Case History
Cassie is 37 years old, of Middle Eastern ancestry, and 16 weeks pregnant. She had some spotting in her first trimester and only recently realized that she is pregnant. The father of the baby is not involved, but Cassie knows his family was Caucasian, of Northern European ancestry. Cassie learned about carrier screening from a friend and asks whether she should undergo testing. She is anxious about the health of the baby and her ability to raise a child with special needs as a single mother. She is interested in noninvasive tests that can give her more precise information about severe conditions affecting the pregnancy. After discussing aneuploidy screening, you present options for carrier screening.
Question
You want to review benefits and limitations of ECS with Cassie. However, you have limited time, and you don’t want to overwhelm the patient with technical details. Review the list of benefits and limitations of ECS with Cassie's motivations, goals and medical history in mind.
Select two benefits and two limitations that you feel are most relevant to discuss with Cassie.
Answer Summary
All of the benefits and limitations should be considered, but some will be more relevant given the patient's specific situation, motivations and expectations.
Primary benefits for Cassie
Assesses a larger number of conditions. Cassie shared that she is concerned about rare, severe conditions. ECS screens for a larger number of conditions than ethnicity-based screening. Some labs will provide a list of conditions categorized by severity and treatability so you can select the most comprehensive test for the types of conditions Cassie is concerned about.
Certain panels have greater sensitivity for rare variants. In addition to screening for a larger number of conditions, certain ECS platforms have greater sensitivity for rare variants. In Cassie's case this is important because there may be less data available on disease-causing variants in the Middle Eastern population. Such rare variants may not be represented on a panel that targets specific common variants.
See Dig Deeper – Variant vs. Sequencing Panels
Primary limitations for Cassie
Typically requires testing of both parents for the most informative results. If Cassie was found to be a carrier of an autosomal recessive condition, the risk to the baby depends on the father’s carrier status. When the father is not available, the baby’s risk can sometimes be estimated using carrier rates for the condition in the general population. This is true for all types of carrier screening. However, risks for the baby may be more difficult to calculate for some conditions included on ECS panels. Carrier rates may not be known for very rare conditions, or for certain ethnic groups. While invasive testing is an option, there may not be enough data to accurately weigh the procedural risks of miscarriage against the likelihood that the baby is affected. In addition, many labs will not perform prenatal diagnosis unless both parental variants are known.
Residual risk may be more difficult to calculate. While no screening can completely rule out carrier status, laboratories can often calculate the chance that a patient is still a carrier given her negative screen. However, there may not be enough data to calculate residual risk for the very rare conditions included on ECS panels. In addition, residual risk estimates may not be available for certain ethnic groups. Cassie wants to learn about her risk for serious conditions, but she is already anxious about uncertainties in her pregnancy. She should understand that precise risk figures may not be possible for all of the conditions included on ECS.
For a patient like Cassie, who has no family history of a specific disease, carrier screening may provide sufficient reassurance. However, when a patient has a family history of a disease a different testing strategy may be more appropriate, such as targeted familial mutation testing or full gene sequencing.
Carrier screening is not the right choice for every patient
For a patient who is already anxious about uncertainty in the pregnancy and looking for definitive risk information, the risks of ECS may outweigh the benefits. As with all prenatal genetic screening, the risks, benefits and limitations of ECS should be reviewed with the patient as part of pre-test counseling so she can make an informed decision about her preferred evaluation plan. If Cassie declines carrier screening, she can be counseled about her risk for having a child with a severe condition based on general population data, family history, and (if elected) results from other prenatal tests, such as aneuploidy screening and ultrasound, as well as informed about newborn screening that will occur at birth.