Newborn , Carrier , and Early Childhood Screening Recommendations for Fragile

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 AUTHORS: Liane Abrams, MS,a Amy Cronister, MS,b William T. Brown, MD, PhD,c Flora Tassone, PhD,d Stephanie L. Sherman, PhD,e Brenda Finucane, MS,f Allyn McConkieRosell, MS, PhD,g Randi Hagerman, MD,h Walter E. Kaufmann, MD,i,j Jonathan Picker, MD,k Sarah Coffey, MPH,l Debra Skinner, PhD,m Vanessa Johnson, PhD, RN-BC,n Robert Miller, BA,a and Elizabeth Berry-Kravis, MD, PhDo aNational Fragile X Foundation, Walnut Creek, California; bIntegrated Genetics, Westborough, Massachusetts; cDepartment of Human Genetics, New York State Office for People with Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island, New York; dDepartment of Biochemistry and Molecular Medicine, hFragile X Research, MIND Institute, and lDepartment of Neurologic Surgery, University California Davis Health System, University of California, Davis, Davis, California; eDepartment of Human Genetics, Emory University School of Medicine, Atlanta, Georgia; fGenetic Services Institute, Elwyn, Pennsylvania; gDepartment of Pediatrics, Duke University School of Medicine, Durham, North Carolina; iRett Syndrome Program, and kFragile X Program, Boston Children’s Hospital, Boston, Massachusetts; jDepartment of Neurology, Harvard Medical School, Boston, Massachusetts; mFrank Porter Graham Child Development Institute, Department of Anthropology, University North Carolina-Chapel Hill, Chapel Hill, North Carolina; nCollege of Nursing, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and oDepartment of Pediatrics, Neurologic Sciences, and Biochemistry, Rush University Medical Center, Chicago, Illinois