Implementation of fragile X syndrome carrier screening during prenatal diagnosis: A pilot study at a single center

Abstract

Background Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Prenatal screening of FXS allows for early identification and intervention. The present study explored the feasibility of FXS carrier screening during prenatal diagnosis for those who were not offered screening early in pregnancy or prior to conception. Methods Pregnant women to be offered amniotic fluid testing were recruited for the free voluntary carrier screening at a single center between August, 2017 and September, 2019. The number of CGG repeats in the 5’ un‐translated region of the fragile X mental retardation gene 1 (FMR1) was determined. Results 4286 of 7000 (61.2%) pregnant women volunteered for the screening. Forty (0.93%), five (0.11%), and three (0.07%) carriers for intermediate mutation (45–54 repeats), premutation (55–200 repeats) and full mutation (>200 repeats) of the FMR1 gene were identified respectively. None of the detected premutation alleles were inherited by the fetuses. Of the three full mutation carrier mothers, all had a family history and one transmitted a full mutation allele to her male fetus. Conclusion Implementation of FXS carrier screening during prenatal diagnosis may be considered for the need to increase screening for FXS.

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

“…Because the presence of a PM can lead to developmental disability in future generations, carrier screening has important reproductive and mental health implications for the woman who has to be tested, and it is relevant for early detection, intervention, and family planning. A recent study investigating the feasibility of fragile X carrier screening for pregnant women and for the fetuses during prenatal diagnosis reported that, over a total of 7000 pregnant women, approximately 61% of them consented to receive carrier screening [ 471 ]. The study identified five PM carriers and three women with a full mutation, and suggested that implementation of carrier screening during prenatal diagnosis may provide information about early intervention for those who have the FMR1 mutation, and information on the risk of having a child with FXS in the following pregnancies.…”

“…Importantly, the identification of women carriers of a PM who are at risk for FXPOI could lead to more effective reproductive interventions for those who want to have a child. In addition, it has been reported that prenatal screening is beneficial when considering the burden of raising a child with FXS [ 471 ].…”