Carrier Screening 101

Be Prepared for Pregnancy

At least 1 in 3 individuals who are of Jewish ancestry (Ashkenazi, Sephardi, or Mizrahi) is a carrier for at least one Jewish genetic disease. Carriers of these diseases exhibit no symptoms of that disease, and usually do not have a family history of the disease. A carrier will only know of his or her status after a screening, or if he or she has a child who is affected with the disease.

Genetic testing for conditions that occur more frequently in the various Jewish populations is available. These types of diseases are caused by a mutation in the gene that has been inherited among many people of the population (“founder mutations”). A mutation means that the gene is altered and, as a result, does not work properly. When an individual has a mutation in either of his or her 2 inherited genes for a single disorder, that person is said to be a “carrier.” If both members of a couple are carriers of the same disease, there is a 25% chance they both can pass down their mutations to their child—in that case, the child would be affected with the disease. This pattern of inheritance is called “autosomal recessive.”

It’s not Just Tay-Sachs Anymore!

Many of you may have heard of Tay-Sachs disease. With the introduction of community screening programs in the 1970s and private testing at physician’s offices, Tay-Sachs disease has been nearly eradicated in the Ashkenazi Jewish population. Today, more non-Jewish babies are born with this condition than are Jewish babies. Over the past several decades, other diseases have been identified, that, like Tay-Sachs, tend to be more common among the Jewish population and can be screened for carrier status. All of these conditions that can affect the offspring of carrier couples are serious diseases that can be fatal or have life-threatening symptoms. Each disease has a unique carrier frequency, effect on daily living, lifespan, and possible treatment (if any). There are many labs that offer genetic testing for many of these conditions.With advances in gene discovery and technology, additional diseases that appear to be more common in the Jewish population continue to be identified.

 Why us?

The Jews of Eastern Europe (“Ashkenazi Jews”) have lived in small insular communities for hundreds of years. Mutations in genes were present in these communities, but were not common. The communities changed over time; there was migration outside, isolation, and a decrease in size. As a result, the mutations that had been rare earlier now became more prevalent, and a higher percentage of the population became carriers. This phenomenon is known as the “founder effect.” Sephardi and Mizrahi Jewish populations are more genetically diverse than Ashkenazi Jews, however, they still have genetic diseases which are more common, yet are unique to their own populations.

Jews are not the only population to have high carrier frequencies for this reason. For example, sickle cell disease tends to affect African-Americans, beta thalassemia affects Mediterranean populations, and Tay-Sachs disease is also common among the French Canadian, Irish, and Louisiana Cajun populations.

How one identifies with their religion does not define their ancestry. An individual does not need to practice Judaism to be considered Jewish. If an individual has at least one grandparent who descended from an Ashkenazi, Sephardi, or Mizrahi Jew, that person is at risk of being a carrier for a Jewish genetic disease. Therefore, these individuals should be screened.

What else needs to be addressed?

A referral to a geneticist or genetic counselor can be made for testing for other common conditions such as hereditary breast and ovarian cancer, hemophilia, and rare genetic diseases which may run in one’s own family.

How to Get Screened

Jewish carrier screening is generally done with a simple blood draw. The blood is sent to an accredited laboratory and DNA is extracted. Specialized genetic tests are performed to look for mutations (changes) in each of the genes. For Tay-Sachs carrier screening, an additional test is done that is called the HexA enzyme assay. This test looks at levels of the specific enzyme that is reduced in Tay-Sachs carriers and deficient in babies with Tay-Sachs. Please note that some labs will allow you to send in a saliva sample, but Tay Sachs enzyme testing cannot be performed using saliva.

A report with the results is written, and indicates whether or not the individual is a carrier for any of the diseases. The results of this testing are very accurate, however there is always a “residual risk” to be a carrier, which will be written on the report.

It is very important that a genetics professional or trained physician reads the results carefully and gives a copy of the report to the patient only. It is up to the individual to decide whether or not this information should be shared with family members. Of course, we encourage those with positive results to share because direct relatives of an individual with a mutation have a higher chance of being a carrier than those in the general population. As the testing panel may expand in the future, it is important for the individual to keep his or her report for updating.

Reproductive Options for Carrier Couples

If both members of a couple are found to be carriers for the same disease, there are several options for family planning. Some couples may choose to get pregnant and then find out if the fetus is affected (with the option of terminating the pregnancy). Others would rather avoid getting pregnant with an affected fetus from the very beginning. Consultation with a rabbi, spiritual leader or mental health professional may be appropriate for those who need help deciding which option is best for them. Here is some information on each of the options:

Before a Pregnancy: Not leaving things up to chance

  1. Preimplantation Genetic Diagnosis (PGD)
    PGD is performed as a part of an in- vitro Fertilization (IVF) cycle. Multiple eggs are produced by the woman through rigorous hormone stimulation. They are then retrieved from her ovaries and fertilized with her partner’s sperm in a laboratory setting. Once the embryos that are produced from this union reach the eight-cell stage, one of those cells is extracted from each embryo. That one cell is tested for the disease in question. If the cell shows to have 2 mutations (affected with the disease), the embryo from which it came will not be implanted in the woman. Only embryos that are not affected will be implanted. PGD is an excellent option for carrier couples because it is a means to circumvent the potential issues that may arise once a carrier couple is already pregnant. However, diagnosis by PGD is not perfect. Fetal testing via CVS or amniocentesis (see below) is recommended in conjunction with PGD. The cost of IVF with PGD is high, varies from center to center, and not all health insurance plans will cover the costs. A genetic counselor or OB/GYN can make referrals to specialists in assisted reproductive technology, such as PGD.  Click to watch a short video on pre-implantation genetic diagnosis at our online education series and then register at the site to access the full PGD lesson, including a webinar from Dr. Harry Lieman, PJGH Liaison for Fertility and Reproductive Technologies.
  2. Egg or Sperm Donation
    If both members of a couple are carriers, another option is to use the gametes (i.e., egg or sperm) of only one of the two. Individuals who choose this option use egg or sperm donors that have been screened for the disease in question and are found not to be carriers.
  3. Adoption
    Couples who wish to have a child, but are both carriers for a fatal disease, may decide to adopt.

During a Pregnancy: Ways to test the fetus to see if it is affected (prenatal diagnosis)

  1. Chorionic Villus Sampling (CVS)
    In this medical procedure, a small sample of the placentais extracted through the woman’s abdomen or cervix with a thin needle, under ultrasound guidance. This sample is sent to a lab, where fetal testing is performed. The results of this test will tell the couple if the fetus is affected with the disease in question. CVS is performed between 10-13 weeks of pregnancy.
  2. Amniocentesis
    In this medical procedure, a small sample of amniotic fluidis extracted through the woman’s abdomen with a thin needle, under ultrasound guidance. Like a CVS, this sample is sent to a lab, where fetal testing is performed. The results of this test will tell the couple if the fetus is affected. This procedure is performed between 16-22 weeks of pregnancy.

Both CVS and amniocentesis have a slight risk of miscarriage (about 1 in 500). It is recommended that couples who choose to have either one of these procedures have it done in conjunction with genetic counseling in an experienced center.