A 25-year-old female, comes to our office for her well-woman examination. We asked her if, and when she is interested in getting pregnant. She said she would like to try to get pregnant about a year since a current day. Her mother has told her that because she is of Ashkenazi Jewish descent she “needs to get tested.” She has a history of regular menses and is sexually active in a mutually monogamous heterosexual relationship. She has never had any sexually transmitted infections and has had normal pap smears.
Genetic Preconception Counseling
Preconception counseling is important to optimize a patient’s/couple’s health and reduce or eliminate risk before conception as well as to give information regarding issues that affect them on an individual level. Providing genetic preconception counseling is vital to allow time for information gathering that can positively affect a future pregnancy. Family planning and contraception are important discussions with each visit for reproductive-age women.
Once a woman or a couple have made the decision to consider pregnancy, a thorough history allows the preconception conversation to be tailored to specific issues. There is a recommendation that eight different areas be evaluated:
Environmental toxins and teratogens,
Nutrition and folic acid,
Substance abuse, including tobacco and alcohol,
Medical conditions and medications,
Infectious diseases and vaccinations,
Psychosocial issues including screening for intimate partner violence.
Genetic screening and evaluation of risks in the preconception time allow for nondirective conversations that may affect pregnancy decisions. Preconception planning allows for adequate time to receive test results and obtain follow-up testing, and also allows an opportunity for the couple to make decisions regarding Assisted Reproductive Technologies (ART) and Preimplantation Genetic Diagnosis (PGD).
The background population risk for a major birth defect or genetic problem is 2-5%. There are specific genetic disorders that are more prevalent in the Ashkenazi Jewish population.
The Ashkenazi Jewish genetic disorders are single-gene autosomal recessive in nature. If both members of the couple are carriers for the same disease, then every time they conceive, the chance of having an affected offspring is 25%. The offspring also has a 50% chance of being just a carrier and there is a 25% chance of the offspring not being affected and not being a carrier. Currently, 19 different diseases can be screened specifically in the Ashkenazi Jewish population. These diseases can occur at a higher prevalence in this population (e.g., Tay Sachs disease) or occur almost exclusively in Ashkenazi Jews (e.g., Familial Dysautonomia). If only one partner is of Ashkenazi Jewish descent, meaning that they have one grandparent who is Ashkenazi Jewish, then that person should be offered screening first. Once the carrier status is determined, the partner should be screened. This is called sequential screening. If timing is important, then simultaneous screening of both partners can be done.
When a patient is found to be a carrier, her partner should then be screened for the specific disease for which she is a carrier. The risk that the infant will be affected is significantly reduced, but not zero. There is a residual risk that although the parent tested negative, he may still be a carrier as he could have a mutation not screened for by the test. The residual risk is different for each disease and ethnic group.
Given that there are 19 conditions recommended, there is a 1 in 3 to a 1 in 4 chance that any one individual of Ashkenazi Jewish descent will test positive for at least one of the conditions. Detection rate and carrier frequency are not as well known in non-Jewish populations (except for Tay Sachs disease and cystic fibrosis). This may make it difficult to determine the couple’s numerical risk of having a child with one of these other disorders, especially if the partner is unavailable or chooses not to be screened.
There are a number of screening tests available commercially. Through advances in technology and efficiencies in sequencing, many conditions can be looked for simultaneously. Some of the screening kits can assess for over 250 different conditions. Many of these conditions are not currently recommended for screening by any medical society. Some conditions may have variable presentations and population risks may be unknown. As the technology continues to improve, this number will likely expand.
It is important to keep in mind that when using expanded carrier screening that has over 100 diseases, it is likely that an individual will be positive for at least 1-3 of these conditions. Genetic counseling should be offered for the couple after testing is back if both are found to be carriers of a genetic condition. It is also important to counsel a patient on potential negative consequences of testing.
Currently, genetic screening is offering to those of Ashkenazi Jewish descent for Canavan disease, Familial Dysautonomia, Tay Sachs disease, spinal muscular atrophy, and cystic fibrosis (the last 2 are recommended for everyone considering pregnancy). However, there are some experts who recommend a more complete list be offered, including Bloom syndrome, Familial hyperinsulinism, Fanconi Anemia C, Gaucher Disease, Glycogen Storage Disease type 1, Joubert Syndrome 2, Maple Syrup Urine Disease, Mucolipidosis Type IV, Niemann-Pick Disease, Usher Syndrome, and Walker Warburg syndrome.
Genetic screening should be offered to any woman considering pregnancy and that acceptable screening strategies be based either on risk alone or by offering expanded carrier/pan-ethnic screening. It is important to have pre- and post-test counseling. Pretest counseling needs to include risks and limitations in addition to the benefits of the testing. It is not practical to discuss each individual condition, but literature should be available about specific conditions as requested by patients. Discussion should include that risks may not be calculable, especially if one partner is of a different ethnicity. Screening does not preclude neonatal testing (such as newborn screening), and conversely, neonatal testing does not eliminate the need to screen a woman considering another pregnancy who has not been screened.
Ask all reproductive-age women their pregnancy desires in order to reduce or eliminate risk and to gather information, including genetic screening, needed for a healthy pregnancy,
Carrier screening and counseling ideally should be performed before pregnancy, and genetic screening should be offered to any woman considering pregnancy,
Acceptable screening strategies can be based either on history-assessed risk or by offering expanded carrier/panethnic screening with appropriate pre- and post-test counseling,
Genetic screening is recommended to those of Ashkenazi Jewish descent for Canavan disease, familial dysautonomia, Tay Sachs disease, spinal muscular atrophy, and cystic fibrosis (the last two are recommended for everyone considering pregnancy),
However, there are some who recommend a more complete list.