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

Mol Genet Genomic Med. 2019 Dec;7(12):e1024. doi: 10.1002/mgg3.1024. Epub 2019 Nov 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Decision Making
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / genetics*
  • Genetic Carrier Screening / methods*
  • Genetic Carrier Screening / statistics & numerical data
  • Humans
  • Practice Guidelines as Topic
  • Pregnancy
  • Young Adult

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein

Associated data

  • GENBANK/309550