ACMG Carrier Screening Updates: Overview and History

Progress in the medical field continues to make more information available to prospective parents, giving them more control to prepare and make health decisions. In the realm of genetic testing, we have seen advances in carrier screening provide a myriad of options for both parents and clinicians. Recently, the American College of Medical Genetics and Genomics (ACMG) released a practice resource for screening during pregnancy and preconception.

For the first time, ACMG categorized conditions for carrier screening into tiers. These tiers are based on several factors, including frequency, severity, and inclusion in prior guidelines. Based on the expert-led evaluation, ACMG released a list of 113 conditions for which all women should be offered testing. (Since testing for X-linked conditions is not recommended for men, the recommended panel for males includes 97 conditions.) Before this publication, only two conditions were recommended pan-ethnically by ACMG and ACOG (American College of Obstetricians and Gynecologists). Testing for conditions beyond the 113 is only to be considered based on pregnancy, patient, and family histories and is not to be offered routinely.

We’ve come a long way from when carrier screening started in the 1970s for conditions like Tay-Sachs disease in Ashkenazi Jewish individuals. Even in the 1990s, when genetic testing technologies improved, broad-scale molecular testing was only available for cystic fibrosis. Limited-size genotyping panels performed better in people with certain ethnic backgrounds. This is troublesome in a time when our population is more intermixed and self-reported ethnicity is often incorrect.

Since 2009, next generation sequencing (NGS) has been used in carrier screening and has allowed us to look for genetic changes associated with hundreds of diseases at a lower cost and in a fraction of the time. Further, testing can now detect a high percentage of disease-causing changes, regardless of an individual’s ethnic background. These factors opened the door to allow greater equity in testing. As ACMG notes, “Restricting carrier screening by using socially defined ethnic constructs or by self-identified ancestry is both inequitable and scientifically flawed.”

Despite the capabilities allowed by newer technology, there was still no guidance for how to use it. What conditions should everyone be tested for? As a genetic counselor speaking to many providers in different parts of the country, I have heard a lot of different opinions on the matter. And more commonly, I’ve heard confusion from providers looking for direction on what to offer. This ACMG publication is the first attempt at standardizing a list beyond cystic fibrosis and spinal muscular atrophy, and it’s a great first step forward.

With the huge increase in the number of genes for which patients should be offered testing, it was important to also have guidance on what exactly providers need to review with patients. To that end, ACMG included an outline of points providers should be comfortable discussing. This counseling helps all patients understand the testing and allows them to make informed decisions about pursuing it or not. It also helps ensure that a couple knows what types of results may come back and what options they have if they are at risk to have a child with a genetic condition. Ideally, testing is offered preconception, but it can still provide valuable information and options if done during a pregnancy.

Carrier testing still isn’t perfect; we can’t test for everything, and we can’t completely rule out risk for conditions even when a test is negative. But we can provide more information now than ever before. Beacon Carrier Screening at Fulgent Genetics has undergone a robust validation process and is built to be flexible. Our clear, concise reports highlight the most important findings that need to be reviewed in accordance with professional guidance. Fulgent’s adaptability has allowed us to offer a carrier screening panel as concordant as possible with ACMG’s recommendations while still providing other options for healthcare providers based on their own experiences and preferences and with each unique patient in mind.

This practice resource from ACMG is just the beginning. Our understanding of genetic disease will continue to evolve. Labs will need to innovate and adapt to keep up. Guidelines like this one provide a blueprint for labs to provide up-to-date services and for patients to undergo a continually improved, empowered, and equitable health care experience.

— Jamie Zdrodowski, MS, CGC