which tests are performed in the state where you plan to deliver):

  • Phenylketonuria (PKU) is characterized by an inability to metabolize an amino acid called phenylalanine and causes mental retardation unless a specialized phenylalanine-free, low-protein diet is put in place. Aspartame should be avoided if you have PKU.
  • Hypothyroidism can interfere with growth and mental development if not treated.
  • Galactosemia can cause mental retardation if not treated with a diet free of a sugar called galactose, which is found in dairy products.
  • Sickle cell disease is an inherited disorder in which red blood cells are abnormally shaped.

Currently, all 50 states provide newborn screening for PKU and congenital hypothyroidism.

Prenatal Genetic Testing

There are two types of prenatal tests: screening tests and diagnostic tests. Prenatal screening is meant to identify women at an increased risk for the pregnancy to be affected by a disease. Diagnostic prenatal testing is used to confirm whether or not a pregnancy is affected by a given condition.

Almost all pregnant women in the United States have a maternal serum screening test performed. This is performed with a blood sample and is usually done between week 15 and week 18 of the pregnancy (as measured from the start of the most recent menstrual period). The test estimates your risk of having a baby with:

  • An open neural tube defect. When the neural tube fails to close, the baby is born with an opening in the head (anencephaly) or spinal cord (spina bifida). Babies with anencephaly are stillborn or die soon after birth; those with spina bifida need surgery and may be paralyzed. The severity of spina bifida can vary greatly. One way to reduce your risk of having a child with a neural tube defect is to take folic acid (400 micrograms per day) before conception.
  • Down syndrome (also called Trisomy 21). An extra copy of chromosome 21 causes Down syndrome, characterized by mental retardation, certain facial features and sometimes heart defects.
  • Trisomy 18. An extra copy of chromosome 18 causes this syndrome, which usually proves fatal during the first year of the baby's life and is associated with severe mental retardation.

The blood screen does not look directly at genetic material but instead measures four substances—alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin and Inhibin A—to determine whether you are at increased risk of having a baby with one of these disorders. A key fact to remember is that this test does not diagnose the disorders—it only screens for the substances and shows if there is an increased risk of a disorder. Further testing is always suggested to make a diagnosis.

Indeed, most of the time, the fetus is not affected with the disorder, even if the screening result is abnormal. Out of 1,000 serum screening tests, an average of 50 will suggest an increased risk for open neural tube defects, but only one or two of the fetuses will have such a defect. Likewise an average of 40 out of 1,000 will test positive for increased risk of Down syndrome, but only one or two fetuses will actually have the condition.

Most labs offer the standard "quadruple marker" serum screening test, which detects approximately 75 percent of fetuses affected with Down syndrome among women younger than age 35, and 90 percent of affected fetuses in women 35 and older.

A newer type of prenatal screening test that can be done in the first trimester is becoming much more common. This test assesses the risk for the fetus to have Down syndrome or trisomy 18. The first trimester screening has two parts and both should both be performed between weeks nine and 13 of gestation. One part tests levels of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in the mother's blood. The other measures the nuchal thickening (measure of fetal neck thickness) through a specialized ultrasound. This test detects 85 percent of fetuses with Down syndrome and approximately 90 percent with Trisomy 18. However, it is a screening test and still requires a confirmatory chorionic villous sampling or amniocentesis to make the definite diagnosis. The primary benefit of this screening test is that it can be performed earlier in the pregnancy.

A screening test does not diagnose a condition. It should not be used to make decisions for treatment or pregnancy termination, but rather should be used to determine whether the mother wishes to have diagnostic prenatal testing performed.

Diagnostic Follow-Up In Prenatal Testing
If a screening test indicates a higher-than-average risk, your health care professional may want to perform a basic ultrasound, which can help determine the gestational age of the fetus and show if a woman is carrying twins. If either of these factors accounts for the abnormal screen test result, no further testing is needed. Otherwise, a more detailed ultrasound examination may be performed, which allows a look at the baby's brain and spinal cord, as well as other parts of the body. This ultrasound can often identify an open neural tube defect or other malformation associated with an abnormal screening test.

Your health care provider may suggest you consider either amniocentesis or chorionic villus sampling (CVS). Both are diagnostic tests to determine whether the fetus actually has the disorder in question. Amniocentesis is performed more frequently and should be the choice if you're at risk for having a child with neural tube defects (CVS doesn't detect neural tube defects).

If you have amniocentesis, a doctor will use a needle to withdraw a sample of amniotic fluid (the fluid surrounding the fetus) for analysis. The procedure is typically performed during the second trimester, at 15 to 18 weeks.

Amniocentesis or CVS is offered for high-risk pregnancies, which could include any of the following:

  • you will be 35 years of age or older at delivery
  • your family has a known genetic disorder
  • you have had a previous child with a birth defect
  • you and your partner are carriers of the same recessive disorder
  • other indications as directed by your obstetrician

Both CVS and amniocentesis can cause cramping, and a small number of women have miscarriages following the procedures (the risk is slightly higher with CVS).

CVS is performed at 10 to 12 weeks of gestation and involves analyzing a sample of placental tissue. A thin tube inserted through the vagina and cervix, or the abdomen, and is used to suction out a small tissue sample from the placenta. However, unlike amniocentesis, CVS cannot be used to test for neural tube defects, such as spina bifida and anencephaly. Therefore, it's usually recommended that a woman undergoing CVS also have the prenatal blood test called the maternal serum alpha fetoprotein (MSAFP) screening test, at about 16 to18 weeks of pregnancy.

CVS is more attractive to some women because it can be done much earlier, at 10 weeks to 12 weeks. Many women say that this is a time when pregnancy is still a private issue. But other women feel the slightly higher risk of CVS is unacceptable, and they wait for the amniocentesis. Amniocentesis and CVS can be used to prenatally diagnose many, but not all, genetic disorders. Every prenatal screening and diagnostic test has its benefits, risks and limitations. It is very important to discuss these testing options with your doctor and, if possible, a genetic counselor.

Of course, the ideal time for many tests is before you get pregnant. If you are planning a pregnancy, preconception genetic counseling can be quite helpful, since it offers an opportunity to make decisions without the pressure of an advancing pregnancy. Potential risks for the planned fetus can be identified and testing strategies can be pursued.

Handling The Results
No test guarantees a healthy baby. While amniocentesis and CVS are extremely accurate, they are specific in the types of conditions they can detect. These tests are useful in detecting chromosomal disorders. If a specific single-gene disease is suspected, these tests can also be quite useful but are not perfect. Of course, every genetic test is different, and your genetic counselor should accurately describe what your test will and will not detect. These tests cannot take into account other factors, including sporadic genetic mutations (without a hereditary component), which may affect a child's development.

When an untreatable genetic disorder is diagnosed prenatally, parents have the option of continuing or terminating the pregnancy. A genetic counselor can help you learn more about the disorder and weigh your options in a neutral setting. The decision is a tough one, and parents may weigh such factors as whether the disorder can be treated, the family's ability to manage the disorder or disability, the extent to which an affected child will be disabled or in pain and how long the child is likely to live.

Prenatal testing can be valuable if you opt to continue a pregnancy knowing your child will be born with a particular disease. The diagnosis often can help you, your family and your health care team better manage the pregnancy, the delivery and any treatment the newborn will need.

In rare cases, a disorder diagnosed prenatally can be treated before birth. For example, congenital adrenal hyperplasia, an autosomal recessive condition that causes genital abnormalities in girls, can be treated with hormones given to the mother. But such opportunities to correct birth defects are still the exception.

Types of Diseases

Alpha-1 antitrypsin (AAT) deficiency
Leads to lung damage and emphysema by the third or fourth decade of life. Liver disease may occur in the first few months of life. The condition is worsened by smoking. A replacement therapy is available but in chronically short supply, and it is not known how effective this is once disease has developed or which people would benefit most. You should consider carrier screening if you have a family history of the disease.

Celiac disease
The most common genetic disease in Europe affecting one in 300 people of European descent. In celiac disease, a protein called gluten (found in grains) provokes the body's immune system to destroy the small intestine's nutrient-absorbing villi. This destruction leads to malnourishment, but with a gluten-free diet, the villi heal. A gluten-free diet means avoiding all foods that contain wheat, rye, barley and possibly oats—in other words, most grain, pasta, bread, cereal and many processed foods. Despite these restrictions, people with celiac disease can eat a well-balanced diet with a variety of foods, including bread and pasta. For example, instead of wheat flour, people can use potato, rice, soy or bean flour. Or, they can buy gluten-free bread, pasta and other products. The disease is believed to be underdiagnosed in the United States. Children of a person with celiac disease have about a five percent chance of developing the disease. You may want to consider screening for yourself or a child if a close relative has celiac disease or symptoms such as anemia, delayed growth or weight loss appear. There is an increased incidence of celiac disease in individuals with Down syndrome.

Congenital adrenal hyperplasia (CAH)
Caused by insufficient production of an essential chemical called cortisol. Children with CAH may have male features, such as excess facial hair, and tend to stop growing early and have trouble fighting infections and retaining salt. Girls with the severe form of the condition may have genital defects. The mild form has similar, but less pronounced, symptoms and may go undiagnosed. You may want to consider screening if you have a family history of the disease. During pregnancy, treating the mother can prevent the severe manifestations of CAH.

Cystic fibrosis
Characterized by the production of thick mucus, leading to pulmonary and digestive problems. The disease is caused by a mutated CFTR gene (cystic fibrosis transmembrane regulator). About one in 25 Caucasian Americans is a carrier of a mutation in this gene. Cystic fibrosis occurs most frequently in Caucasians of northern European origin. Because there are many possible disease-causing mutations in the gene, most tests are only about 80 to 85 percent accurate and this may be lower in some ethnic groups. Tests for Ashkenazi Jewish carriers are about 97 percent accurate, however, because there are three specific mutations in this population for this condition.

Fragile X syndrome
An X-linked recessive disorder that is the leading cause of genetically inherited mental retardation. Because the mutation (in a gene called FMR-1) is X-linked, boys are affected more frequently and more severely. Often women are carriers with no symptoms or less severe symptoms; however, females can be affected. The mutation consists of segments of unstable DNA that are repeated; the repeats may lengthen with each succeeding generation, leading to greater impairment in offspring. Consider carrier screening if you have a family history of Fragile X or mental retardation in male relatives.

Hemophilia A and B
X-linked recessive disorders characterized by low levels or absence of one of two essential blood-clotting proteins. About 18,000 people suffer from hemophilia, with hemophilia A accounting for 90 percent of cases. With a few very rare exceptions, hemophilia occurs in males. Treatment with the clotting proteins is expensive. Consider carrier testing if you have a family history of hemophilia or excessive bleeding.

Genetic disorders of the nervous system that primarily affect the development and growth of neural (nerve) cell tissues. These disorders cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities. The neurofibromatoses occur in both sexes and in all races and ethnic groups. Scientists have classified the disorders as neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Brown birthmarks known as "café-au-lait" marks are frequently the first sign noted in NF-1. This is a very variable condition, and you could be so mildly affected you don't even know you have it.

Phenylketonuria (PKU)
Characterized by an inability to metabolize an amino acid called phenylalanine. Buildup of the chemical causes mental retardation, but state-mandated screening programs are able to identify newborns with PKU so that a special phenylalanine-free diet can be started to prevent retardation and other problems. If you were diagnosed with PKU as a child, a special diet should be consumed both before and during pregnancy. You should consider carrier screening if you have a family history of the disease.

Sickle cell disease
A blood disorder caused by a mutation in the gene that expresses the hemoglobin protein. The disease is characterized by anemia and periods of pain. Hemoglobin, the substances that carries oxygen in red blood cells, forms uncharacteristic, rodlike clusters in the cells, giving them a sickle shape and impeding their passage in small blood vessels. The cells create a bottleneck that deprives tissues of oxygen and causes pain. The cells die more quickly than normal red blood cells, leaving the body chronically short of such cells and anemic. About one in 12 African Americans is a carrier.

A term that covers a range of related anemias that vary greatly in severity. A baby with thalassemia major may appear normal during the first year but subsequently develops symptoms such as jaundice (yellowed skin) and low appetite. If untreated, enlargement of the liver and spleen can occur, sometimes leading to heart failure or heightened susceptibility to life-threatening infections.

Von Hippel-Lindau disease (VHL)
A rare, genetic multisystem disorder characterized by the abnormal growth of tumors in certain parts of the body (angiomatosis). The tumors of the central nervous system (CNS) are benign and are comprised of a nest of blood vessels and are called hemangioblastomas (or angiomas in the eye). Hemangioblastomas may develop in the brain, the retina of the eyes and other areas of the nervous system. Other types of tumors develop in the adrenal glands, the kidneys or the pancreas. Gene testing is available.

Recessive Genetic Conditions More Prevalent in Individuals of Ashkenazi Jewish Descent

Canavan disease
A neurodegenerative disease characterized by lack of the aspartoacylase enzyme, which is critical for central nervous system development and function. The progression is similar to Tay-Sachs disease, and affected children usually die by age five. Your doctor, even an ob/gyn, may not be aware of the risk for Canavan disease. The carrier rate is about one in 40 among Ashkenazi Jews.

Congenital deafness
Caused by one of two changes in a gene called Connexin 26. About one in 21 individuals of Ashkenazi Jewish descent has one of the two mutations.

Cystic fibrosis (see general list)

Gaucher disease
Type I is a disorder caused by a lack of glucocerebrosidase, an enzyme that helps clear glucocerebroside from cellular structures called lysosomes. The condition can lead to slower growth in children, bone degeneration, anemia, enlargement of the spleen and liver and thrombocytopenia. A replacement enzyme treatment is available, but the product is expensive—in excess of $100,000 per patient annually. The carrier rate among the Ashkenazi is between one in 10 and one in 15. Not everyone who inherits two Gaucher disease mutations develops the disease or is aware of it.

Tay-Sachs disease
Characterized by absence of hexosaminidase A, an enzyme that breaks down GM2-ganglioside. Without this enzyme, fat builds up in the central nervous system, leading to neurological degeneration. Afflicted children become symptomatic at around six months, and the disease is usually fatal in children within a few years. (Adult-onset forms of Tay-Sachs disease are rarer and less severe.) Carrier screening can be done on a blood sample looking at DNA mutations or enzyme levels, since carriers have reduced levels. A combination of enzyme level and mutation studies is the most accurate test. The carrier rate among the Ashkenazi Jewish population is about one in 27; the rate is about one in 250 among French Canadians, Cajuns and Irish.

Other conditions with a higher carrier rate in the Ashkenazi Jewish population for which testing is available include:

  • Bloom syndrome, a chromosome breakage disorder. Symptoms include growth retardation, skin discoloration and typical facial features. The disease often leads to cancer and sometimes mental retardation. The carrier rate among Ashkenazis is about one in 100.
  • Familial Dysautonomia, a disease that causes the autonomic and sensory nervous system to malfunction. Symptoms include the absence of tears, taste buds and deep-tendon reflexes. The gene was recently identified and carrier screening is available to the general population. That carrier rate is one in 30.
  • Fanconi anemia, a DNA repair disorder that leads to a range of symptoms including thumb and arm abnormalities, skeletal abnormalities, kidney problems, skin discoloration, small head or eyes, mental retardation or learning disabilities, gastrointestinal difficulties, small reproductive organs in males and defects in tissues separating heart chambers. At least five genes are implicated in Fanconi anemia—and it only takes one of them going awry to cause the disease. Type C accounts for most cases of FA in the Ashkenazi Jewish population. Commercial testing is available for this mutation. The carrier rate among the Ashkenazi Jewish population is about one in 89.
  • Niemann-Pick disease, a metabolic disorder caused by insufficient quantities of sphingomyelinase. The result is accumulation of the fatty substance sphingomyelin in the spleen, liver, lungs, bone marrow and, in some patients, the brain. Patients with Type A—predominantly individuals of Ashkenazi Jewish descent—rarely live beyond 18 months. Commercial carrier testing is available for Type A. The carrier rate among the Ashkenazi population is about one in 90.
  • Mucolipidosis Type IV is a rare autosomal recessive disease with a carrier rate of about one in 120 among Ashkenazi Jews. It is a progressive neurological disorder with symptoms beginning in the first year of life. Survival is rare, and the child has severe developmental delays. There is no treatment available.

Other Diseases in Ashkenazi Jews

Torsion dystonia is a muscle-control disorder with an autosomal dominant inheritance pattern, which means it takes only one defective gene to create the possibility of the disease. But only 30 percent of individuals who inherit the mutation will develop the disease. A genetic test can determine whether a person of Ashkenazi Jewish descent has the mutation. Though the frequency of the gene is still uncertain, it occurs in an estimated one in 2,000 Ashkenazi Jewish individuals.

Organizations and Support

For information and support on Genetic Testing, please see the recommended organizations and Spanish-language resources listed below.

Centers for Disease Control and Prevention (CDC) National Office of Public Health Genomics
Website: https://www.cdc.gov/genomics
Address: National Office of Public Health Genomics, CDC
4770 Buford Highway Mailstop K-89
Atlanta, GA 30341
Hotline: 800-CDC-INFO (800-232-4636)
Phone: 770-488-8510
Email: genetics@cdc.gov

Genetic Alliance
Website: https://www.geneticalliance.org
Address: 4301 Connecticut Ave., NW, Suite 404
Washington, DC 20008
Phone: 202-966-5557
Email: info@geneticalliance.org

Hereditary Cancer Center
Website: https://medicine.creighton.edu/hci
Address: Creighton University School of Medicine
2500 California Plaza
Omaha, NE 68178
Hotline: 1-800-648-8133
Phone: 402-280-2634

National Human Genome Research Institute
Website: https://www.genome.gov
Address: Building 31, Room 4B09
31 Center Drive, MSC 2152 9000 Rockville Pike
Bethesda, MD 20892
Phone: 301-402-0911

National Society of Genetic Counselors
Website: https://www.nsgc.org
Address: 401 N. Michigan Avenue
Chicago, IL 60611
Phone: 312-321-6834
Email: nsgc@nsgc.org

Society for Women's Health Research
1025 Connecticut Avenue NW · Suite 1104
Washington, DC 20036
Phone: 202-223-8224
Email: info@swhr.org
Genetic Screening Roadmap
Understanding Genetic Screening and Maternal Health Care Poster

Spanish-language resources

Medline Plus: Genetic Testing
Website: https://www.nlm.nih.gov/medlineplus/spanish/genetictesting.html
Address: Customer Service
8600 Rockville Pike
Bethesda, MD 20894
Email: custserv@nlm.nih.gov

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