Nondisclosure and Exclusion Testing

Discovering you have a family history of an inherited neurodegenerative condition and a genetic variant has been identified for the condition can be a double-edged sword. On one hand, it can raise awareness and encourage proactive health measures. On the other, it can spark anxiety and uncertainty about personal risk. Genetic testing provides valuable insights, but the decision to pursue testing is complex. Some individuals want to get genetic testing performed to know if they inherited the genetic variant whereas other do not want to know this information.

Nevertheless, a person that doesn’t want to know their status may still want to reduce the possibility of passing on the inherited neurodegenerative condition to future children. For these individuals, they may have the option to do non-disclosure or exclusion preimplantation genetic testing for monogenic disorders (PGT-M). In this blog, we'll delve into the considerations surrounding non-disclosure and exclusion PGT-M testing.

Genetic Testing

Genetic testing can provide a clearer picture of your chance of developing symptoms of the inherited neurodegenerative condition. Identifying a specific variant can enable early monitoring, lifestyle adjustments, and potential interventions. Moreover, genetic testing can be empowering for family planning decisions, offering the opportunity to test embryos or pregnancies for the genetic variant.

Embarking on genetic testing is a personal decision influenced by various factors. Some individuals are anxious about not knowing their genetic status and want to take control of their health journey. Others, however, may experience anxiety too but because of the possible uncertain outcomes surrounding a neurodegenerative condition. There is no right answer of whether or not to have genetic testing for the inherited neurodegenerative condition.

PGT-M Testing: Exploring the Concepts of Non-disclosure and Exclusion Testing

Non-disclosure or exclusion PGT-M testing testing approaches enables individuals to have their embryos screened for the genetic variant without being informed about their status. This way, individuals can transfer embryos not at risk of inheriting the familial genetic variant. Non-disclosure and exclusion testing are two separate approaches with the same goal. If you’d like to learn more about PGT-M, please check out this informational page as this blog post will skip reviewing the PGT-M process.

Non-Disclosure:

With this approach, the genetic status of the individual at risk is known by the laboratory performing the PGT-M. However, the individual has signed consents to ensure that the lab does not reveal this information to the individual. The benefit of this approach is that only embryos that have the genetic variant are excluded from transfer. However, the limitation of this approach is that it is possible the individual’s genetic status is accidentally revealed.

Exclusion:

With this approach, the genetic status of the individual is NOT known by the laboratory. Instead, the lab determines which gene copy the relative with the inherited neurodegenerative condition passed on to the individual. For any embryo that inherited that gene copy, the embryo is excluded from transfer.

The limitation of this is that the gene copy could be normal, and embryos may be excluded when they otherwise are not expected to develop symptoms related to the neurodegenerative condition. The lab is not checking to see if the gene copy has the variant, only who the gene copy was inherited from. The benefit of this approach is that the genetic status of the individual is not known to any party.

To better explain exclusion PGT-M testing, we can take a look at the above picture. It shows a father, who has the neurodegenerative condition, a mother, and son. The son does not know if he inherited the genetic variant from his father. The two green sticks below the father are suppose to represent two genes. For most of our genes, we have two copies: one we inherit from our fathers and the other from our mothers. The son inherited one green gene from his father and the other blue gene from his mother. It is not known if he inherited the green gene with the genetic variant or the normal green gene from his father. His father has one gene with the variant and one gene without the variant. He has a 50% chance to pass on the one with the variant to his son but a 50% chance to pass on the one without the variant.

If the son pursues exclusion PGT-M testing, then any embryo that inherits the green gene copy will be assumed as having the genetic variant because the green gene copy comes from the son’s father, who has the condition. By making this assumption, it allows the son to remain unaware of his genetic status while also excluding any embryo that MIGHT have the genetic variant related to the inherited neurodegenerative condition.

Key Considerations

Comfort with the Unknown: With exclusion testing, there is the possibility of excluding embryos for transfer that may otherwise not have the genetic variant. Some people may find this difficult because they may wonder if those embryos actually inherited the normal copy of the gene and could be transferred.

Determination: Few labs and clinics offer the option of nondisclosure testing given the ethical concerns of one party knowing the genetic status of the individual, while the individual does not have this information. This paradigm is not common in the western medical system given the intense desire for patients to have all their medical information accessible to them. The option of nondisclosure may require more advocating.

Future: While you may not want to know your status at this time, if it comes a time that there are no embryos available to transfer or a change in mind of knowing one’s status, then this would require a new PGT-M test design, possible need to rebiopsy and retest embryos, and an increase in cost and time.

Conclusion

Family history of an inherited neurodegenerative condition can be a source of concern and curiosity. Genetic testing offers insight into one's risk, but it's not a decision to be taken lightly. For those concerned by their genetic risk and possibility of passing it on to future generations but are hesitant to know the specifics, non-disclosure/exclusion PGT-M testing can be an option worth exploring. However, like any decision, it requires careful consideration of emotional, ethical, and medical factors.