Other Genetic Diseases

Signs and Symptoms

Depending on your family history, ethnicity and heritage, your developing baby may be at risk for one of the following genetic conditions:

1. Canavan Disease — This condition is most common in people of Ashkenazi Jewish ancestry, with a carrier incidence of 1 in 40. Canavan disease is a central nervous system disease that is usually fatal in childhood, with a few people surviving to adulthood. This disease is the result of a substance that destroys the central nervous system over time. There is presently no effective treatment for Canavan disease.

2. Fragile X Syndrome — The Fragile X syndrome is not specific to a certain ethnic background. It is an inherited condition that can cause a range of intellectual and behavioral problems, from learning disabilities to mental retardation to autism. While Fragile X syndrome tends to be more severe in boys, it occurs in both males or females. It can be passed on to family members by individuals who have no signs of the syndrome. Review of your family history with a genetic counselor may help determine if Fragile X carrier testing is indicated.

3. Sickle Cell Disease — This condition is most common in persons of African-American, African, Mediterranean, Hispanic and South American ancestry, with the carrier risk ranging from 1/10 to 1/40, depending on your ethnic background. Sickle cell disease is caused by a variant hemoglobin that changes the shape of the red blood cells. This causes anemia, severe pain, a tendency toward infection, and other serious health problems. Frequent blood transfusions and infection preventing antibiotics are available treatment. UCSF doctors were the first to develop a prenatal test for sickle cell anemia.

4. Tay Sachs Disease — People of both Ashkenazi Jewish and French Canadian ancestry have the greatest chance of being carriers of Tay Sachs disease, about 1/30 versus 1/250 in the general population. The disease results from a build up of certain substances in the brain, and is fatal in early childhood. There is presently no effective treatment for Tay Sachs disease.

5. Thalassemia — Individuals of Mediterranean, Southeast Asian and African ancestry have the greatest chance — 1 in 3 and 1 in 30, respectively — of being carriers for thalassemia. In general, this group of blood disorders affects a person's ability to produce hemoglobins, the protein in our blood that carries oxygen and nutrients to all parts of the body. In severe cases, children with thalassemia may not survive. Others have anemia, bone growth problems and liver and spleen involvement. Blood transfusions may be needed for treatment. UCSF doctors were the first to develop a prenatal test for thalassemia.

Some genetic disorders are more common in certain ethnic groups. People who carry genes for these disorders may not have symptoms. However, if both parents are carriers of the same abnormal gene, the chance of having an affected child is 1 in 4, or 25 percent, for each pregnancy. A special blood test, called a carrier test, may be able to tell if you carry such a trait.

Diagnosis

To determine if you or your partner are a carrier of a genetic disease, a blood test can be performed. Other diagnostic tests can be performed to determine if your fetus has a genetic disease.

Carrier Testing

Carrier testing is a blood test that can determine if you carry one of the two abnormal genes that can produce a specific recessive disorder. The number of conditions for which testing is possible is rapidly increasing, although its not yet possible to test for all genetic conditions.

The implications of having a genetic disorder can vary. Some disorders cause severe problems, whereas others may be mild. The decision to have carrier testing is a personal one made after carefully considering the options.

Factors to Consider

If you are considering carrier testing, here are some factors to consider:

• Family History -- If someone in your family has a genetic disorder, you may have an increased chance of being a carrier yourself. It is a good idea to speak with your relatives to determine if there are genetic disorders that are known to run in your family. This information can then be discussed with your physician or a genetic counselor to determine your chance of being a carrier. Genetic tests may exist to determine carrier status, although this will not always be possible.

• Ethnic Background -- Some genetic disorders are particularly common among those of a specific racial or ethnic background. For example, sickle cell disease is found most often among persons of African ancestry; Tay-Sachs disease most often in persons of Ashkenazi Jewish ancestry; and Cystic fibrosis among persons who are Caucasian.

Information can be provided for the more common disorders for which carrier screening is currently available. This list will likely expand in the coming years. Please speak with your physician or genetic counselor for additional information about these disorders or others you may wish to know about.

About Testing Results

If you are interested in carrier testing, there are several issues to consider:

• Detection Rate of Carrier Testing -- Although some genetic tests can identify all carriers, others identify only some of the genes that cause a specific disease. If you are identified as a carrier of a genetic disorder, the results are considered highly accurate. However, if you have a "negative" result, there is still a chance that you could carry an abnormality not detected by current testing. For some carrier tests, a negative result can lower the risk of being a carrier but cannot completely eliminate this risk.

• Accuracy of Carrier Testing May Depend on Your Ethnicity -- Carrier testing usually identifies the changes in a gene that are found most commonly in a specific ethnic group. For example, cystic fibrosis carrier testing can identify 85 percent of the genetic changes that cause disease in persons of Northern European ancestry, but only about 30 percent of changes in persons of Asian-American ancestry. Your ethnicity is an important determinant in the ability to determine carrier status.

• Health Insurance Coverage -- Your health insurance may cover genetic carrier testing. However, if it does not, you may have to pay for genetic testing yourself. Before testing, you may want to contact your insurance company.

• Information Gained -- If you and your partner are found to be carriers of an autosomal recessive genetic disease, you have a 25 percent chance of having an affected child. It is possible to test your baby for the genetic disease before he or she is born through prenatal diagnostic testing. The information can also be used to prepare for the birth of an affected child and adoption is always an option for couples that may not feel capable of caring for an affected child. If you and your partners are found not to be carriers of one of these inherited disorders, it greatly reduces your risk of having a child with that specific disease.

• When to Test -- Some types of genetic testing may be complicated and may take several weeks for results. If you are interested in carrier testing, it is important to be tested as early as possible, especially if you are pregnant. It is ideal to do carrier testing before pregnancy.

Diagnostic Tests

• Amniocentesis -- Amniocentesis is used most commonly to identify chromosomal problems in a fetus. When the fetus is known to be at risk, it can detect other genetic diseases like cystic fibrosis, Tay-Sachs disease and sickle cell disease. An amniocentesis procedure for genetic testing is typically performed between 15 and 20 weeks of pregnancy. Under ultrasound guidance, a needle is inserted through the abdomen to remove a small amount of amniotic fluid. The cells from the fluid are then cultured and a karyotype analysis -- analysis of the chromosomal make-up of the cells -- is performed. It takes about two weeks to receive the results of the test.

  Amniocentesis detects most chromosomal disorders with a high degree of accuracy. Testing for other genetic diseases, such as Tay-Sachs disease, is not routinely performed but can be detected through specialized testing if the fetus is known to be at risk. Testing for neural tube defects, like spina bifida, also is performed on the amniotic fluid. There is a small risk of miscarriage as a result of amniocentesis -- 1 in 100 or less. Miscarriage rates for procedures performed at UCSF Medical Center are less than 1 in 350.

• Chorionic Villus Sampling (CVS) -- Like amniocentesis, chorionic villus sampling is used most commonly to identify chromosomal problems. It can detect other genetic diseases like cystic fibrosis, Tay-Sachs disease and sickle cell disease in at-risk fetuses. An advantage of CVS compared to amniocentesis is that it is done much earlier in pregnancy, at 10 to 12 weeks rather than 15 to 20 weeks.

  The CVS procedure involves removing a tiny piece of tissue from the placenta. Under ultrasound guidance, the tissue is obtained with a needle through the abdomen or a catheter inserted through the cervix. The tissue is then cultured and a karyotype analysis -- analysis of the chromosomal make-up of the cells -- is performed. It takes about two weeks to receive the results.

  The advantage of CVS over amniocentesis is that the test is performed much earlier in pregnancy, so results are typically available by the end of the third month. A disadvantage is that spinal cord defects cannot be detected. Expanded alpha fetoprotein (AFP) blood testing or ultrasound can be performed later in the pregnancy to screen for spinal cord defects.

  There is a small risk of miscarriage as a result of CVS - about 1 in 100 or less. Miscarriage rates for procedures performed at UCSF Medical Center are less than 1 in 200.

• Ultrasound -- The primary purpose of ultrasound is to determine the status of a pregnancy -- the due date, size of the fetus and if there are multiple fetuses. When performed by experienced health professionals, ultrasound also provides some information about possible birth defects. All patients at UCSF Medical Center undergo a comprehensive ultrasound examination before any invasive tests are performed. Results of the ultrasound are explained at the time of the visit.

  In some patients, an ultrasound raises concern of a possible abnormality in the fetus. We have extensive experience in performing and interpreting ultrasounds in pregnancy.

Treatment

If you have positive results on a screening test, we recommend that you discuss this with your own doctor and a genetic counselor. Options for further diagnostic testing will be explained. The decision as to whether to have invasive genetic testing is up to you.

If a diagnostic test finds a genetic abnormality, the significance of such results should be discussed with experts familiar with the condition, including a medical geneticist and a genetic counselor, as well as your own doctor. Medical geneticists and genetic counselors are available at the UCSF Prenatal Diagnosis Center. Referrals and support information are available for all decisions.