Fragile X syndrome carrier screening accompanied by genetic consultation has clinical utility in populations beyond those recommended by guidelines

Abstract

Abstract Background Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Many providers offer preconception or prenatal FXS carrier screening. However, guidelines recommend screening only for those with a family history or undergoing fertility evaluation. Wider screening has been resisted because of concerns about patient understanding of FXS‐associated inheritance patterns and phenotypes. Additionally, the clinical utility has been questioned. Methods We addressed these concerns by analyzing reproductive decision‐making and pregnancy management informed by post‐test genetic consultation among 122 FMR1 premutation carriers identified by expanded carrier screening. Results Sixty‐three percent of those screened met guidelines screening criteria; the remaining 37% did not. Ninety‐eight percent had undergone post‐test genetic consultation. Of respondents screened preconceptionally, 74% reported planning or pursuing actions to reduce the risk of an affected pregnancy; the extent to which couples planned/pursued these actions was not significantly different between those meeting either screening criterion (76%) versus those meeting neither criterion (55%). Of respondents screened prenatally, 41% pursued prenatal diagnostic testing; the extent to which couples pursued prenatal diagnosis was not significantly different between those who met either screening criterion (37%) versus those who met neither criterion (31%). Conclusion These results support the expansion of FXS screening criteria in guidelines.

Keywords

• carrier screening
• fragile X syndrome
• premutation