Carrier screening has transformed dramatically since its origins in the 1970s. Early programs relied on enzyme-based methods targeting specific populations, most notably Tay-Sachs disease screening in the Ashkenazi Jewish community (Bajaj et al., 2014). By the late 1990s, molecular testing for single genes, such as CFTR, ushered in the first recommendation for pan-ethnic carrier screening (Bajaj et al., 2014). Today, next-generation sequencing and other genomic technologies allow simultaneous screening for hundreds of conditions, ushering in an era of unprecedented scope and information.

Traditionally, carriers were described as “silent” — individuals who harbor a single pathogenic variant but remain unaffected. Within this framework, the central purpose of carrier screening was reproductive risk assessment to help couples understand the likelihood of having children with certain genetic conditions. However, decades of data have shifted this paradigm. We now recognize that carriers are not always asymptomatic. Certain heterozygous individuals may exhibit clinical manifestations, ranging from mild features to serious health complications. This knowledge challenges long-standing assumptions and compels us to rethink both the intent and the scope of carrier screening.

Recent Natera-funded research has highlighted maternal health implications of carrier status during pregnancy, as well as health risks for carriers of specific conditions such as Alport syndrome and familial hypercholesterolemia (Souter et al., 2025; Souter et al., 2024; Souter et al., 2023). In a 14-condition carrier screening panel, at least six of the conditions have well-described carrier manifestations, including Duchenne/Becker muscular dystrophy, cystic fibrosis, fragile X syndrome, etc. When considering much larger carrier screening panels, numerous possible health risks could be flagged for heterozygotes, each with a potentially different level of risk and management options. Recognizing these manifestations can provide valuable insights for personal health management, potentially enabling proactive monitoring, earlier interventions and more informed medical decision-making.

Despite these emerging insights, professional society guidelines have been limited in addressing carrier manifestations. The American College of Obstetricians and Gynecologists’s most recent Committee Opinion on carrier screening acknowledges that carriers are “typically” asymptomatic but stops short of addressing the growing body of evidence on health risks to heterozygotes (ACOG Committee Opinion, 2017). ACMG’s Practice Resource mentions the possibility of manifesting heterozygotes, which should be discussed in pre-test counseling (Gregg et al., 2021). NSGC’s Expanded Carrier Screening Guidelines further discuss health risks for heterozygotes and recommend that patients should be aware of this possibility during informed consent (Sagaser et al., 2023). However, these publications lack guidance on what body of evidence is enough to mention health risks, how clinicians should discuss risks in a post-test setting, or how to manage patients when such risks are identified. 

In practice, this gap creates challenges. Carrier screening panels are often ordered by non-genetics providers, including obstetricians, gynecologists, maternal-fetal medicine specialists, reproductive endocrinologists, etc. Many lack specialized training to interpret nuanced results, and patients may be presented with findings without adequate pretest counseling or posttest support. Genetic counselors, already stretched thin, may only become involved after results are reported. This leads to inconsistent patient experience and uncertainty about who is responsible for follow-up care.

As carrier screening evolves, so too do the ethical considerations surrounding its use:

• Pre- and posttest counseling gaps: Many patients are not aware of the possibility of incidental findings on carrier screening that may affect their own health.
• Equity concerns: Expanded panels are not offered uniformly across populations, and access to genetic counseling and educational resources remains uneven.
• Clinical responsibility: When results suggest a carrier may be at risk, who assumes responsibility for long-term monitoring — ordering providers, primary care or subspecialists?
• Burden on resources: Larger panels increase result complexity, stretching already limited counseling capacity.
• Interpretation of evidence: The penetrance of carrier-associated health risks is often uncertain. At what threshold of evidence should we counsel patients about possible manifestations?
• Psychosocial impact: Incidental personal health information may provoke anxiety, particularly when the risks are rare or poorly defined.  

Professional societies have begun to acknowledge these complexities, but consensus on best practices to address these considerations has yet to emerge.

For the genetics community, it is no longer sufficient to treat carrier screening exclusively as a reproductive tool. The information it yields has the potential to inform not only family planning decisions but also personal health management. This shift raises difficult but necessary questions. Should carrier screening be reframed, or even renamed, to better reflect its dual role? Do we need tiered panel options including one limited to reproductive risk and another that includes conditions with known carrier health implications? How do we balance transparency and patient autonomy with the risk of overwhelming individuals with uncertain or rare findings? Who is responsible for long-term follow-up and patient care once health-relevant findings are identified?

At Natera, we recognize that the evolving understanding of carrier health implications raises complex scientific, ethical and clinical questions. While carrier screening was never designed to assess personal health risk, these findings are reshaping how we interpret and use genetic information on a population health level and the conversation is only just beginning. As genetic counselors, we are uniquely positioned to lead these discussions, translating emerging data into responsible patient care and informed practice. Natera is committed to supporting clinicians and patients through this transition by providing reliable data and educational resources. 

Your expertise helps shape better testing and reporting. As part of our ongoing work to understand how carrier manifestations affect carrier screening reporting and counseling, Natera is collecting feedback and short case examples from the GC community. If you have a perspective on how Natera can help with resources and education on this topic or if you’ve encountered a carrier screening case that raised unique counseling, reporting or workflow considerations, we’d love to hear about it. Share your perspective with Natera. 

References

1. Bajaj, K., & Gross, S. J. (2014). Carrier Screening: Past, Present, and Future. Journal of Clinical Medicine, 3(3), 1033–1042. https://doi.org/10.3390/jcm3031033
2. Committee Opinion No. 691: Carrier Screening for Genetic Conditions. (2017). Obstetrics and gynecology, 129(3), e41–e55. https://doi.org/10.1097/AOG.0000000000001952
3. Gregg, A. R., Aarabi, M., Klugman, S., Leach, N. T., Bashford, M. T., Goldwaser, T., Chen, E., Sparks, T. N., Reddi, H. V., Rajkovic, A., Dungan, J. S., & ACMG Professional Practice and Guidelines Committee (2021). Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genetics in medicine : official journal of the American College of Medical Genetics, 23(10), 1793–1806. https://doi.org/10.1038/s41436-021-01203-z
4. Sagaser, K. G., Malinowski, J., Westerfield, L., Proffitt, J., Hicks, M. A., Toler, T. L., Blakemore, K. J., Stevens, B. K., & Oakes, L. M. (2023). Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors. Journal of genetic counseling, 32(3), 540–557. https://doi.org/10.1002/jgc4.1676
5. Souter, V., Johnson, L., Becraft, E., Cantu-Weinstein, A., Tabriziani, H., Benn, P., & Kashtan, C. E. (2025). Carrier screening for Alport syndrome: The clinical importance of heterozygosity for pathogenic or likely pathogenetic variants. Journal of genetic counseling, 34(3), e70045. https://doi.org/10.1002/jgc4.70045
6. Souter, V., Becraft, E., Brummitt, S., Gall, B. J., Prigmore, B., Wang, Y., & Benn, P. (2024). Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States. Circulation. Genomic and precision medicine, 17(2), e004457. https://doi.org/10.1161/CIRCGEN.123.004457
7. Souter, V., Prigmore, B., Becraft, E., Repass, E., Smart, T., Sanapareddy, N., Schweitzer, M., Ortiz, J. B., Wang, Y., & Benn, P. (2023). Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy. Obstetrics and gynecology, 142(5), 1208–1216. https://doi.org/10.1097/AOG.0000000000005318

Lauren Tuttle, MS, LCGC (she/her)

Lauren Tuttle, MS, LCGC, earned her Master of Science in genetic counseling from the University of Arkansas for Medical Sciences in 2015. Before joining Natera, she worked as a general genetic counselor, supporting a diverse range of patients across multiple specialties and settings. As a laboratory genetic counselor at Natera, she supports the Horizon carrier screening and Fetal Focus products. She’s passionate about making genetic information accessible and meaningful, and she loves supporting patients and providers in regards to complex genetic information.