Considering severity in the design of reproductive genetic carrier screening programs: screening for severe conditions.

Abstract

Reproductive genetic carrier screening (RGCS) provides information about people's chance of having children with certain genetic conditions, to inform reproductive decision making. RGCS at population scale requires a robust and streamlined program that is purposively designed and formally implemented to ensure equity and consistency. There are many considerations in selecting conditions, genes and variants for inclusion in RGCS, with severity of the genetic condition a key criterion. However, the concept of severity is complex and often underspecified in available guidelines. Severity is often determined in relation to other contextual features and can be experienced differently by individuals who all have the same condition. While some genetic conditions are unambiguously considered severe, there are many factors that contribute to how severe a condition is perceived to be (and by whom), and perspectives will vary. In this paper, we analyse why severity is an important criterion when selecting conditions, genes or variants to be included in RGCS. We suggest that screening programs should be oriented more towards variants and genes associated with severe conditions. We discuss the importance of taking a practical approach to gene selection in a carrier screening program when presenting the offer at population scale.