In this issue of Genetics in Medicine, Hill et al. 1 conduct a systematic review of studies investigating population screening for fragile X syndrome (FXS) among two groups: women of reproductive age and newborns. Most of the studies obtained through their review focus on the psychosocial and counseling issues of screening adult women of reproductive age for the FMR1 mutation alleles, with one small pilot study examining newborn screening for FXS. Because of the unique biology of the FMR1 mutation, population screening for FXS raises concerns that are not found in population screening for disorders such as phenylketonuria and cystic fibrosis. For FMR1, two mutation classes are of medical concern: the premutation and the full mutation. Male premutation carriers pass on the premutation to all their daughters and are themselves at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) later in life. Female premutation carriers are at risk of having a child with FXS, of having fragile X-associated primary ovarian insufficiency (FXPOI) and of developing FXTAS; although the latter occurs at a much lower rate than in male carriers. Full mutation carrier males almost always have frank intellectual disabilities. The full mutation carried by women, however, is incompletely penetrant and variably expressed. This has led to a concern that identifying full mutation carrier females via population screening programs could lead to stigmatization of clinically unaffected females. For all these reasons, current guidelines recommend that population screening for FXS be limited to well-defined clinical research protocols. In their review, Hill et al. 1 find that screening adult women for FMR1 mutations is less controversial than newborn screening for FXS. Among adult women, preconception screening is preferred to screening during pregnancy. As Hill et al. 1 note, preconception screening would actually serve two purposes: assessment of a woman’s risk for having a child with FXS and assessment of her risk for FXPOI. Voluntary screening of adult women for FMR1 mutations to assess reproductive risk is generally viewed favorably by women, even among those who chose not to be screened. To date, there has been no evidence that offering voluntary screening to this population has any negative impact. As with any population screening for a genetic condition, family members would be identified as mutation carriers through cascade testing. Unique to FMR1 mutations, this also serves as predictive testing for the premutation lateonset disorders of FXPOI and FXTAS, in addition to the risk for offspring with FXS. This raises concerns of the impact on family members who did not consent to being screened. These concerns, however, are similar to those raised in testing for familial cancer predisposition syndromes, such as BRCA1 and BRCA2 testing. Unlike newborn screening, population screening of adult women of reproductive age would be done with their fully informed consent, thereby reducing the negative impact of screening. Access to education and expert genetic counseling services would be needed to help balance the risk to benefit ratio for each unique family. Turning to population screening for newborns brings up different concerns. The identification of FXS males in the newborn period would offer the opportunity for early educational intervention, prevent the “diagnostic odyssey” of trying to establish a diagnosis in an affected child, and inform couples about their risk of having another child with FXS. However, there are three major concerns regarding screening for FMR1 mutations during the newborn period. First, there is no diagnostic test to …