Skip to main content
SpringerLink
Log in

Fragile X Syndrome

  • Reference work entry
  • First Online:
Atlas of Genetic Diagnosis and Counseling

  • 403 Accesses

Abstract

Fragile X syndrome is the most common form of heritable intellectual disability, affecting approximately 1 in 1,250 males and 1 in 2,000 females (Webb 1989). The prevalence appears to be 1 in 4,000–6,000 males and 1 in 8,000–10,000 females. Martin and Bell first documented X-linked mental retardation in 1943. Subsequent identification of a fragile site on the long arm of the X chromosome (Lubs 1969), discovery of cell culture medium-dependent fragile site, and recognition of a unique constellation of physical features served to distinguish fragile X syndrome from other X-linked mental retardation syndromes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • American Academy of Pediatrics. (1996). Health supervision for children with fragile X syndrome. Pediatrics, 98, 297–300.

    Google Scholar 

  • Bardoni, B., Mandel, J. L., & Fisch, G. S. (2000). FMR1 gene and fragile X syndrome. American Journal of Medical Genetics (Seminars in Medical Genetics), 97, 153–163.

    Article  CAS  Google Scholar 

  • Berry-Kravis, E., Sumis, A., Hervey, C., et al. (2012). Clinic-based retrospective analysis of psychopharmacology for behavior in fragile X syndrome. International Journal of Pediatrics, 2012, 1–81.

    Article  Google Scholar 

  • Brown, W. T. (1995). Perspectives and molecular diagnosis of the fragile X syndrome. Clinics in Laboratory Medicine, 15, 859–875.

    CAS  PubMed  Google Scholar 

  • Brown, S. S. G., & Stanfield, A. C. (2015). Fragile X premutation carriers: A systematic review of neuroimaging findings. Journal of the Neurological Sciences, 352, 19–28.

    Article  PubMed  Google Scholar 

  • Caskey, C. T., Pizzuti, A., Fu, Y.-H., et al. (1992). Triplet repeat mutations in human disease. Science, 256, 784–789.

    Article  CAS  PubMed  Google Scholar 

  • Crawford, D. C., Acuna, J. M., & Sherman, S. L. (2001). FMR1 and the fragile X syndrome: Human genome epidemiology review. Genetics in Medicine, 3, 359–371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Das, S., Kubota, T., Song, M., et al. (1997). Methylation analysis of the fragile X syndrome by PCR. Genetic Testing, 1, 151–155.

    Article  CAS  PubMed  Google Scholar 

  • Davenport, M. H., Schaefer, T. L., Friedmann, K. J., et al. (2016). Pharmacotherapy for fragile X syndrome: Progress to date. Drugs, 76, 431–445.

    Article  CAS  PubMed  Google Scholar 

  • Davids, J. R., Hagerman, R. J., & Eilert, R. E. (1990). Orthopaedic aspects of fragile-X syndrome. Journal of Bone and Joint Surgery (America), 72, 889–896.

    Article  CAS  Google Scholar 

  • De Boulle, K., Verkerk, A. J. M. H., Reyniers, E., et al. (1993). A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nature Genetics, 3, 31–35.

    Article  PubMed  Google Scholar 

  • De Vries, B. B., Halley, D. J., Oostra, B. A., et al. (1998). The fragile X syndrome. Journal of Medical Genetics, 35, 579–589.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dyer-Friedman, J., Glaser, B., & Hessl, D. (2002). Genetic and environmental influences on the cognitive outcomes of children with fragile X syndrome. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 237–244.

    Article  PubMed  Google Scholar 

  • Dykens, E. M., Hodapp, R. M., & Leckman, J. F. (1994). Behavior and development in fragile X syndrome. Thousand Oaks: Sage.

    Google Scholar 

  • Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., et al. (1991). Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox. Cell, 67, 1047–1058.

    Article  CAS  PubMed  Google Scholar 

  • Goldson, E., & Hagerman, R. J. (1992). The fragile X syndrome. Developmental Medicine and Child Neurology, 34, 822–832.

    Google Scholar 

  • Hagerman, R. J. (2001). Fragile X syndrome. In S. B. Cassidy & J. E. Allanson (Eds.), Management of genetic syndromes. New York: Wiley-Liss.

    Google Scholar 

  • Hagerman, R. J., & Cronister, A. (Eds.). (1996). Fragile X syndrome: Diagnosis, treatment, and research. Baltimore: Johns Hopkins University Press.

    Google Scholar 

  • Hagerman, R., & Hagerman, P. (2013). Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurology, 12, 786–798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hagerman, R. J., & Silverman, A. C. (1991). Fragile X syndrome. Diagnosis, treatment, and research. Baltimore: Johns Hopkins University Press.

    Google Scholar 

  • Hagerman, R. J., Jackson, C., Amiri, K., et al. (1992). Girls with fragile X syndrome: Physical and neurocognitive status and outcome. Pediatrics, 89, 395–400.

    CAS  PubMed  Google Scholar 

  • Hagerman, R. J., Hull, C. E., Safanda, J. F., et al. (1994). High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. American Journal of Medical Genetics, 51, 298–308.

    Article  CAS  PubMed  Google Scholar 

  • Hagerman, R. J., Kimbro, L. T., & Taylor, A. K. (1998). Fragile X syndrome: A common cause of mental retardation and premature menopause. Contemporary OB/GYN, 43, 47–70.

    Google Scholar 

  • Hammond, L. S., Macias, M. M., Tarleton, J. C., et al. (1997). Fragile X syndrome and deletions in FMR1: New case and review of the literature. American Journal of Medical Genetics, 72, 430–434.

    Article  CAS  PubMed  Google Scholar 

  • Holden, J. J. A., Percy, M., Allingham-Hawkins, D., et al. (1999). Eighth international workshop on the fragile X syndrome and X-linked mental retardation. American Journal of Medical Genetics, 83, 221–236. August 16-22, 1997.

    Article  CAS  PubMed  Google Scholar 

  • Kallinen, J., Heinonen, S., Mannermaa, A., et al. (2000). Prenatal diagnosis of fragile X syndrome and the risk of expansion of a permutation. Clinical Genetics, 58, 111–115.

    Article  CAS  PubMed  Google Scholar 

  • Kau, A. S. M., Meyer, W. A., & Kaufmann, W. E. (2002). Early development in males with fragile X syndrome: A review of the literature. Microscopy Research and Technique, 57, 174–178.

    Article  PubMed  Google Scholar 

  • Kaufmann, W. E., & Reiss, A. L. (1999). Molecular and cellular genetics of fragile X syndrome. American Journal of Medical Genetics, 88, 11–24.

    Article  CAS  PubMed  Google Scholar 

  • Kenneson, A., & Warren, S. T. (2001). The female and the fragile X reviewed. Seminars in Reproductive Medicine, 19, 159–165.

    Article  CAS  PubMed  Google Scholar 

  • Laxova, R. (1994). Fragile X syndrome. Advances in Pediatrics, 41, 305–342.

    CAS  PubMed  Google Scholar 

  • Lozano, R., Rosero, C. A., & Hagerman, R. J. (2014). Fragile X spectrum disorders. Intractable & Rare Diseases Research, 3, 134–146.

    Article  Google Scholar 

  • Lubs, H. A. (1969). A marker X chromosome. American Journal of Human Genetics, 21, 231–244.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Musci, T. J., & Moyer, K. (2010). Prenatal carrier testing for fragile X: Counseling issues and challenges. Obstetrics and Gynecology Clinics of North America, 37, 61–70.

    Article  PubMed  Google Scholar 

  • Naber, S. P. (1995). Molecular diagnosis of fragile X syndrome. Diagnostic Molecular Pathology, 4, 158–161.

    Article  CAS  PubMed  Google Scholar 

  • Nolin, S. L., Brown, W. T., Glicksman, A., et al. (2003). Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. American Journal of Human Genetics, 72, 454–464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oostra, B. A., & Willemsen, R. (2001). Diagnostic tests for fragile X syndrome. Expert Review of Molecular Diagnostics, 1, 226–232.

    Article  CAS  PubMed  Google Scholar 

  • Oostra, B. A., Jacky, P. B., Brown, W. T., et al. (1993). Guidelines for the diagnosis of fragile X syndrome. Journal of Medical Genetics, 30, 410–413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Opitz, J. M. (1986). On the gates of hell and a most unusual gene (editorial). American Journal of Medical Genetics, 23, 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Park, V., Howard-Peebles, P., Sherman, S., et al. (1994). Fragile X syndrome: Diagnostic and carrier testing. American Journal of Medical Genetics, 53, 380–381.

    Article  Google Scholar 

  • Rousseau, F., Heitz, D., Biancalana, V., et al. (1991). Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. The New England Journal of Medicine, 325, 1673–1681.

    Article  CAS  PubMed  Google Scholar 

  • Saul, R. A., & Tarleton, J. C. (2012). FMR1-related disorders. GeneReviews. Updated 26 Apr 2012. Available at http://www.ncbi.nlm.nih.gov/books/NBK1384/

  • Schaefer, T. L., Davenport, M. H., & Erickson, C. A. (2015). Emerging pharmacologic treatment options for fragile X syndrome. The Application of Clinical Genetics, 8, 75–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sherman, S. L., Morton, N. E., Jacobs, P. A., et al. (1984). The marker (X) syndrome: A cytogenetic and genetic analysis. Annals of Human Genetics, 48, 21–37.

    Article  CAS  PubMed  Google Scholar 

  • Sherman, S. L., Jacobs, P. A., Morton, N. E., et al. (1985). Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Human Genetics, 69, 289–299.

    Article  CAS  PubMed  Google Scholar 

  • Sherman, S., Pletcher, B. A., & Driscoll, D. A. (2005). Fragile X syndrome: Diagnostic and carrier testing. Genetics in Medicine, 7, 584–587.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tarleton, J. C., & Saul, R. A. (1993). Molecular genetic advances in fragile X syndrome. Journal of Pediatrics, 122, 169–185.

    Article  CAS  PubMed  Google Scholar 

  • Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., 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.

    Article  CAS  PubMed  Google Scholar 

  • Warren, S. T., & Nelson, D. L. (1994). Advances in molecular analysis of fragile X syndrome. Journal of the American Medical Association, 271, 536–542.

    Article  CAS  PubMed  Google Scholar 

  • Webb, T. (1989). The epidemiology of the fragile X syndrome. In K. E. Davis (Ed.), The fragile X syndrome (pp. 40–55). Oxford: Oxford University Press.

    Google Scholar 

  • Willemsen, R., & Oostra, B. A. (2000). FMRP detection assay for the diagnosis of the fragile X syndrome. American Journal of Medical Genetics (Seminars in Medical Genetics), 97, 183–188.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Genetics, Shriners Hospitals for Children, Perinatal and Clinical Genetics, Department of Pediatrics, LSU Health Sciences Center, Shreveport, LA, USA

    Harold Chen

Authors
  1. Harold Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this entry

Cite this entry

Chen, H. (2017). Fragile X Syndrome. In: Atlas of Genetic Diagnosis and Counseling. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2401-1_96

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2401-1_96

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-2400-4

  • Online ISBN: 978-1-4939-2401-1

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation