Genetic carrier screening tests are used before or during pregnancy to find couples at high risk for having children with certain genetic conditions. They can be very useful, but they’re not perfect. Here’s what you should know about them:

Carrier Screening Basics

Human genes can range in size from only a few hundred letters long, to 2.4 million letters. Typos, or mutations, can happen at any point within a gene, and sometimes cause genetic conditions. For example, cystic fibrosis (CF) is a lifelong condition that causes trouble breathing, frequent infections, and problems with digestion. It’s caused by mutations in the CFTR gene, which is over 189,000 letters long. Geneticists have identified over 1,000 different mutations in CFTR that cause cystic fibrosis. This condition is “autosomal recessive,” which means that you must be born with mutations in both copies of your CFTR gene in order to be affected by the condition (one from Mom, and one from Dad). We know that about 1 in every 25 caucasian people have just one mutation in CFTR. We say these people are “carriers” because they carry a gene mutation, but are not affected by it. If two carriers have a baby together, there is a 1 in 4 chance that the baby will have CF. Now, think about how many Caucasian people you know. If you live in the US (or Canada, or Europe, or Austraila, etc.) I’m guessing it’s probably more than 25. Like, way more than 25. Statistically speaking, you probably know several people who are carriers of cystic fibrosis and don’t know it.

https://en.wikipedia.org/wiki/File:Autorecessive.svg
How autosomal recessive conditions are inherited

If a couple is Caucasian and wants to know if they could have a baby with CF, should we look at all 189,000 letters of both copies of their CFTR genes? That would get expensive really, really fast. So what are we to do? Well, it turns out that in Caucasian people with CF, as many as 70% have at least one copy of one specific mutation called ∆F508 (pronounced delta-F-5-oh-8). If we were to read all 189,000 letters of the gene in all Caucasian people, we’d be spending tons of time and money and getting the same result, ∆F508, most of the time. So our practical solution to this is carrier screening. We take ∆F508 and a group of the other most common mutations, and just test for those. In the CFTR gene, we’ve got a list of 23 common mutations that every screening test should look for, and some labs will add more on top of that. This kind of testing is fast and relatively cheap, so allows us to do the test on just about every Caucasian person who is interested in finding out if they could have a child with CF.

Drawbacks

This method of carrier screening is cost effective, but it’s not perfect. Even the best and biggest screening test is going to miss the carriers of less common or rare mutations.  If a couple’s CF screening tests come back without a mutation, we can tell them that their chance of having an affected baby together is now, say, less than 1 in 100,000 (depending on the detection rate of the test), but it’s not zero. Since there’s no such thing as a no-risk pregnancy, we typically leave “good enough” alone at this point.

If one partner’s test reveals a mutation, and the other partner’s screen is normal, we’re not off the hook just yet. In these cases, we want to be as sure as possible we didn’t miss something, so we’ll order comprehensive gene testing (called “full sequencing”) on the other partner to actually read every letter of the gene. This takes more time, more money, and can be pretty stressful for the couple, especially if the whole process is happening while they’re already pregnant.

What kinds of carrier screening tests are available?

Traditionally, people have been offered carrier screening based on their ethnicity or racial background. Different ethnic groups tend to have higher rates of different genetic conditions, so it makes sense to just offer the tests that are most effective for each person’s background. However, there are a lot of conditions that happen at pretty equal rates across all ethnicities. There are also people who carry conditions that are rare in their own ethnic group, and lots of people who are mixed-race, or don’t fit neatly into pre-determined ethnic categories. To address these issues, more and more labs are offering “pan-ethnic” carrier screens. These screening tests can look for a few key mutations in over 100 genes with a single blood sample or tube of saliva. There’s no standard list of genes that should be on these tests, so each lab picks and chooses the genes they think are most important. As a guiding principle, though, they should all be severe conditions that affect children very early in life. They don’t tend to include genes that might not affect a person until they turn 25.

Options for at risk couples

Carrier testing is the most useful if it is completed before a couple gets pregnant. This gives us plenty of time to complete any follow-up testing that might be needed, and gives them the most options if they are found to be at risk. Some at risk couples may decide not to have children, to adopt, or to use donor eggs or sperm (from a non-carrier, of course). Another option is a process called “preimplantation genetic diagnosis” or PGD. For PGD to take place, the couple undergoes in vitro fertilization (IVF), the resulting embryos are tested for the genetic condition in question, and only embryos found not to be affected are used to attempt a pregnancy. As you can imagine, this is very expensive, and like all IVF attempts, is not always successful.

Couples who decide to go ahead with pregnancy naturally, or those who are already pregnant when they find out they are carriers, have the option of doing prenatal testing (before birth), or postnatal testing (after birth). Because these couples only have a 25% (1 in 4) chance of having an affected child, they will get happy news 75% of the time and won’t have to worry about that condition anymore (this time, at least).

In cases where the condition is confirmed prenatally, the couple may make a very hard and personal decision to end the pregnancy (since some of these conditions are lethal or have no available treatments), or may continue and use the remainder of the pregnancy preparing for what is to come. Many couples appreciate having the opportunity to learn about the condition ahead of time, meet the specialists that will care for their child after birth, and to get in contact with other parents of affected children. If the couple decides to wait to have the child tested when they are born, there can still be great advantages to a speedy diagnosis.

What to ask your doctor

If you are considering having a child or are already pregnant, and think that you would like to have carrier screening, ask your doctor. Here are some things to discuss:

  • Are there any tests recommended for your specific ethnic background?
  • Do they offer the tests themselves, or do you need to see a genetic counselor or other genetic specialist?
  • If they offer pan-ethnic carrier screening, ask if you can have a list of conditions the test includes. If they don’t have a printed list, they should be able to point you to the laboratory’s website for more detailed information on which conditions are screened for.
  • What you might expect to pay out of pocket? Even with insurance some people still have a portion they have to pay themselves.

Other Considerations

Keep in mind that if you or your partner end up needing full sequencing of one or more genes, this can add additional costs, sometimes in the hundreds or thousands of dollars. The labs that do full sequencing tests are few and far between, so you may end up needing to use a lab that is “out of network” which can mean less help from insurance.

Some OB-GYNs order common carrier screening tests on everyone as part of their routine prenatal lab work. So if you are already pregnant and do not want carrier screening, it’s still important to talk to your doctor about what tests they offer and make it clear that you want to opt out.

Another important note: Carrier screening tests are most useful for people who have no family history of the genetic condition in question. People who have a family member with a known genetic condition should see a genetic counselor or geneticist to determine the most appropriate testing for them.

When considering carrier screening, it’s important to think about why you want or don’t want this kind of testing. For some people the stress of the process is more trouble than it’s worth, especially since we can’t ever rule out every known condition. Others feel empowered by having this kind of information ahead of time. Each couple’s situation is different, so take your time to think about what is right for you.


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