What you should know about expanded genetic carrier screening?

A recent study published in the Journal of American Medical Association (JAMA), looked into the possibility of routine screening of all couples for a single recessive gene carrier status. This is irrespective of their family history.

Between 2012 and 2015 more than 300,000 individual were tested for 94 profound or severe genetic conditions. They observed that around 94 to 392 fetuses for every 100,000 would have at least one of these conditions. This varied for different ethnic groups. The study highlighted that by using the expanded carrier screening panels, many more fetuses are likely to be identified than with the current screening guidelines.

The challenge is that the couples have to make a difficult decision. They have to decide if ending the pregnancy or having a child who may have a recessive single gene defect. This has consequences for the child, parents and healthcare systems. This study has started a new dialogue. It will be important to confirm these findings in larger studies before such tests are available.

In my opinion, the test should be a part of preconception counselling or services. This will inform the couples of the risk and prevent the birth of children who may have these genetic conditions. There has been a progression in genetic diagnostic testing since genome sequencing. This has expanded the number of conditions that specialists can diagnose.

This progression also increased the diagnostic efficiency and significantly dropped the costs. Expanded carrier screening for recessive conditions was first made available in 2009. It is noteworthy that one in four individuals are carriers of at least one of the ninety-six serious/profound single gene recessive conditions. To inherit a recessive condition, both parents should be carriers of the faulty gene.

The future of expanded genetic carrier screening

In such cases, the chance of the child inheriting the condition is almost one in four. Hence, most parents who are carriers will be offered preimplantation genetic diagnosis or PGD. This will prevent the transmission of the genetic condition to the next generation. Usually, such couples either have had an affected child or have a family history. Preimplantation genetic diagnosis or PGD involves couples going through IVF treatment.

When the embryos have been created, they are biopsied and screened for the faulty gene. Only those embryos that do not carry the faulty gene are then transferred or frozen for future use. The current practice is to screen the pregnant mother for certain genetic conditions. These screening methods are based on the prevalence of the genetic conditions. In particular, ethnic groups or family history. Your specialist will assess at the initial antenatal visits for any extra screening.

I think that the expanded genetic carrier screening is offered to couples as part of the preconception counselling rather antenatal (or prenatal) care. We are in an information age and deal with billions of pieces of information each day.

In my experience, most potential parents try to avoid any genetic conditions that can affect the next generation. When counselling patients, I am commonly asked if the unborn child will be absolutely healthy and free of genetic conditions. This will never be possible, but there is a potential to reduce the risk of a child being born with recessive genetic conditions.

Obviously, the consequence will be the rise in the number of healthy couples with no family history seeking PGD. They prefer this process instead of what would have been a natural conception. As PGD involves an IVF treatment, couples will risk many complications of IVF treatment. This may avoid the long term risk of having a child affected with the single gene recessive condition. Besides the risks of IVF, this also causes a sense of anxiety and referral to clinical geneticists.

Currently, some of the European fertility clinics are using these expanded carrier screening tools. In particular, screening egg donors before matching to the potential egg recipient couples. In such fertility clinics, the egg donor has a blood test. Specialists control her for few hundred autosomal recessive genetic conditions.

If she is a carrier, then the partner of the egg recipient lady undergoes the test. This is necessary to confirm that he is not the carrier of the any of these genetic conditions to which the donor has been screened. If the partner of the egg recipient and the egg donor have a positive screen for the same condition, then specialists match the couple to a different egg donor.

Some of the clinics are offering these services as a routine practice, whereas others are considering on a case by case basis. In the UK, such practice of screening egg donors using expanded genetic carrier screening does not exist. This is because there are fewer donors available. By screening the egg donors, the number of available donors will be even more limited.

This is an interesting study that has opened a new chapter of routine expanded genetic carrier screening of the pregnant mothers. I wait for larger studies to explore this in greater depth before offering this to our patients as part of preconception counselling. I think this may be the start of new era in our quest of a perfectly healthy child.