Newborn, Carrier, and Early Childhood Screening Recommendations for Fragile X

Fragile X syndrome, diagnosed by Fragile X Mental Retardation 1 (FMR1) DNA testing, is the most common single-gene cause of inherited intellectual disability. The expanded CGG mutation in the FMR1 gene, once thought to have clinical significance limited to fragile X syndrome, is now well established as the cause for other fragile X-associated disorders including fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome in individuals with the premutation (carriers). The importance of early diagnostic and management issues, in conjunction with the identification of family members at risk for or affected by FMR1 mutations, has led to intense discussion about the appropriate timing for early identification of FMR1 mutations. This review includes an overview of the fragile X-associated disorders and screening efforts to date, and discussion of the advantages and barriers to FMR1 screening in newborns, during childhood, and in women of reproductive age. Comparison with screening programs for other common genetic conditions is discussed to arrive at action steps to increase the identification of families affected by FMR1 mutations. Pediatrics 2012;130:1126-1135