Fragile X Syndrome

Abstract

Despite earlier awareness of the need for pediatricians to recognize and diagnose developmental delay, the average age at diagnosis of fragile X syndrome (FXS) according to a study by Bailey et al,1 published in this issue of Pediatrics , has remained unchanged at 35 to 37 months of age. Although the survey (given between 2001 and 2007) suggests quicker referral to early childhood intervention (ECI) programs when abnormal development is suspected, the missing step responsible for the delay in the diagnosis of FXS seems to be that pediatricians do not consult a genetics specialist and/or order the test for FXS soon enough. This study reinforces that pediatricians must have a higher level of suspicion for FXS in certain patient populations with developmental delay, especially those with speech delay. FXS was first diagnosed showing fragility at the distal end of the X chromosome at the Xq27.3 locus. Better understanding of FXS and more accurate diagnosis was achieved when the gene for FXS was identified. The gene, fragile X mental retardation 1 ( FMR - 1 ), contains multiple repeats of 3 DNA bases (cytidine, guanine, and guanine [CGG], known as triplet repeats).2–5 There are 3 categories of CGG triplet repeats in the FMR - 1 gene. Up to 54 are considered normal, ∼59 to 200 triplet repeats of CGG are considered a premutation, and anything greater than 200 repeats is considered a full mutation. The FMR - 1 gene codes for the protein fragile X mental retardation protein (FMRP), which is found in … Address correspondence to Reuben Matalon, MD, PhD, University of Texas Medical Branch, Department of Pediatrics, Division of Genetics, 301 University Blvd, Galveston, TX 77555. E-mail: rmatalon{at}utmb.edu