Background: Population screening for FMR1 mutations has been a topic of considerable discussion since the FMR1 gene was identified in 1991. Advances in understanding the molecular basis of fragile X syndrome (FXS) and in genetic testing methods have led to new, less expensive methodology to use for large screening endeavors. A core criterion for newborn screening is an accurate understanding of the public health burden of a disease, considering both disease severity and prevalence rate. This article addresses this need by reporting prevalence rates observed in a pilot newborn screening study for FXS in the US. Methods: Blood spot screening of 14,207 newborns (7,312 males and 6,895 females) was conducted in three birthing hospitals across the United States beginning in November 2008, using a PCR-based approach. Results: The prevalence of gray zone alleles was 1:66 females and 1:112 males, while the prevalence of a premutation was 1:209 females and 1:430 males. Differences in prevalence rates were observed among the various ethnic groups; specifically higher frequency for gray zone alleles in males was observed in the White group compared to the Hispanic and African-American groups. One full mutation male was identified (>200 CGG repeats). Conclusions: The presented pilot study shows that newborn screening in fragile X is technically feasible and provides overall prevalence of the premutation and gray zone alleles in the USA, suggesting that the prevalence of the premutation, particularly in males, is higher than has been previously reported.

OBJECTIVE: To determine recent trends in the diagnosis of children with fragile X syndrome (FXS) and identify factors associated with the timing of diagnosis.

The Early Childhood Outcomes (ECO) Center was funded by the Office of Special Education Programs to promote the development and implementation of child and family outcome measures for infants, toddlers, and preschoolers with disabilities. An evidence-based process with extensive stakeholder input led to the identification of five outcomes by which the effectiveness of services for families could be assessed: (a) families understand their child's strengths, abilities, and special needs; (b) families know their rights and advocate effectively for their child; (c) families help their child develop and learn; (d) families have support systems; and (e) families are able to gain access to desired services and activities in their community. These outcomes provide a framework by which states and the federal government could document whether early intervention and preschool programs are providing demonstrable benefits for families, and provide the basis for developing measurement systems to determine the extent to which such benefits have been attained.

Changes in the fragile X mental retardation 1 gene (FMR1) have been associated with specific phenotypes, most specifically those of fragile X syndrome (FXS), fragile X tremor/ataxia syndrome (FXTAS), and fragile X primary ovarian insufficiency (FXPOI). Evidence of increased risk for additional medical, psychiatric, and cognitive features and conditions is now known to exist for individuals with a premutation, although some features have been more thoroughly studied than others. This review highlights the literature on medical, reproductive, cognitive, and psychiatric features, primarily in females, that have been suggested to be associated with changes in the FMR1 gene. Based on this review, each feature is evaluated with regard to the strength of evidence of association with the premutation. Areas of need for additional focused research and possible intervention strategies are suggested.