The women’s health business unit of Myriad Genetics Inc, Salt Lake City, has published the first data-driven evaluation of commonly stated recommendations of panel inclusion criteria for expanded carrier screening (ECS).1 The key findings of the evaluation are that current criteria can be ambiguous and should be clarified, and that broader use of ECS can identify more couples at increased risk of passing on serious inherited genetic conditions to their children.

An analysis of more than 55,000 patients tested with the Foresight 176-condition ECS panel identified how many carriers and at-risk couples would have been missed if the panel were constructed using different interpretations of existing criteria from health professional associations. For instance, one criterion states that screened conditions should have a carrier rate of at least 1 in 100, although it is not clear whether this threshold applies to X-linked conditions or whether it must be exceeded in any ethnicity or in all ethnicities.

The study also showed that such distinctions are clinically consequential. Depending on the definition used, a compliant panel may identify between 11% (3 conditions) and 89% (38 conditions) of couples that should be considered at-risk relative to the Foresight 176-condition panel. With the most restrictive interpretation—where the carrier rate threshold must be exceeded in all ethnicities—common conditions such as cystic fibrosis would be omitted from ECS. Clarifying current guidelines to include a 1 in 100 carrier rate for any ethnicity would result in a 38-condition panel that identifies 89% of at-risk couples.

The Foresight carrier screen is a genetic test that identifies couples who are at increased risk of passing on inherited conditions to their children. Foresight tests for more than 175 serious and clinically actionable conditions. It is estimated that serious genetic conditions affect 1 in 300 pregnancies.

“Existing professional opinions can be interpreted in many ways, which can create confusion and limit the identification of couples at risk for pregnancies affected with serious conditions,” notes James Goldberg, MD, a board-certified maternal-fetal medicine specialist, medical geneticist, and chief medical officer at Myriad Women’s Health. “Our study provides data that will be helpful to professional organizations as they update their guidelines to enable screening of many conditions in a clinically responsible manner, with the goal of maximizing the clinical utility of ECS for prospective parents.”

For further information, visit Myriad Genetics.

Reference

  1. Ben-Shachar R, Svenson A, Goldberg JD, Muzzey D. A data-driven evaluation of the size and content of expanded carrier screening panels. Genet Med. Published online, February 28, 2019; doi: 10.1038/s41436-019-0466-5.