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Medicine as it is understood today is an umbrella term that covers the detection, diagnosis, management, and prevention of disease. It is, rightly so, akin to a broad kitchen in which there can never be too many cooks. As physicians debate how best to treat genetic rare diseases (such as Duchenne muscular dystrophy, spinal muscular atrophy, and long chain fatty acid oxidation disorder, to name a few) in one corner, epidemiologists and public health experts are in another corner discussing ways to prevent the disease outbreak in the first place. 

This multidisciplinary approach to medicine, increasingly common in the 21st century, is the right way to go about tackling diseases from every angle possible. And with the global population currently over 7 billion and our world becoming more interconnected than ever, medicine must evolve to respond more quickly to emerging health threats to keep us all safe. Nothing demonstrates this as clearly as the current COVID-19 pandemic. 

Screening for a disease in at-risk groups is an effort by the medical community to diagnose certain conditions early, with the goal of improving patient outcomes. Screening is more common in diseases in which a defined group of people is at a much higher risk of developing it. Early detection means early treatment, which usually translates to improved quality of life.

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Carrier screening is the screening of conditions that have a high prevalence among defined racial/ethnic groups. Diseases that come to mind include sickle cell disease, which has a higher prevalence among the black population, and Tay-Sachs disease, which has a higher prevalence among the Ashkenazi Jewish population. 

Carrier screening is used to screen for individuals or couples who are at a higher risk of developing an autosomal recessive or an X-linked disorder. A study published in Genetics In Medicine sought to develop and answer a series of questions regarding the carrier screening process by developing a consensus group, with the goal of providing practical resources to the American College of Genetics and Genomics (ACMG). This consensus group consisted of authors of this study as well as the ACMG Professional Practice and Guidelines Committee. 

Carrier screening was first recommended for heritable autosomal recessive conditions about 50 years ago. The practice of carrier screening in medicine started in earnest with cystic fibrosis and spinal muscular atrophy. Next-generation sequencing is relatively inexpensive and incredibly useful in mapping out the sequence variants across many genes simultaneously. 

Thoughtful Questions and Important Answers

The consensus group developed a series of key questions surrounding carrier screening and sought to answer them through currently available research. Here is a list of the questions and short summaries of their answers:

1. Are analytical and clinical validity established for carrier screening?

Analytical validity of carrier screening is established by a lab according to Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) regulations and ACMG Laboratory Standards and Guidelines. Clinical validity is established according to the gene and condition, such as the association of the cystic fibrosis transmembrane conductance regulator (CFTR) gene with cystic fibrosis. It is important to note that a negative screening test does not eliminate the risk of being a carrier because the residual risk of being a carrier can never be zero.

2. Has clinical utility been established for carrier screening?

Carrier screening allows individuals and couples screened to make informed choices about their reproductive risks and options. In addition, carrier screening might pick up on secondary conditions, which can further strengthen informed decision-making. 

3. Is “expanded carrier screening” a precise term?

The word “expanded” is vague, and the consensus group proposes adopting a tiered approach to carrier screening, which will allow patients and physicians to communicate with greater precision.

4. What screening approach should be offered to patients considering carrier screening?

If we are to utilize a tiered screening model, the consensus group believes all pregnancies should be offered Tier 3 screening (Tier 3 is for conditions with a carrier frequency ≥1/200). Tier 4, which includes genes less common than Tier 3, should be considered when family history warrants it or if the pregnancy stems from a known or possible consanguineous relationship. Anything less than Tier 3 should not be routinely offered.

5. Which autosomal recessive conditions are appropriate for carrier screening?

All pregnant women should be offered Tier 3 screening for autosomal recessive and X-linked genes. In total, the consensus group recommended 97 autosomal recessive genes for Tier 3 screening. 

6. Which X-linked conditions are appropriate for carrier screening? 

The consensus group recommends carrier screening for X-linked conditions that carry a 1/40,000 disease prevalence. Sixteen genes have been identified, including for conditions such as Duchenne muscular dystrophy, hemophilia, and X-linked atrophic macular degeneration.

7. What should the clinician expect with regard to laboratory reporting of carrier screening results?

The consensus group believes that the testing approach and the detectable variant type should be clearly reported. Only pathogenic or likely pathogenic variants should be routinely reported to patients. Residual risk estimates should not be reported due to insufficient data. 

8. What should be emphasized during pretest and post-test counseling when performing carrier screening?

Patients should be made aware that carrier testing is optional and can be performed at any given time. Preconception screening should be recommended over prenatal screening to allow for more informed reproductive decision-making. In addition, carrier screening is not intended to replace newborn screening. 

Carrier Screening: A Window To Better Informed Decision-Making 

Carrier screening is best viewed as a tool to help people and couples wanting to have children make informed reproductive choices. It should never be coerced, and the full implications of this step should be explained to patients. It also cannot be used to test for all genetic conditions, as only a relative minority of genetic conditions are screened. 

Carrier screening represents a step forward in medicine because it allows patients to actively participate in decision-making. Although there are calls to make carrier screening universally available, the fact remains that access to carrier screening remains inequitable across income groups. The priority now should be to ensure that the most accurate and widely used carrier screening tests are available to as many people as possible, with the ultimate goal of improving carrier health outcomes.


Gregg AR, Aarabi M, Klugman S, et al. 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). Genet Med. Published online July 20, 2021. doi:10.1038/s41436-021-01203-z

Pletcher B, Gross S, Monaghan K, Driscoll DA, Watson MS. The future is now: carrier screening for all populations. Genet Med. 2008;10:33-36. doi:10.1097/GIM.0b013e31815f5934