{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:03:35Z","timestamp":1793189015768,"version":"4.5.0"},"reference-count":185,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:p>The FMR1 mutations can cause a variety of disabilities, including cognitive deficits, attention-deficit\/hyperactivity disorder, autism, and other socioemotional problems, in individuals with the full mutation form (fragile X syndrome) and distinct difficulties, including primary ovarian insufficiency, neuropathy and the fragile X-associated tremor\/ataxia syndrome, in some older premutation carriers. Therefore, multigenerational family involvement is commonly encountered when a proband is identified with a FMR1 mutation. Studies of metabotropic glutamate receptor 5 pathway antagonists in animal models of fragile X syndrome have demonstrated benefits in reducing seizures, improving behavior, and enhancing cognition. Trials of metabotropic glutamate receptor 5 antagonists are beginning with individuals with fragile X syndrome. Targeted treatments, medical and behavioral interventions, genetic counseling, and family supports are reviewed here.<\/jats:p>","DOI":"10.1542\/peds.2008-0317","type":"journal-article","created":{"date-parts":[[2008,12,29]],"date-time":"2008-12-29T15:58:03Z","timestamp":1230566283000},"page":"378-390","source":"Crossref","is-referenced-by-count":492,"title":["Advances in the Treatment of Fragile X Syndrome"],"prefix":"10.1542","volume":"123","author":[{"given":"Randi J.","family":"Hagerman","sequence":"first","affiliation":[{"name":"MIND. Institute"},{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Berry-Kravis","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Neurological Sciences"},{"name":"Biochemistry, Rush University Medical Center, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Center for Genetic Disorders of Cognition and Behavior, Kennedy-Krieger Institute, John Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Y.","family":"Ono","sequence":"additional","affiliation":[{"name":"MIND. Institute"},{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado at Denver Health Sciences Center, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ave","family":"Lachiewicz","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Kronk","sequence":"additional","affiliation":[{"name":"Department of Psychology in Education"},{"name":"School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Delahunty","sequence":"additional","affiliation":[{"name":"NeuroDevelopmental Center, Akron Children's Hospital, Akron, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hessl","sequence":"additional","affiliation":[{"name":"MIND. Institute"},{"name":"Psychiatry and Behavioral Sciences, University of California, Davis, School of Medicine, Sacramento, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannie","family":"Visootsak","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics"},{"name":"Pediatrics, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Picker","sequence":"additional","affiliation":[{"name":"Departments of Genetics"},{"name":"Child and Adolescent Psychiatry, Children's Hospital Boston, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Gane","sequence":"additional","affiliation":[{"name":"MIND. Institute"},{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tranfaglia","sequence":"additional","affiliation":[{"name":"FRAXA Research Foundation, Newburyport, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2009,1,1]]},"reference":[{"key":"2021120905122321800_R1","doi-asserted-by":"crossref","unstructured":"Loesch DZ, Huggins RM, Hagerman RJ. Phenotypic variation and FMRP levels in fragile X. Ment Retard Dev Disabil Res Rev.\u20082004;10(1):31\u201341","DOI":"10.1002\/mrdd.20006"},{"key":"2021120905122321800_R2","doi-asserted-by":"crossref","unstructured":"Tassone F, Hagerman RJ, Ikle\u0301 DN, et al. FMRP expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet.\u20081999;84(3):250\u2013261","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<250::AID-AJMG17>3.0.CO;2-4"},{"key":"2021120905122321800_R3","doi-asserted-by":"crossref","unstructured":"Pieretti M, Zhang FP, Fu YH, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell.\u20081991;66(4):817\u2013822","DOI":"10.1016\/0092-8674(91)90125-I"},{"key":"2021120905122321800_R4","doi-asserted-by":"crossref","unstructured":"De Boulle K, Verkerk AJ, Reyniers E, et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet.\u20081993;3(1):31\u201335","DOI":"10.1038\/ng0193-31"},{"key":"2021120905122321800_R5","doi-asserted-by":"crossref","unstructured":"Coffee B, Ikeda M, Budimirovic DB, Hjelm LN, Kaufmann WE, Warren ST. Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis. Am J Med Genet A.\u20082008;146A(10):1358\u20131367","DOI":"10.1002\/ajmg.a.32261"},{"key":"2021120905122321800_R6","doi-asserted-by":"crossref","unstructured":"Tassone F, Hagerman RJ, Taylor AK, et al. Clinical involvement and protein expression in individuals with the FMR1 premutation. Am J Med Genet.\u20082000;91(2):144\u2013152","DOI":"10.1002\/(SICI)1096-8628(20000313)91:2<144::AID-AJMG14>3.0.CO;2-V"},{"key":"2021120905122321800_R7","doi-asserted-by":"crossref","unstructured":"Crawford DC, Meadows KL, Newman JL, et al. Prevalence of the fragile X syndrome in African-Americans. Am J Med Genet.\u20082002;110(3):226\u2013233","DOI":"10.1002\/ajmg.10427"},{"key":"2021120905122321800_R8","unstructured":"Sherman S. Epidemiology. In: Hagerman RJ, Hagerman PJ, eds. Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. Baltimore, MD: Johns Hopkins University Press; 2002:136\u2013168"},{"key":"2021120905122321800_R9","doi-asserted-by":"crossref","unstructured":"Dawson AJ, Chodirker BN, Chudley AE. Frequency of FMR1 premutations in a consecutive newborn population by PCR screening of Guthrie blood spots. Biochem Mol Med.\u20081995;56(1):63\u201369","DOI":"10.1006\/bmme.1995.1057"},{"key":"2021120905122321800_R10","unstructured":"Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K. Prevalence of carriers of premutation-size alleles of the FMR1 gene and implications for the population genetics of the fragile X syndrome. Am J Hum Genet.\u20081995;57(5):1006\u20131018"},{"key":"2021120905122321800_R11","doi-asserted-by":"crossref","unstructured":"Dombrowski C, Levesque ML, Morel ML, Rouillard P, Morgan K, Rousseau F. Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet.\u20082002;11(4):371\u2013378","DOI":"10.1093\/hmg\/11.4.371"},{"key":"2021120905122321800_R12","doi-asserted-by":"crossref","unstructured":"Hagerman PJ. The fragile X prevalence paradox. J Med Genet.\u20082008;45(8):498\u2013499","DOI":"10.1136\/jmg.2008.059055"},{"key":"2021120905122321800_R13","doi-asserted-by":"crossref","unstructured":"Kenneson A, Zhang F, Hagedorn CH, Warren ST. Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum Mol Genet.\u20082001;10(14):1449\u20131454","DOI":"10.1093\/hmg\/10.14.1449"},{"key":"2021120905122321800_R14","doi-asserted-by":"crossref","unstructured":"Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet.\u20082000;66(1):6\u201315","DOI":"10.1086\/302720"},{"key":"2021120905122321800_R15","doi-asserted-by":"crossref","unstructured":"Kaufmann WE, Abrams MT, Chen W, Reiss AL. Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X syndrome. Am J Med Genet.\u20081999;83(4):286\u2013295","DOI":"10.1002\/(SICI)1096-8628(19990402)83:4<286::AID-AJMG10>3.0.CO;2-H"},{"key":"2021120905122321800_R16","doi-asserted-by":"crossref","unstructured":"Reiss AL, Dant CC. The behavioral neurogenetics of fragile X syndrome: analyzing gene-brain-behavior relationships in child developmental psychopathologies. Dev Psychopathol.\u20082003;15(4):927\u2013968","DOI":"10.1017\/S0954579403000464"},{"key":"2021120905122321800_R17","unstructured":"de Vries BB, Wiegers AM, Smits AP, et al. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet.\u20081996;58(5):1025\u20131032"},{"key":"2021120905122321800_R18","doi-asserted-by":"crossref","unstructured":"Aziz M, Stathopulu E, Callias M, et al. Clinical features of boys with fragile X premutations and intermediate alleles. Am J Med Genet B Neuropsychiatr Genet.\u20082003;121B(1):119\u2013127","DOI":"10.1002\/ajmg.b.20030"},{"key":"2021120905122321800_R19","doi-asserted-by":"crossref","unstructured":"Loesch DZ, Bui MQ, Grigsby J, et al. Effect of the fragile X status categories and the FMRP levels on executive functioning in fragile X males and females. Neuropsychology.\u20082003;17(4):646\u2013657","DOI":"10.1037\/0894-4105.17.4.646"},{"key":"2021120905122321800_R20","doi-asserted-by":"crossref","unstructured":"Moore CJ, Daly EM, Schmitz N, et al. A neuropsychological investigation of male premutation carriers of fragile X syndrome. Neuropsychologia.\u20082004;42(14):1934\u20131947","DOI":"10.1016\/j.neuropsychologia.2004.05.002"},{"key":"2021120905122321800_R21","doi-asserted-by":"crossref","unstructured":"Farzin F, Perry H, Hessl D, et al. Autism spectrum disorders and attention-deficit\/hyperactivity disorder in boys with the fragile X premutation. J Dev Behav Pediatr.\u20082006;27(2 suppl):S137\u2013S144","DOI":"10.1097\/00004703-200604002-00012"},{"key":"2021120905122321800_R22","doi-asserted-by":"crossref","unstructured":"Hessl D, Tassone F, Loesch DZ, et al. Abnormal elevation of FMR1 mRNA is associated with psychological symptoms in individuals with the fragile X premutation. Am J Med Genet B Neuropsychiatr Genet.\u20082005;139B(1):115\u2013121","DOI":"10.1002\/ajmg.b.30241"},{"key":"2021120905122321800_R23","doi-asserted-by":"crossref","unstructured":"Goodlin-Jones B, Tassone F, Gane LW, Hagerman RJ. Autistic spectrum disorder and the fragile X premutation. J Dev Behav Pediatr.\u20082004;25(6):392\u2013398","DOI":"10.1097\/00004703-200412000-00002"},{"key":"2021120905122321800_R24","doi-asserted-by":"crossref","unstructured":"Cornish KM, Kogan C, Turk J, et al. The emerging fragile X premutation phenotype: evidence from the domain of social cognition. Brain Cogn.\u20082005;57(1):53\u201360","DOI":"10.1016\/j.bandc.2004.08.020"},{"key":"2021120905122321800_R25","doi-asserted-by":"crossref","unstructured":"Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet.\u20082004;74(5):805\u2013816","DOI":"10.1086\/386296"},{"key":"2021120905122321800_R26","doi-asserted-by":"crossref","unstructured":"Allen EG, He W, Yadav-Shah M, Sherman SL. A study of the distributional characteristics of FMR1 transcript levels in 238 individuals. Hum Genet.\u20082004;114(5):439\u2013447","DOI":"10.1007\/s00439-004-1086-x"},{"key":"2021120905122321800_R27","doi-asserted-by":"crossref","unstructured":"Sullivan AK, Marcus M, Epstein MP, et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod.\u20082005;20(2):402\u2013412","DOI":"10.1093\/humrep\/deh635"},{"key":"2021120905122321800_R28","doi-asserted-by":"crossref","unstructured":"Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor\/ataxia syndrome in a premutation carrier population. JAMA.\u20082004;291(4):460\u2013469","DOI":"10.1001\/jama.291.4.460"},{"key":"2021120905122321800_R29","doi-asserted-by":"crossref","unstructured":"Coffey SM, Cook K, Tartaglia N, et al. Expanded clinical phenotype of women with the FMR1 premutation. Am J Med Genet A.\u20082008;146A(8):1009\u20131016","DOI":"10.1002\/ajmg.a.32060"},{"key":"2021120905122321800_R30","doi-asserted-by":"crossref","unstructured":"Jacquemont S, Hagerman RJ, Hagerman PJ, Leehey MA. Fragile-X syndrome and fragile X-associated tremor\/ataxia syndrome: two faces of FMR1. Lancet Neurol.\u20082007;6(1):45\u201355","DOI":"10.1016\/S1474-4422(06)70676-7"},{"key":"2021120905122321800_R31","doi-asserted-by":"crossref","unstructured":"Leehey MA, Berry-Kravis E, Min SJ, et al. Progression of tremor and ataxia in male carriers of the FMR1 premutation. Mov Disord.\u20082007;22(2):203\u2013206","DOI":"10.1002\/mds.21252"},{"key":"2021120905122321800_R32","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Coffey SM, Maselli R, et al. Neuropathy as a presenting feature in fragile X-associated tremor\/ataxia syndrome. Am J Med Genet A.\u20082007;143A(19):2256\u20132260","DOI":"10.1002\/ajmg.a.31920"},{"key":"2021120905122321800_R33","doi-asserted-by":"crossref","unstructured":"Willemsen R, Mientjes E, Oostra BA. FXTAS: a progressive neurologic syndrome associated with fragile X premutation. Curr Neurol Neurosci Rep.\u20082005;5(5):405\u2013410","DOI":"10.1007\/s11910-005-0065-5"},{"key":"2021120905122321800_R34","doi-asserted-by":"crossref","unstructured":"Hagerman RJ. Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. J Dev Behav Pediatr.\u20082006;27(1):63\u201374","DOI":"10.1097\/00004703-200602000-00012"},{"key":"2021120905122321800_R35","doi-asserted-by":"crossref","unstructured":"McConkie-Rosell A, Abrams L, Finucane B, et al. Recommendations from multi-disciplinary focus groups on cascade testing and genetic counseling for fragile X-associated disorders. J Genet Couns.\u20082007;16(5):593\u2013606","DOI":"10.1007\/s10897-007-9099-y"},{"key":"2021120905122321800_R36","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Hall DA, Coffey S, et al. Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin Interv Aging.\u20082008;3(2):251\u2013262","DOI":"10.2147\/CIA.S1794"},{"key":"2021120905122321800_R37","unstructured":"Hagerman RJ. Medical follow-up and pharmacotherapy. In: Hagerman RJ, Hagerman PJ, eds. Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. Baltimore, MD: Johns Hopkins University Press; 2002:287\u2013338"},{"key":"2021120905122321800_R38","doi-asserted-by":"crossref","unstructured":"Hatton DD, Buckley EG, Lachiewicz A, Roberts J. Ocular status of young boys with fragile X syndrome: a prospective study. J AAPOS.\u20081998;2(5):298\u2013302","DOI":"10.1016\/S1091-8531(98)90087-8"},{"key":"2021120905122321800_R39","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Altshul-Stark D, McBogg P. Recurrent otitis media in boys with the fragile X syndrome. Am J Dis Child.\u20081987;141(2):184\u2013187","DOI":"10.1001\/archpedi.1987.04460020074031"},{"key":"2021120905122321800_R40","doi-asserted-by":"crossref","unstructured":"Davids JR, Hagerman RJ, Eilert RE. Orthopaedic aspects of fragile-X syndrome. J Bone Joint Surg Am.\u20081990;72(6):889\u2013896","DOI":"10.2106\/00004623-199072060-00015"},{"key":"2021120905122321800_R41","unstructured":"Hagerman RJ. Physical and behavioral phenotype. In: Hagerman RJ, Hagerman PJ, eds. Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. Baltimore, MD: Johns Hopkins University Press; 2002:3\u2013109"},{"key":"2021120905122321800_R42","doi-asserted-by":"crossref","unstructured":"Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr.\u20082001;32(suppl 2):S1\u2013S31","DOI":"10.1097\/00005176-200100002-00001"},{"key":"2021120905122321800_R43","unstructured":"King RA, Hagerman RJ, Houghton M. Ocular findings in fragile X syndrome. Dev Brain Dysfunct.\u20081995;8:223\u2013229"},{"key":"2021120905122321800_R44","doi-asserted-by":"crossref","unstructured":"Wittenberger MD, Hagerman RJ, Sherman SL, et al. The FMR1 premutation and reproduction. Fertil Steril.\u20082007;87(3):456\u2013465","DOI":"10.1016\/j.fertnstert.2006.09.004"},{"key":"2021120905122321800_R45","doi-asserted-by":"crossref","unstructured":"Baumgardner TL, Reiss AL, Freund LS, Abrams MT. Specification of the neurobehavioral phenotype in males with fragile X syndrome. Pediatrics.\u20081995;95(5):744\u2013752","DOI":"10.1542\/peds.95.5.744"},{"key":"2021120905122321800_R46","doi-asserted-by":"crossref","unstructured":"Roberts JE, Boccia ML, Bailey DB, Hatton D, Skinner M. Cardiovascular indices of physiological arousal in boys with fragile X syndrome. Dev Psychobiol.\u20082001;39(2):107\u2013123","DOI":"10.1002\/dev.1035"},{"key":"2021120905122321800_R47","doi-asserted-by":"crossref","unstructured":"Hatton DD, Sideris J, Skinner M, et al. Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A.\u20082006;140A(17):1804\u20131813","DOI":"10.1002\/ajmg.a.31286"},{"key":"2021120905122321800_R48","doi-asserted-by":"crossref","unstructured":"Turk J. Fragile X syndrome and attentional deficits. J Appl Res Intellect Disabil.\u20081998;11:175\u2013191","DOI":"10.1111\/j.1468-3148.1998.tb00060.x"},{"key":"2021120905122321800_R49","doi-asserted-by":"crossref","unstructured":"Cornish KM, Turk J, Wilding J, et al. Annotation: deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approach. J Child Psychol Psychiatry.\u20082004;45(6):1042\u20131053","DOI":"10.1111\/j.1469-7610.2004.t01-1-00297.x"},{"key":"2021120905122321800_R50","doi-asserted-by":"crossref","unstructured":"Chiu S, Wegelin JA, Blank J, et al. Early acceleration of head circumference in children with fragile X syndrome and autism. J Dev Behav Pediatr.\u20082007;28(1):31\u201335","DOI":"10.1097\/01.DBP.0000257518.60083.2d"},{"key":"2021120905122321800_R51","doi-asserted-by":"crossref","unstructured":"Kau ASM, Tierney E, Bukelis I, et al. Social behavior profile in young males with fragile X syndrome: characteristics and specificity. Am J Med Genet A.\u20082004;126A(1):9\u201317","DOI":"10.1002\/ajmg.a.20218"},{"key":"2021120905122321800_R52","doi-asserted-by":"crossref","unstructured":"Miller LJ, McIntosh DN, McGrath J, et al. Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: a preliminary report. Am J Med Genet.\u20081999;83(4):268\u2013279","DOI":"10.1002\/(SICI)1096-8628(19990402)83:4<268::AID-AJMG7>3.0.CO;2-K"},{"key":"2021120905122321800_R53","unstructured":"Cohen IL, Fisch GS, Sudhalter V, et al. Social gaze, social avoidance, and repetitive behavior in fragile X males: a controlled study. Am J Ment Retard.\u20081988;92(5):436\u2013446"},{"key":"2021120905122321800_R54","doi-asserted-by":"crossref","unstructured":"Sullivan K, Hatton D, Hammer J, et al. ADHD symptoms in children with FXS. Am J Med Genet A.\u20082006;140(21):2275\u20132288","DOI":"10.1002\/ajmg.a.31388"},{"key":"2021120905122321800_R55","doi-asserted-by":"crossref","unstructured":"Lachiewicz AM, Dawson DV, Spiridigliozzi GA, McConkie-Rosell A. Arithmetic difficulties in females with the fragile X premutation. Am J Med Genet A.\u20082006;140(7):665\u2013672","DOI":"10.1002\/ajmg.a.31082"},{"key":"2021120905122321800_R56","doi-asserted-by":"crossref","unstructured":"Mazzocco MM, Singh Bhatia N, Lesniak-Karpiak K. Visuospatial skills and their association with math performance in girls with fragile X or Turner syndrome. Child Neuropsychol.\u20082006;12(2):87\u2013110","DOI":"10.1080\/09297040500266951"},{"key":"2021120905122321800_R57","doi-asserted-by":"crossref","unstructured":"Freund LS, Reiss AL, Abrams MT. Psychiatric disorders associated with fragile X in the young female. Pediatrics.\u20081993;91(2):321\u2013329","DOI":"10.1542\/peds.91.2.321"},{"key":"2021120905122321800_R58","doi-asserted-by":"crossref","unstructured":"Angkustsiri K, Wirojanan J, Deprey L, Gane LW, Hagerman RJ. Fragile X syndrome with anxiety disorder and exceptional verbal intelligence. Am J Med Genet A.\u20082008;146(3):376\u2013379","DOI":"10.1002\/ajmg.a.32118"},{"key":"2021120905122321800_R59","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr, Mesibov GB, Hatton DD, Clark RD, Roberts JE, Mayhew L. Autistic behavior in young boys with fragile X syndrome. J Autism Dev Disord.\u20081998;28(6):499\u2013508","DOI":"10.1023\/A:1026048027397"},{"key":"2021120905122321800_R60","doi-asserted-by":"crossref","unstructured":"Kaufmann WE, Cortell R, Kau AS, et al. Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet A.\u20082004;129A(3):225\u2013234","DOI":"10.1002\/ajmg.a.30229"},{"key":"2021120905122321800_R61","doi-asserted-by":"crossref","unstructured":"Rogers SJ, Wehner EA, Hagerman RJ. The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr.\u20082001;22(6):409\u2013417","DOI":"10.1097\/00004703-200112000-00008"},{"key":"2021120905122321800_R62","doi-asserted-by":"crossref","unstructured":"Clifford S, Dissanayake C, Bui QM, Huggins R, Taylor AK, Loesch DZ. Autism spectrum phenotype in males and females with fragile X full mutation and premutation. J Autism Dev Disord.\u20082007;37(4):738\u2013747","DOI":"10.1007\/s10803-006-0205-z"},{"key":"2021120905122321800_R63","doi-asserted-by":"crossref","unstructured":"Loesch DZ, Bui QM, Dissanayake C, et al. Molecular and cognitive predictors of the continuum of autistic behaviours in fragile X. Neurosci Biobehav Rev.\u20082007;31(3):315\u2013326","DOI":"10.1016\/j.neubiorev.2006.09.007"},{"key":"2021120905122321800_R64","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Rivera SM, Hagerman PJ. The fragile X family of disorders: a model for autism and targeted treatments. Curr Pediatr Rev.\u20082008;4(1):40\u201352","DOI":"10.2174\/157339608783565770"},{"key":"2021120905122321800_R65","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr, Hatton DD, Skinner M, Mesibov GB. Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. J Autism Dev Disord.\u20082001;31(2):165\u2013174","DOI":"10.1023\/A:1010747131386"},{"key":"2021120905122321800_R66","doi-asserted-by":"crossref","unstructured":"Hatton D, Hooper SR, Bailey DB, Skinner ML, Sullivan KM, Wheeler A. Problem behavior in boys with fragile X syndrome. Am J Med Genet.\u20082002;108(2):105\u2013116","DOI":"10.1002\/ajmg.10216"},{"key":"2021120905122321800_R67","doi-asserted-by":"crossref","unstructured":"Sabaratnam M, Murthy NV, Wijeratne A, Buckingham A, Payne S. Autistic-like behaviour profile and psychiatric morbidity in fragile X syndrome: a prospective ten-year follow-up study. Eur Child Adolesc Psychiatry.\u20082003;12(4):172\u2013177","DOI":"10.1007\/s00787-003-0333-3"},{"key":"2021120905122321800_R68","doi-asserted-by":"crossref","unstructured":"Roberts JE, Schaaf JM, Skinner M, et al. Academic skills of boys with fragile X syndrome: profiles and predictors. Am J Ment Retard.\u20082005;110(2):107\u2013120","DOI":"10.1352\/0895-8017(2005)110<107:ASOBWF>2.0.CO;2"},{"key":"2021120905122321800_R69","doi-asserted-by":"crossref","unstructured":"Backes M, Genc\u0327 B, Schreck J, Doerfler W, Lehmkuhl G, von Gontard A. Cognitive and behavioral profile of fragile X boys: correlations to molecular data. Am J Med Genet.\u20082000;95(2):150\u2013156","DOI":"10.1002\/1096-8628(20001113)95:2<150::AID-AJMG11>3.0.CO;2-1"},{"key":"2021120905122321800_R70","doi-asserted-by":"crossref","unstructured":"Borghgraef M, Fryns JP, Dielkens A, Pyck K, Van den Berghe H. Fragile X syndrome: a study of the psychological profile in 23 prepubertal patients. Clin Genet.\u20081987;32(3):179\u2013186","DOI":"10.1111\/j.1399-0004.1987.tb03351.x"},{"key":"2021120905122321800_R71","doi-asserted-by":"crossref","unstructured":"Munir F, Cornish KM, Wilding J. A neuropsychological profile of attention deficits in young males with fragile X syndrome. Neuropsychologia.\u20082000;38(9):1261\u20131270","DOI":"10.1016\/S0028-3932(00)00036-1"},{"key":"2021120905122321800_R72","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Murphy MA, Wittenberger MD. A controlled trial of stimulant medication in children with the fragile X syndrome. Am J Med Genet.\u20081988;30(1\u20132):377\u2013392","DOI":"10.1002\/ajmg.1320300138"},{"key":"2021120905122321800_R73","unstructured":"Amaria RN, Billeisen LL, Hagerman RJ. Medication use in fragile X syndrome. Ment Health Asp Dev Disabil.\u20082001;4(4):143\u2013147"},{"key":"2021120905122321800_R74","doi-asserted-by":"crossref","unstructured":"Berry-Kravis E, Potanos K. Psychopharmacology in fragile X syndrome: present and future. Ment Retard Dev Disabil Res Rev.\u20082004;10(1):42\u201348","DOI":"10.1002\/mrdd.20007"},{"key":"2021120905122321800_R75","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Miller LJ, McGrath-Clarke J, et al. Influence of stimulants on electrodermal studies in fragile X syndrome. Microsc Res Tech.\u20082002;57(3):168\u2013173","DOI":"10.1002\/jemt.10067"},{"key":"2021120905122321800_R76","unstructured":"Hagerman RJ, Riddle JE, Roberts LS, Brease K, Fulton M. A survey of the efficacy of clonidine in fragile X syndrome. Dev Brain Dysfunct.\u20081995;8(4\u20136):336\u2013344"},{"key":"2021120905122321800_R77","doi-asserted-by":"crossref","unstructured":"Ingrassia A, Turk J. The use of clonidine for severe and intractable sleep problems in children with neurodevelopmental disorders: a case series. Eur Child Adolesc Psychiatry.\u20082005;14(1):34\u201340","DOI":"10.1007\/s00787-005-0424-4"},{"key":"2021120905122321800_R78","doi-asserted-by":"crossref","unstructured":"Hunt RD, Arnsten AFT, Asbell MD. An open trial of guanfacine in treatment of attention deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry.\u20081995;34(1):50\u201354","DOI":"10.1097\/00004583-199501000-00013"},{"key":"2021120905122321800_R79","doi-asserted-by":"crossref","unstructured":"Horrigan J, Barnhill L. Guanfacine for treatment of attention-deficit hyperactivity disorder. J Child Adolesc Psychopharmacol.\u20081995;5(3):215\u2013223","DOI":"10.1089\/cap.1995.5.215"},{"key":"2021120905122321800_R80","doi-asserted-by":"crossref","unstructured":"Scahill L, Chappell PB, Kim YS, et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry.\u20082001;158(7):1067\u20131074","DOI":"10.1176\/appi.ajp.158.7.1067"},{"key":"2021120905122321800_R81","doi-asserted-by":"crossref","unstructured":"Newcorn JH, Schulz K, Harrison M, DeBellis MD, Udarbe JK, Halperin JM. \u03b12-Adrenergic agonists: neurochemistry, efficacy, and clinical guidelines for use in children. Pediatr Clin North Am.\u20081998;45(5):1099\u20131122","DOI":"10.1016\/S0031-3955(05)70064-X"},{"key":"2021120905122321800_R82","doi-asserted-by":"crossref","unstructured":"Torrioli MG, Vernacotola S, Peruzzi L, et al. A double-blind, parallel, multicenter comparison of l-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys. Am J Med Genet A.\u20082008;146(7):803\u2013812","DOI":"10.1002\/ajmg.a.32268"},{"key":"2021120905122321800_R83","doi-asserted-by":"crossref","unstructured":"Torrioli MG, Vernacotola S, Mariotti P, et al. Double-blind, placebo-controlled study of l-acetylcarnitine for the treatment of hyperactive behavior in fragile X syndrome [letter]. Am J Med Genet.\u20081999;87(4):366\u2013368","DOI":"10.1002\/(SICI)1096-8628(19991203)87:4<366::AID-AJMG18>3.0.CO;2-F"},{"key":"2021120905122321800_R84","unstructured":"Hagerman RJ, Fulton MJ, Leaman A, Riddle J, Hagerman K, Sobesky W. A survey of fluoxetine therapy in fragile X syndrome. Dev Brain Dysfunct.\u20081994;7:155\u2013164"},{"key":"2021120905122321800_R85","doi-asserted-by":"crossref","unstructured":"Hagerman RJ, Hills J, Scharfenaker S, Lewis H. Fragile X syndrome and selective mutism. Am J Med Genet.\u20081999;83(4):313\u2013317","DOI":"10.1002\/(SICI)1096-8628(19990402)83:4<313::AID-AJMG15>3.0.CO;2-F"},{"key":"2021120905122321800_R86","doi-asserted-by":"crossref","unstructured":"Henry CA, Steingard R, Venter J, Guptill J, Halpern EF, Bauman M. Treatment outcome and outcome associations in children with pervasive developmental disorders treated with selective serotonin reuptake inhibitors: a chart review. J Child Adolesc Psychopharmacol.\u20082006;16(1\u20132):187\u2013195","DOI":"10.1089\/cap.2006.16.187"},{"key":"2021120905122321800_R87","doi-asserted-by":"crossref","unstructured":"McDougle CJ, Kresch LE, Posey DJ. Repetitive thoughts and behavior in pervasive developmental disorders: treatment with serotonin reuptake inhibitors. J Autism Dev Disord.\u20082000;30(5):427\u2013435","DOI":"10.1023\/A:1005551523657"},{"key":"2021120905122321800_R88","doi-asserted-by":"crossref","unstructured":"King BH, Bostic JQ. An update on pharmacologic treatments for autism spectrum disorders. Child Adolesc Psychiatr Clin N Am.\u20082006;15(1):161\u2013175","DOI":"10.1016\/j.chc.2005.08.005"},{"key":"2021120905122321800_R89","doi-asserted-by":"crossref","unstructured":"Martin A, Koenig K, Anderson GM, Scahill L. Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: a prospective, open-label study. J Autism Dev Disord.\u20082003;33(1):77\u201385","DOI":"10.1023\/A:1022234605695"},{"key":"2021120905122321800_R90","doi-asserted-by":"crossref","unstructured":"Erickson CA, Posey DJ, Stigler KA, McDougle CJ. Pharmacologic treatment of autism and related disorders. Pediatr Ann.\u20082007;36(9):575\u2013585","DOI":"10.3928\/0090-4481-20070901-09"},{"key":"2021120905122321800_R91","doi-asserted-by":"crossref","unstructured":"DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. Dev Med Child Neurol.\u20082002;44(10):652\u2013659","DOI":"10.1111\/j.1469-8749.2002.tb00266.x"},{"key":"2021120905122321800_R92","doi-asserted-by":"crossref","unstructured":"Hollander E, Phillips A, Chaplin W, et al. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology.\u20082005;30(3):582\u2013589","DOI":"10.1038\/sj.npp.1300627"},{"key":"2021120905122321800_R93","doi-asserted-by":"crossref","unstructured":"Hammerness PG, Vivas FM, Geller DA. Selective serotonin reuptake inhibitors in pediatric psychopharmacology: a review of the evidence. J Pediatr.\u20082006;148(2):158\u2013165","DOI":"10.1016\/j.jpeds.2005.09.028"},{"key":"2021120905122321800_R94","doi-asserted-by":"crossref","unstructured":"Hessl D, Tassone F, Cordeiro L, et al. Brief report: aggression and stereotypic behavior in males with fragile X syndrome: moderating secondary genes in a \u201csingle gene\u201d disorder. J Autism Dev Disord.\u20082008;38(1):184\u2013189","DOI":"10.1007\/s10803-007-0365-5"},{"key":"2021120905122321800_R95","doi-asserted-by":"crossref","unstructured":"McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med.\u20082002;347(5):314\u2013321","DOI":"10.1056\/NEJMoa013171"},{"key":"2021120905122321800_R96","unstructured":"Berry-Kravis E, Sumis A. Clinic-based retrospective analysis of psychopharmacology for behavior in fragile X syndrome. Presented at the 10th International Fragile X Conference; July 19\u201323, 2006; Atlanta, GA"},{"key":"2021120905122321800_R97","doi-asserted-by":"crossref","unstructured":"Li M, Budin R, Fleming AS, Kapur S. Effects of novel antipsychotics, amisulpiride and aripiprazole, on maternal behavior in rats. Psychopharmacology (Berl).\u20082005;181(3):600\u2013610","DOI":"10.1007\/s00213-005-0091-7"},{"key":"2021120905122321800_R98","doi-asserted-by":"crossref","unstructured":"Fryns J, Haspeslagh M, Dereymaeker A, Volcke P, Van den Berghe H. A peculiar subphenotype in the fra(X) syndrome: extreme obesity-short stature-stubby hands and feet-diffuse hyperpigmentation: further evidence of disturbed hypothalamic function in the fra(X) syndrome?Clin Genet.\u20081987;32(6):388\u2013392","DOI":"10.1111\/j.1399-0004.1987.tb03155.x"},{"key":"2021120905122321800_R99","doi-asserted-by":"crossref","unstructured":"de Vries BB, Fryns JP, Butler MG, et al. Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype. J Med Genet.\u20081993;30(9):761\u2013766","DOI":"10.1136\/jmg.30.9.761"},{"key":"2021120905122321800_R100","doi-asserted-by":"crossref","unstructured":"Schrander-Stumpel C, Gerver W-T, Meyer H, Engelen J, Mulder H, Fryns J-P. Prader-Willi-like phenotype in fragile X syndrome. Clin Genet.\u20081994;45(4):175\u2013180","DOI":"10.1111\/j.1399-0004.1994.tb04018.x"},{"key":"2021120905122321800_R101","doi-asserted-by":"crossref","unstructured":"Nowicki ST, Tassone F, Ono MY, et al. The Prader-Willi phenotype of fragile X syndrome. J Dev Behav Pediatr.\u20082007;28(2):133\u2013138","DOI":"10.1097\/01.DBP.0000267563.18952.c9"},{"key":"2021120905122321800_R102","doi-asserted-by":"crossref","unstructured":"Chai JH, Locke DP, Greally JM, et al. Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi\/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet.\u20082003;73(4):898\u2013925","DOI":"10.1086\/378816"},{"key":"2021120905122321800_R103","doi-asserted-by":"crossref","unstructured":"Schenck A, Bardoni B, Langmann C, Harden N, Mandel JL, Giangrande A. CYFIP\/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein. Neuron.\u20082003;38(6):887\u2013898","DOI":"10.1016\/S0896-6273(03)00354-4"},{"key":"2021120905122321800_R104","doi-asserted-by":"crossref","unstructured":"Nishimura Y, Martin CL, Vazquez-Lopez A, et al. Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Hum Mol Genet.\u20082007;16(14):1682\u20131698","DOI":"10.1093\/hmg\/ddm116"},{"key":"2021120905122321800_R105","doi-asserted-by":"crossref","unstructured":"Chen C, Visootsak J, Dills S, Graham JM Jr. Prader-Willi syndrome: an update and review for the primary pediatrician. Clin Pediatr (Phila).\u20082007;46(7):580\u2013591","DOI":"10.1177\/0009922807299314"},{"key":"2021120905122321800_R106","unstructured":"Forster J, Gourash L. Food Security. Pittsburgh, PA: Pittsburgh Partnership; 2005"},{"key":"2021120905122321800_R107","unstructured":"Balko K. Red, Yellow, Green System for Weight Management. Sarasota, FL: Prader-Willi Syndrome Association; 2005"},{"key":"2021120905122321800_R108","unstructured":"Ribacoba Montero R, Salas Puig J, Ferna\u0301ndez Toral J, Ferna\u0301ndez Marti\u0301nez JM, Moral Rato M. Fragile X syndrome and epilepsy [in Spanish]. Neurologia.\u20081995;10(2):70\u201375"},{"key":"2021120905122321800_R109","doi-asserted-by":"crossref","unstructured":"Sabaratnam M, Vroegop PG, Gangadharan SK. Epilepsy and EEG findings in 18 males with fragile X syndrome. Seizure.\u20082001;10(1):60\u201363","DOI":"10.1053\/seiz.2000.0492"},{"key":"2021120905122321800_R110","doi-asserted-by":"crossref","unstructured":"Musumeci SA, Hagerman RJ, Ferri R, et al. Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia.\u20081999;40(8):1092\u20131099","DOI":"10.1111\/j.1528-1157.1999.tb00824.x"},{"key":"2021120905122321800_R111","doi-asserted-by":"crossref","unstructured":"Berry-Kravis E. Epilepsy in fragile X syndrome. Dev Med Child Neurol.\u20082002;44(11):724\u2013728","DOI":"10.1111\/j.1469-8749.2002.tb00277.x"},{"key":"2021120905122321800_R112","doi-asserted-by":"crossref","unstructured":"Incorpora G, Sorge G, Sorge A, Pavone L. Epilepsy in fragile X syndrome. Brain Dev.\u20082002;24(8):766\u2013769","DOI":"10.1016\/S0387-7604(02)00102-X"},{"key":"2021120905122321800_R113","doi-asserted-by":"crossref","unstructured":"Musumeci SA, Ferri R, Elia M, Colognola RM, Bergonzi P, Tassinari CA. Epilepsy and fragile X syndrome: a follow-up study. Am J Med Genet.\u20081991;38(2\u20133):511\u2013513","DOI":"10.1002\/ajmg.1320380276"},{"key":"2021120905122321800_R114","doi-asserted-by":"crossref","unstructured":"Rees M, Diebold U, Parker K, Doose H, Gardiner RM, Whitehouse WP. Benign childhood epilepsy with centrotemporal spikes and the focal sharp wave trait is not linked to the fragile X region. Neuropediatrics.\u20081993;24(4):211\u2013213","DOI":"10.1055\/s-2008-1071542"},{"key":"2021120905122321800_R115","doi-asserted-by":"crossref","unstructured":"Garci\u0301a-Nonell C, Ratera ER, Harris SW, et al. Secondary medical diagnosis in fragile X syndrome with and without autism spectrum disorder. Am J Med Genet A.\u20082008;146A(15):1911\u20131916","DOI":"10.1002\/ajmg.a.32290"},{"key":"2021120905122321800_R116","doi-asserted-by":"crossref","unstructured":"D'Hulst C, Kooy RF. The GABAA receptor: a novel target for treatment of fragile X?Trends Neurosci.\u20082007;30(8):425\u2013431","DOI":"10.1016\/j.tins.2007.06.003"},{"key":"2021120905122321800_R117","unstructured":"Rogawski MA, Reddy DS. Neurosteroids: endogenous modulators of seizure susceptibility. In: Rho JM, Sankar R, Cavazos J, eds. Epilepsy: Scientific Foundations of Clinical Practice. New York, NY: Marcel Dekker; 2004:319\u2013355"},{"key":"2021120905122321800_R118","doi-asserted-by":"crossref","unstructured":"Addae JI, Ali N, Youssef FF, Stone TW. AMPA receptor activation reduces epileptiform activity in the rat neocortex. Brain Res.\u20082007;1158:151\u2013157","DOI":"10.1016\/j.brainres.2007.05.002"},{"key":"2021120905122321800_R119","doi-asserted-by":"crossref","unstructured":"Bagni C, Greenough WT. From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat Rev Neurosci.\u20082005;6(5):376\u2013387","DOI":"10.1038\/nrn1667"},{"key":"2021120905122321800_R120","doi-asserted-by":"crossref","unstructured":"Grossman AW, Aldridge GM, Weiler IJ, Greenough WT. Local protein synthesis and spine morphogenesis: fragile X syndrome and beyond. J Neurosci.\u20082006;26(27):7151\u20137155","DOI":"10.1523\/JNEUROSCI.1790-06.2006"},{"key":"2021120905122321800_R121","doi-asserted-by":"crossref","unstructured":"Weiler IJ, Spangler CC, Klintsova AY, et al. Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. Proc Natl Acad Sci U S A.\u20082004;101(50):17504\u201317509","DOI":"10.1073\/pnas.0407533101"},{"key":"2021120905122321800_R122","doi-asserted-by":"crossref","unstructured":"Aschrafi A, Cunningham BA, Edelman GM, Vanderklish PW. The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Proc Natl Acad Sci U S A.\u20082005;102(6):2180\u20132185","DOI":"10.1073\/pnas.0409803102"},{"key":"2021120905122321800_R123","doi-asserted-by":"crossref","unstructured":"Huber KM, Gallagher SM, Warren ST, Bear MF. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A.\u20082002;99(11):7746\u20137750","DOI":"10.1073\/pnas.122205699"},{"key":"2021120905122321800_R124","doi-asserted-by":"crossref","unstructured":"Koekkoek SK, Yamaguchi K, Milojkovic BA, et al. Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in fragile X syndrome. Neuron.\u20082005;47(3):339\u2013352","DOI":"10.1016\/j.neuron.2005.07.005"},{"key":"2021120905122321800_R125","doi-asserted-by":"crossref","unstructured":"Nosyreva ED, Huber KM. Metabotropic receptor-dependent long-term depression persists in the absence of protein synthesis in the mouse model of fragile X syndrome. J Neurophysiol.\u20082006;95(5):3291\u20133295","DOI":"10.1152\/jn.01316.2005"},{"key":"2021120905122321800_R126","doi-asserted-by":"crossref","unstructured":"Li J, Pelletier MR, Perez Velazquez JL, Carlen PL. Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol Cell Neurosci.\u20082002;19(2):138\u2013151","DOI":"10.1006\/mcne.2001.1085"},{"key":"2021120905122321800_R127","doi-asserted-by":"crossref","unstructured":"Lauterborn JC, Rex CS, Kramar E, et al. Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome. J Neurosci.\u20082007;27(40):10685\u201310694","DOI":"10.1523\/JNEUROSCI.2624-07.2007"},{"key":"2021120905122321800_R128","doi-asserted-by":"crossref","unstructured":"Nakamoto M, Nalavadi V, Epstein MP, Narayanan U, Bassell GJ, Warren ST. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci U S A.\u20082007;104(39):15537\u201315542","DOI":"10.1073\/pnas.0707484104"},{"key":"2021120905122321800_R129","doi-asserted-by":"crossref","unstructured":"Irwin SA, Idupulapati M, Gilbert ME, et al. Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet.\u20082002;111(2):140\u2013146","DOI":"10.1002\/ajmg.10500"},{"key":"2021120905122321800_R130","doi-asserted-by":"crossref","unstructured":"Chuang SC, Zhao W, Bauchwitz R, Yan Q, Bianchi R, Wong RK. Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model. J Neurosci.\u20082005;25(35):8048\u20138055","DOI":"10.1523\/JNEUROSCI.1777-05.2005"},{"key":"2021120905122321800_R131","doi-asserted-by":"crossref","unstructured":"Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci.\u20082004;27(7):370\u2013377","DOI":"10.1016\/j.tins.2004.04.009"},{"key":"2021120905122321800_R132","doi-asserted-by":"crossref","unstructured":"Bear MF. Therapeutic implications of the mGluR theory of fragile X mental retardation. Genes Brain Behav.\u20082005;4(6):393\u2013398","DOI":"10.1111\/j.1601-183X.2005.00135.x"},{"key":"2021120905122321800_R133","doi-asserted-by":"crossref","unstructured":"Do\u0308len G, Osterweil E, Rao BS, et al. Correction of fragile X syndrome in mice. Neuron.\u20082007;56(6):955\u2013962","DOI":"10.1016\/j.neuron.2007.12.001"},{"key":"2021120905122321800_R134","doi-asserted-by":"crossref","unstructured":"Gasparini F, Lingenhohl K, Stoehr N, et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology.\u20081999;38(10):1493\u20131503","DOI":"10.1016\/S0028-3908(99)00082-9"},{"key":"2021120905122321800_R135","doi-asserted-by":"crossref","unstructured":"Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP. Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology.\u20082005;49(7):1053\u20131066","DOI":"10.1016\/j.neuropharm.2005.06.004"},{"key":"2021120905122321800_R136","doi-asserted-by":"crossref","unstructured":"McBride SM, Choi CH, Wang Y, et al. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron.\u20082005;45(5):753\u2013764","DOI":"10.1016\/j.neuron.2005.01.038"},{"key":"2021120905122321800_R137","doi-asserted-by":"crossref","unstructured":"Tucker B, Richards RI, Lardelli M. Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome. Hum Mol Genet.\u20082006;15(23):3446\u20133458","DOI":"10.1093\/hmg\/ddl422"},{"key":"2021120905122321800_R138","doi-asserted-by":"crossref","unstructured":"Slassi A, Isaac M, Edwards L, et al. Recent advances in non-competitive mGlu5 receptor antagonists and their potential therapeutic applications. Curr Top Med Chem.\u20082005;5(9):897\u2013911","DOI":"10.2174\/1568026054750236"},{"key":"2021120905122321800_R139","doi-asserted-by":"crossref","unstructured":"Porter RH, Jaeschke G, Spooren W, et al. Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J Pharmacol Exp Ther.\u20082005;315(2):711\u2013721","DOI":"10.1124\/jpet.105.089839"},{"key":"2021120905122321800_R140","unstructured":"Itil T, Seaman P, Huque M, et al. The clinical and quantitative EEG effects and plasma levels of fenbam (McN-3377) in subjects with anxiety: an open rising dose tolerance and efficacy study. Curr Ther Res.\u20081978;24(6):708\u2013724"},{"key":"2021120905122321800_R141","doi-asserted-by":"crossref","unstructured":"Pecknold JC, McClure DJ, Appeltauer L, Wrzesinski L, Allan T. Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebo-controlled study. J Clin Psychopharmacol.\u20081982;2(2):129\u2013133","DOI":"10.1097\/00004714-198204000-00010"},{"key":"2021120905122321800_R142","unstructured":"Friedmann C, Davis L, Ciccone P, Rubin R. Phase II double-blind controlled study of a new anxiolytic, fenobam (McN-3377) vs placebo. Curr Ther Res.\u20081980;27(2):144\u2013151"},{"key":"2021120905122321800_R143","unstructured":"LaPierre Y, Oyewumi L. Fenobam: another anxiolytic?Curr Ther Res.\u20081982;31(1):95\u2013101"},{"key":"2021120905122321800_R144","doi-asserted-by":"crossref","unstructured":"Spooren WP, Vassout A, Neijt HC, et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther.\u20082000;295(3):1267\u20131275","DOI":"10.1016\/S0022-3565(24)39029-9"},{"key":"2021120905122321800_R145","doi-asserted-by":"crossref","unstructured":"Tatarczyn\u0303ska E, Klodzin\u0303ska A, Chojnacka-Wo\u0301jcik E, et al. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol.\u20082001;132(7):1423\u20131430","DOI":"10.1038\/sj.bjp.0703923"},{"key":"2021120905122321800_R146","doi-asserted-by":"crossref","unstructured":"Berridge MJ. The Albert Lasker Medical Awards: inositol trisphosphate, calcium, lithium, and cell signaling. JAMA.\u20081989;262(13):1834\u20131841","DOI":"10.1001\/jama.262.13.1834"},{"key":"2021120905122321800_R147","doi-asserted-by":"crossref","unstructured":"Takei K, Shin RM, Inoue T, Kato K, Mikoshiba K. Regulation of nerve growth mediated by inositol 1,4,5-trisphosphate receptors in growth cones. Science.\u20081998;282(5394):1705\u20131708","DOI":"10.1126\/science.282.5394.1705"},{"key":"2021120905122321800_R148","doi-asserted-by":"crossref","unstructured":"Larsen GA, Berg-Johnsen J, Moe MC, Vinje ML. Calcium-dependent protein kinase C activation in acutely isolated neurons during oxygen and glucose deprivation. Neurochem Res.\u20082004;29(10):1931\u20131937","DOI":"10.1023\/B:NERE.0000042220.16373.29"},{"key":"2021120905122321800_R149","unstructured":"Bauchwitz R. GSK3 inhibitors and mGluR5 antagonists can produce an additive rescue of fragile X mouse phenotypes. Presented at the 10th International Fragile X Conference; July 19\u201323, 2006; Atlanta, GA"},{"key":"2021120905122321800_R150","doi-asserted-by":"crossref","unstructured":"Berry-Kravis E, Sumis A, Hervey C, et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr.\u20082008;29(4):293\u2013302","DOI":"10.1097\/DBP.0b013e31817dc447"},{"key":"2021120905122321800_R151","doi-asserted-by":"crossref","unstructured":"Berry-Kravis E, Krause SE, Block SS, et al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol.\u20082006;16(5):525\u2013540","DOI":"10.1089\/cap.2006.16.525"},{"key":"2021120905122321800_R152","doi-asserted-by":"crossref","unstructured":"Lauterborn JC, Lynch G, Vanderklish P, Arai A, Gall CM. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci.\u20082000;20(1):8\u201321","DOI":"10.1523\/JNEUROSCI.20-01-00008.2000"},{"key":"2021120905122321800_R153","doi-asserted-by":"crossref","unstructured":"Reiss AL, Hall SS. Fragile X syndrome: assessment and treatment implications. Child Adolesc Psychiatr Clin N Am.\u20082007;16(3):663\u2013675","DOI":"10.1016\/j.chc.2007.03.001"},{"key":"2021120905122321800_R154","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr, Skinner D, Hatton D, Roberts J. Family experiences and factors associated with the diagnosis of fragile X syndrome. J Dev Behav Pediatr.\u20082000;21(5):315\u2013321","DOI":"10.1097\/00004703-200010000-00001"},{"key":"2021120905122321800_R155","doi-asserted-by":"crossref","unstructured":"Restivo L, Ferrari F, Passino E, et al. Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proc Natl Acad Sci U S A.\u20082005;102(32):11557\u201311562","DOI":"10.1073\/pnas.0504984102"},{"key":"2021120905122321800_R156","doi-asserted-by":"crossref","unstructured":"Glaser B, Hessl D, Dyer-Friedman J, et al. Biological and environmental contributions to adaptive behavior in fragile X syndrome. Am J Med Genet A.\u20082003;117A(1):21\u201329","DOI":"10.1002\/ajmg.a.10549"},{"key":"2021120905122321800_R157","doi-asserted-by":"crossref","unstructured":"Dyer-Friedman J, Glaser B, Hessl D, et al. Genetic and environmental influences on the cognitive outcomes of children with fragile X syndrome. J Am Acad Child Adolesc Psychiatry.\u20082002;41(3):237\u2013244","DOI":"10.1097\/00004583-200203000-00002"},{"key":"2021120905122321800_R158","doi-asserted-by":"crossref","unstructured":"Hessl D, Dyer-Friedman J, Glaser B, et al. The influence of environmental and genetic factors on behavior problems and autistic symptoms in boys and girls with fragile X syndrome. Pediatrics.\u20082001;108(5). Available at: www.pediatrics.org\/cgi\/content\/full\/108\/5\/e88","DOI":"10.1542\/peds.108.5.e88"},{"key":"2021120905122321800_R159","doi-asserted-by":"crossref","unstructured":"Hessl D, Glaser B, Dyer-Friedman J, Reiss AL. Social behavior and cortisol reactivity in children with fragile X syndrome. J Child Psychol Psychiatry.\u20082006;47(6):602\u2013610","DOI":"10.1111\/j.1469-7610.2005.01556.x"},{"key":"2021120905122321800_R160","doi-asserted-by":"crossref","unstructured":"Hessl D, Glaser B, Dyer-Friedman J, et al. Cortisol and behavior in fragile X syndrome. Psychoneuroendocrinology.\u20082002;27(7):855\u2013872","DOI":"10.1016\/S0306-4530(01)00087-7"},{"key":"2021120905122321800_R161","doi-asserted-by":"crossref","unstructured":"Weiskop S, Richdale A, Matthews J. Behavioural treatment to reduce sleep problems in children with autism or fragile X syndrome. Dev Med Child Neurol.\u20082005;47(2):94\u2013104","DOI":"10.1017\/S0012162205000186"},{"key":"2021120905122321800_R162","unstructured":"Hills-Epstein J, Riley K, Sobesky W. The treatment of emotional and behavioral problems. In: Hagerman RJ, Hagerman PJ, eds. Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. Baltimore, MD: Johns Hopkins University Press; 2002:339\u2013362"},{"key":"2021120905122321800_R163","doi-asserted-by":"crossref","unstructured":"Lord C, Wagner A, Rogers S, et al. Challenges in evaluating psychosocial interventions for autistic spectrum disorders. J Autism Dev Disord.\u20082005;35(6):695\u2013708","DOI":"10.1007\/s10803-005-0017-6"},{"key":"2021120905122321800_R164","doi-asserted-by":"crossref","unstructured":"Schopler E, Mesibov G, Shigley R, Bashford A. Helping autistic children through their parents: the TEACCH model. In: Reynolds CR, Gutkin TR, eds. The Handbook of School Psychology. New York, NY: Wiley; 1984:629\u2013643","DOI":"10.1007\/978-1-4899-2293-9_4"},{"key":"2021120905122321800_R165","unstructured":"Rogers SJ, Hall T, Osaki D, Reaven J, Herbison J. The Denver model: a comprehensive, integrated educational approach to young children with autism and their families. In: Handelman JS, Harris SL, eds. Preschool Education Programs for Children With Autism. 2nd ed. Austin, TX: Pro-ed; 2001:95\u2013134"},{"key":"2021120905122321800_R166","doi-asserted-by":"crossref","unstructured":"Koegel RL, Koegel LK, McNerney EK. Pivotal areas in intervention for autism. J Clin Child Psychol.\u20082001;30(1):19\u201332","DOI":"10.1207\/S15374424JCCP3001_4"},{"key":"2021120905122321800_R167","doi-asserted-by":"crossref","unstructured":"Smith T, Mozingo D, Mruzek DW, Zarcone JR. Applied behavior analysis in the treatment of autism. In: Hollander E, Anagnostou E, eds. Clinical Manual for the Treatment of Autism. Washington, DC: American Psychiatric Publishing; 2007:153\u2013177","DOI":"10.1176\/appi.books.9781615377633.lg08"},{"key":"2021120905122321800_R168","unstructured":"Braden ML. Education. In: Weber J, ed. Children With Fragile X Syndrome: A Parent's Guide. Bethesda, MD: Woodbine House; 2000:243\u2013305"},{"key":"2021120905122321800_R169","doi-asserted-by":"crossref","unstructured":"McConkie-Rosell A, Finucane BM, Cronister AC, Abrams L, Bennett RL, Pettersen BJ. Genetic counseling for fragile X syndrome: updated recommendations of the National Society of Genetic Counselors. J Genet Couns.\u20082005;14(4):249\u2013270","DOI":"10.1007\/s10897-005-4802-x"},{"key":"2021120905122321800_R170","doi-asserted-by":"crossref","unstructured":"Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med.\u20082005;7(8):584\u2013587","DOI":"10.1097\/01.GIM.0000182468.22666.dd"},{"key":"2021120905122321800_R171","doi-asserted-by":"crossref","unstructured":"McConkie-Rosell A, Robinson H, Wake S, Staley LW, Heller K, Cronister A. Dissemination of genetic risk information to relatives in the fragile X syndrome: guidelines for genetic counselors. Am J Med Genet.\u20081995;59(4):426\u2013430","DOI":"10.1002\/ajmg.1320590406"},{"key":"2021120905122321800_R172","unstructured":"Gane L, Cronister A. Genetic counseling. In: Hagerman RJ, Hagerman PJ, eds. The Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. Baltimore, MD: Johns Hopkins University Press; 2002:251\u2013286"},{"key":"2021120905122321800_R173","doi-asserted-by":"crossref","unstructured":"Cederbaum S. Newborn screening: the spigot is open and threatens to become a flood. J Pediatr.\u20082007;151(2):108\u2013110","DOI":"10.1016\/j.jpeds.2007.04.035"},{"key":"2021120905122321800_R174","doi-asserted-by":"crossref","unstructured":"Berry-Kravis E, Abrams L, Coffey SM, et al. Fragile X-associated tremor\/ataxia syndrome: clinical features, genetics, and testing guidelines. Mov Disord.\u20082007;22(14):2018\u20132030","DOI":"10.1002\/mds.21493"},{"key":"2021120905122321800_R175","doi-asserted-by":"crossref","unstructured":"Musci TJ, Caughey AB. Cost-effectiveness analysis of prenatal population-based fragile X carrier screening. Am J Obstet Gynecol.\u20082005;192(6):1905\u20131912","DOI":"10.1016\/j.ajog.2005.02.052"},{"key":"2021120905122321800_R176","doi-asserted-by":"crossref","unstructured":"Cronister A, DiMaio M, Mahoney MJ, Donnenfeld AE, Hallam S. Fragile X syndrome carrier screening in the prenatal genetic counseling setting. Genet Med.\u20082005;7(4):246\u2013250","DOI":"10.1097\/01.GIM.0000159898.90221.D3"},{"key":"2021120905122321800_R177","doi-asserted-by":"crossref","unstructured":"Pesso R, Berkenstadt M, Cuckle H, et al. Screening for fragile X syndrome in women of reproductive age. Prenat Diagn.\u20082000;20(8):611\u2013614","DOI":"10.1002\/1097-0223(200008)20:8<611::AID-PD881>3.0.CO;2-M"},{"key":"2021120905122321800_R178","doi-asserted-by":"crossref","unstructured":"Jacquemont S, Leehey MA, Hagerman RJ, Beckett LA, Hagerman PJ. Size bias of fragile X premutation alleles in late-onset movement disorders. J Med Genet.\u20082006;43(10):804\u2013809","DOI":"10.1136\/jmg.2006.042374"},{"key":"2021120905122321800_R179","doi-asserted-by":"crossref","unstructured":"Hall DA, Hagerman RJ, Hagerman PJ, Jacquemont S, Leehey MA. Prevalence of FMR1 repeat expansions in movement disorders: a systematic review. Neuroepidemiology.\u20082006;26(3):151\u2013155","DOI":"10.1159\/000091656"},{"key":"2021120905122321800_R180","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr, Beskow LM, Davis AM, Skinner D. Changing perspectives on the benefits of newborn screening. Ment Retard Dev Disabil Res Rev.\u20082006;12(4):270\u2013279","DOI":"10.1002\/mrdd.20119"},{"key":"2021120905122321800_R181","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr, Skinner D, Sparkman KL. Discovering fragile X syndrome: family experiences and perceptions. Pediatrics.\u20082003;111(2):407\u2013416","DOI":"10.1542\/peds.111.2.407"},{"key":"2021120905122321800_R182","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr. Newborn screening for fragile X syndrome. Ment Retard Dev Disabil Res Rev.\u20082004;10(1):3\u201310","DOI":"10.1002\/mrdd.20002"},{"key":"2021120905122321800_R183","doi-asserted-by":"crossref","unstructured":"Bailey DB Jr, Skinner D, Davis AM, Whitmarsh I, Powell C. Ethical, legal, and social concerns about expanded newborn screening: fragile X syndrome as a prototype for emerging issues. Pediatrics.\u20082008;121(3). Available at: www.pediatrics.org\/cgi\/content\/full\/121\/3\/e693","DOI":"10.1542\/peds.2007-0820"},{"key":"2021120905122321800_R184","doi-asserted-by":"crossref","unstructured":"Strom CM, Huang D, Li Y, et al. Development of a novel, accurate, automated, rapid, high-throughput technique suitable for population-based carrier screening for fragile X syndrome. Genet Med.\u20082007;9(4):199\u2013207","DOI":"10.1097\/GIM.0b013e31803d3ac9"},{"key":"2021120905122321800_R185","doi-asserted-by":"crossref","unstructured":"Tassone F, Pan R, Amiri K, Taylor AK, Hagerman PJ. A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR1) gene in newborn and high-risk populations. J Mol Diagn.\u20082008;10(1):43\u201349","DOI":"10.2353\/jmoldx.2008.070073"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/123\/1\/378\/1124924\/zpe00109000378.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/123\/1\/378\/1124924\/zpe00109000378.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T15:14:34Z","timestamp":1738854874000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/123\/1\/378\/71987\/Advances-in-the-Treatment-of-Fragile-X-Syndrome"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1,1]]},"references-count":185,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2009,1,1]]},"published-print":{"date-parts":[[2009,1,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2008-0317","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1,1]]}}}