Encyclopedia of Clinical Neuropsychology

Living Edition
| Editors: Jeffrey Kreutzer, John DeLuca, Bruce Caplan

Fragile X Syndrome

  • Frank J. Gallo
  • Bonita P. Klein-Tasman
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-56782-2_1548-2


Short Description or Definition

Fragile X (FXS) is a neurodevelopmental disorder that is caused by an unstable expansion (CGG repeats) in the FMR1 gene on the X chromosome. FXS is the most common form of inherited intellectual disability (ID). FXS in can result in physical features including prominent ears, elongated face, flat feet, macroorchidism (enlarged testicles in males), connective tissue abnormalities, and epilepsy, among others. Males are generally more severely affected than are females. In addition to ID and various cognitive weaknesses, high rates of autism spectrum disorder (ASD) and attention/deficit hyperactivity disorder (ADHD) have been identified.


Classification of FXS is based upon the size of CGG trinucleotide repeats within the FMR1 gene located on the X chromosome. In the general population, 6–55 repeats are routinely transmitted in a...

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Further Reading

  1. Berry-Kravis, E. (2002). Epilepsy in fragile X syndrome. Developmental Medicine and Child Neurology, 44, 724–728.CrossRefPubMedGoogle Scholar
  2. Birch, R. C., Cornish, K. M., Hocking, D. R., & Trollor, J. N. (2014). Understanding the neuropsychiatric phenotype of fragile X-associated tremor ataxia syndrome: A systematic review. Neuropsychology Review, 24(4), 491–513.  https://doi.org/10.1007/s11065-014-9262-9.CrossRefPubMedGoogle Scholar
  3. Braat, S., & Kooy, R. F. (2015). Insights into GABAAergic system deficits in fragile X syndrome lead to clinical trials. Neuropharmacology, 88, 48–54.  https://doi.org/10.1016/j.neuropharm.2014.06.028.CrossRefPubMedGoogle Scholar
  4. Chromik, L. C., Quintin, E. M., Lepage, J. F., Hustyi, K. M., Lightbody, A. A., & Reiss, A. L. (2015). The influence of hyperactivity, impulsivity, and attention problems on social functioning in adolescents and young adults with fragile X syndrome. Journal of Attention Disorders.  https://doi.org/10.1177/1087054715571739. [Epub ahead of print].PubMedPubMedCentralGoogle Scholar
  5. Cornish, K. M., Turk, J., Wilding, J., Sudhalter, V., Munir, F., Kooy, F., et al. (2004). Annotation: Deconstructing, the attention deficit in fragile X syndrome: A developmental neuropsychological approach. Journal of Child Psychology and Psychiatry, 46, 1042–1053.CrossRefGoogle Scholar
  6. Cornish, K. M., Lexin, L., Kogan, C. S., Jacquemont, S., Turk, J., Dalton, A., et al. (2008). Age-dependent cognitive changes in carriers of the fragile X syndrome. Cortex, 44, 628–636.CrossRefPubMedGoogle Scholar
  7. For more information on FXS, visit the National Fragile X Foundation website at http://www.fragilex.org
  8. Gothelf, D., Furfaro, J. A., Hoeft, F., Eckert, M. A., Hall, S. S., O’Hara, R., et al. (2007). Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). Annals of Neurology, 63, 40–51.CrossRefGoogle Scholar
  9. Hagerman, R. J. (2002). Physical and behavioral phenotype. In R. J. Hagerman & P. J. Hagerman (Eds.), Fragile X syndrome: Diagnosis, treatment and research (3rd ed., pp. 136–168). Baltimore: The Johns Hopkins University Press.Google Scholar
  10. Hagerman, R. J. (2008). Etiology, diagnosis, and development in fragile X syndrome. In J. E. Roberts, R. S. Chapman, & S. F. Warren (Eds.), Speech and language development and intervention in down syndrome and Fragile X syndrome (pp. 27–49). Baltimore: Paul H. Brookes Publishing.Google Scholar
  11. Hagerman, R. J., Leehey, M., Heinrichs, W., Tassone, F., Wilson, R., Hills, J., et al. (2001). Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology, 57, 127–130.CrossRefPubMedGoogle Scholar
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  14. Hoeft, F., Hernandez, A., Parthasarathy, S., Watson, C. L., Hall, S. S., & Reiss, A. L. (2007). Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome. Human Brain Mapping, 28, 543–554.CrossRefPubMedGoogle Scholar
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  16. Menon, V., Leroux, J., White, C. D., & Reiss, A. L. (2004). Frontostriatal deficits in fragile X syndrome: Relation to FMR1 gene expression. Proceedings of the National Academy of Sciences of the United States of America, 101, 3615–3620.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Philofsky, A., Hepburn, S. L., Hayes, A., Hagerman, R., & Rogers, S. J. (2004). Linguistic and cognitive functioning and autism symptoms in young children with fragile X syndrome. American Journal on Mental Retardation, 109, 208–218.CrossRefPubMedGoogle Scholar
  18. Quintin, E. M., Jo, B., Hall, S. S., Bruno, J. L., Chromik, L. C., Raman, M. M.,. .. Reiss, A. L. (2015). The cognitive developmental profile associated with fragile X syndrome: A longitudinal investigation of cognitive strengths and weaknesses through childhood and adolescence. Development and Psychopathology 1–13.  https://doi.org/10.1017/S0954579415001200 [pii]
  19. Schwarte, A. R. (2008). Fragile X syndrome. School Psychology Quarterly, 23, 290–300.CrossRefGoogle Scholar
  20. Sherman, S. (2002). Epidemiology. In R. J. Hagerman & P. J. Hagerman (Eds.), Fragile X syndrome: Diagnosis, treatment and research (3rd ed., pp. 136–168). Baltimore: The Johns Hopkins University Press.Google Scholar
  21. Verkerk, A. J., Pieretti, M., Sutcliff, J. S., Fu, Y. H., Kuhl, D. P., Pizzuti, A., et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905–914.CrossRefPubMedGoogle Scholar
  22. Zalfa, F., Achsel, T., & Bagni, C. (2006). mRNPs, polysomes or granules: FMRP in neuronal protein synthesis. Current Opinion in Neurobiology, 16, 265–269.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of Wisconsin-MilwaukeeMilwaukeeUSA