A new approach to antenatal screening for Fragile X syndrome

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Abstract
Objectives: To describe a new approach to antenatal screening for Fragile X syndrome and to evaluate its effectiveness.Methods: We propose that Fragile X syndrome should be considered as a different disorder in males and in females. We also propose that only male Fragile X syndrome should be screened for, so the initial screening test would be the determination of fetal sex. This can now be performed from eight‐weeks gestation using a polymerase chain reaction (PCR) analysis on maternal serum. If this test reveals a male fetus, then the same blood sample can be used to determine the CGG repeat length in the DNA of the mother, again using the PCR technique and a Southern blot analysis where necessary. Mothers with positive results (>58 repeats) would be offered antenatal diagnosis (chorionic villus sampling or amniocentesis) to determine the CGG repeat length in cells from the fetus. The screening performance of this strategy was determined using the performance of the component tests.Results: The proposed strategy for screening for male Fragile X syndrome would have a 99% detection rate and a 0.1% false‐positive rate.Conclusion: After antenatal screening for Down syndrome, the proposed screening strategy would be the most effective method of preventing the birth of males with severe mental retardation. It would have a higher detection rate and a lower false‐positive rate than any other antenatal screening programme currently being undertaken, and there would be virtually no prenatal diagnosis of female Fragile X syndrome, which, because such a high proportion are phenotypically normal, has been a barrier to the introduction of screening. Copyright © 2003 John Wiley & Sons, Ltd.