Skip to main content
SpringerLink
Log in
Book cover

The Fragile X-Associated Tremor Ataxia Syndrome (FXTAS) pp 17–30Cite as

The Epidemiology of FXTAS

  • Chapter
  • First Online:

Abstract

The prevalence of the FMR1 premutation ranges from 1/116 to 1/259 in women and from 1/251 to 1/1,250 in men. Population studies investigating the prevalence of FXTAS in the general population have not been conducted due to the rarity of the disorder. The prevalence of FXTAS is estimated to be 1/4,000 in men over the age of 55, due to age-dependent penetrance. The prevalence in women is thought to be much lower, at approximately 1/7,800, because of the protection of the second X chromosome. Many screening studies have been conducted in movement disorder populations, attempting to ascertain undiagnosed FXTAS cases and premutation expansions. These studies have yielded low rates, with a rate of 1.3% in cerebellar ataxia patients, <1% in parkinsonian disorders, such as Parkinson disease and multiple system atrophy, and 0% in essential tremor. Screening studies vary widely in the type of patients included, both in ethnicity and in gender. Wider inclusion criteria for screening should increase the rates of ascertainment of both FXTAS and premutation expansions in future studies.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Annesi, G. N., Tarantino, P., Cutuli, N., Annesi, F., Marco, E. V., Zappia, M., Morgante, L., Arabia, G., Pugliese, P., Condino, F., Carrideo, S., Civitelli, D., Caracciolo, M., Romeo, N., Spadafora, P., Candiano, I. C., Quattrone, A. 2004. FRAXE intermediate alleles are associated with Parkinson’s disease. Neurosci Lett 368: 21–24.

    Article  PubMed  CAS  Google Scholar 

  • Arocena, D. G., Louis, E. D., Tassone, F., Gilliam, T. C., Ottman, R., Jacquemont, S., Hagerman, P. J. 2004. Screen for expanded FMR1 alleles in patients with essential tremor. Mov Disord 19: 930–947.

    Article  Google Scholar 

  • Berkenstadt, M., Ries-Levavi, L., Cuckle, H., Peleg, L., Barkai, G. 2007. Preconceptional and prenatal screening for fragile X syndrome: experience with 40,000 tests. Prenat Diagn 27: 991–994.

    Article  PubMed  Google Scholar 

  • Berry-Kravis, E., Potanos, K., Weinberg, D., Zhou, L., Goetz, C. G. 2005. Fragile x-associated tremor/ataxia syndrome in sisters related to X-inactivation. Ann Neurol 57: 144–147.

    Article  PubMed  CAS  Google Scholar 

  • Biancalana, V., Toft, M., Le Ber, I., Tison, F., Scherrer, E., Thibodeau, S., Mandel, J. L., Brice, A., Farrer, M. J., Dürr, A. 2005. FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. Arch Neurol 62: 962–966.

    Article  PubMed  Google Scholar 

  • Brusse, E., Maat-Kievit, J. A., van Swieten, J. C. 2007. Diagnosis and management of early- and late-onset cerebellar ataxia. Clin Genet 71: 12–24.

    Article  PubMed  CAS  Google Scholar 

  • Brussino, A., Gellera, C., Saluto, A., Mariotti, C., Arduino, C., Castelloti, B., Camerlingo, M., de Angelis, V., Orsi, L., Tosca, P., Migone, N., Taroni, F., Brusco, A. 2005. FMR1 gene premutation is a frequent cause of late-onset sporadic cerebellar ataxia. Neurology 64: 145–147.

    Article  PubMed  CAS  Google Scholar 

  • Cilia, R., Kraff, J., Canesi, M., Pezzoli, G., Goldwurm, S., Amiri, K., Tang, H. T., Pan, R., Hagerman, P. J., Tassone, F. 2009. Screening for the presence of FMR1 premutation alleles in women with parkinsonism. Arch Neurol 66(2): 244–249.

    Google Scholar 

  • Coffey, S. M., Cook, K., Tartaglia, N., Tassone, F., Nguyen, D. V., Pan, R., Bronsky, H. E., Yuhas, J., Borodyanskaya, M., Grigsby, J., Doerflinger, M., Hagerman, P. J., Hagerman, R. J. 2008. Expanded clinical phenotype of women with the FMRl premutation. Am J Med Genet A, 146(8): 1009–1016.

    Google Scholar 

  • Crawford, D. C., Meadows, K. L., Newman, J. L., Taft, L. F., Scott, E., Leslie, M., Shubek, L., Holmgreen, P., Yeargin-Allsopp, M., Boyle, C., Sherman, S. L. 2002. Prevalence of the fragile X syndrome in African Americans. Am J Med Genet 110: 226–233.

    Article  PubMed  Google Scholar 

  • Deng, H., Jankiovic, J. 2004. Premutation alleles associated with Parkinson disease and essential tremor. JAMA 292: 1685–1688.

    Article  PubMed  CAS  Google Scholar 

  • Dombrowski, C., Levesque, S., Morel, M. L., Rouillard, P., Morgan, K., Rousseau, F. 2002. Premutation and intermediate-size FMR1 alleles in 10,572 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 11: 371–378.

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Carvajal, I., Walichiewicz, P., Xiaosen, X., Pan, R., Hagerman, P. J., Tassone, F. 2009. Screening for expanded alleles for the FMR1 gene in blood spots from newborn males in a Spanish population. J Mol Diagn 11(4): 324–329.

    Article  PubMed  CAS  Google Scholar 

  • Garland, E. M., Vmencak-Jones, C., Biaggioni, I., Davis, T. L., Montine, T. J., Robertson, D. 2004. Fragile X gene premutation in multiple system atrophy. J Neurol Sci 227: 115–118.

    Article  PubMed  CAS  Google Scholar 

  • Geva, E., Yaron, Y., Shomrat, Y., Ben-Yehuda, A., Zabari, S., Peretz, H., Naiman, T., Yeger, H., Orr-Urtreger, A. September 1, 2000. The risk of fragile X premutation expansion is lower in carriers detected by general prenatal screening than in carriers from known fragile X families. Genet Test 4(3): 289–292.

    Article  PubMed  CAS  Google Scholar 

  • Hagerman, H. 2008. The fragile X prevalence paradox. J Med Genet 45(8): 498–499. 10.1136/jmg.2008.059055.

    Article  PubMed  Google Scholar 

  • Hagerman, R. J., Leavitt, B. R., Farzin, F., Jacquemont, S., Greco, C. M., Brunberg, J. A., Tassone, F., Hessl, D., Harris, S. W., Zhang, L., Jardini, T., Gane, L. W., Ferranti, J., Ruiz, L., Leehey, M. A., Grigsby, J., Hagerman, P. J. 2004. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 74: 1051–1056.

    Article  PubMed  CAS  Google Scholar 

  • Hall, D. A., Berry-Kravis, E., Jacquemont, S., Rice, C. D., Cogswell, J., Zhang, L., Hagerman, R., Hagerman, P. J., Leehey, M. A. 2005. Prior diagnosis given to persons with the fragile X-associated tremor/ataxia syndrome. Neurology 65: 299–301.

    Article  PubMed  CAS  Google Scholar 

  • Hall, D. A., Hagerman, R. J., Hagerman, P. J., Jacquemont, S., Leehey, M. A. 2006. Prevalence of FMR1 repeat expansions in movement disorders: a systematic review. Neuroepidemiology 26: 151–155.

    Article  PubMed  CAS  Google Scholar 

  • Hall, D. A., Howard, K., Hagerman, R. J., Leehey, M. A. 2009. Parkinsonism in FMR1 premutation carriers May be indistinguishable from Parkinson disease. Park Rel Dis 15: 156–159.

    Article  Google Scholar 

  • Hedrich, K., Pramstaller, P. P., Stübke, K., Hiller, A., Kabakci, K., Purmann, S., Kasten, M., Scaglione, C., Schwinger, E., Volkmann, J., Kostic, V., Vieregge, P., Martinelli, P., Abbruzzese, G., Klein, C., Zühlke, C. 2005. Premutations in the FMR1 gene as a modifying factor in parkin-associated Parkinson’s disease? Mov Disord 20(8): 1060–1062.

    Article  PubMed  Google Scholar 

  • Jacquemont, S., Hagerman, R., Leehey, M. A., Hall, D. A., Levine, R. A., Brunberg, J. A., Zhang, L., Jardini, T., Gane, L. W., Harris, S. W., Herman, K., Grigsby, J., Greco, C. M., Berry-Kravis, E., Tassone, F., Hagerman, P. J. 2004. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 291(4): 460–469.

    Article  PubMed  CAS  Google Scholar 

  • Jacquemont, S., Leehey, M. A., Hagerman, R. J., Beckett, L. A., Hagerman, P. J. 2006. Size bias of fragile X premutation alleles in late-onset movement disorders. J Med Genet 43(10): 804–809.

    Article  PubMed  CAS  Google Scholar 

  • Kamm, C., Healy, D., Quinn, N. P., Wullner, U., Moller, J. C., Schols, L., Geser, F., Burk, K., Borglum, A. D., Pellecchia, M. T., Tolosa, E., del Sorbo, F., Nilsson, C., Bandmann, O., Sharma, M., Mayer, P., Gasteiger, M., Haworth, A., Ozawa, T., Lees, A. J., Short, J., Guinti, P., Holinski-Feder, E., Illig, T., Wichmann, H. E., Wenning, G. K., Wood, N. W., Gasser, T. 2005. The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA study group. Brain 128: 1855–1860.

    Article  PubMed  CAS  Google Scholar 

  • Kerber, K. A., Jen, J., Perlman, S., Baloh, R. 2005. Late-onset pure cerebellar ataxia: differentiating those with and without identifiable mutations. J Neurol Sci 238: 41–45.

    Article  PubMed  CAS  Google Scholar 

  • Kraff, J., Tang, H., Cilia, R., Canesi, M., Pezzoli, G., Goldwurm, S., Hagerman, P. J., Tassone, F. 2007. Screen for excess FMR1 premutation alleles among males with parkinsonism. Arch Neurol 64(7): 1002–1006.

    Article  PubMed  Google Scholar 

  • Kraft, S., Furtado, S., Ranawaya, R., Parboosingh, J., Bleoo, S., McElligott, K., Bridge, P., Spacey, S., Das, S., Suchowersky, O. 2005. Adult onset spinocerebellar ataxia in a Canadian movement disorders clinic. Can J Neurol Sci 32(4): 450–458.

    PubMed  Google Scholar 

  • Leehey, M. A., Berry-Kravis, E., Goetz, C., Zhang, L., Hall, D. A., Li, L., Rice, C. D., Lara, R., Cogswell, J. B., Reynolds, A., Gane, L., Jacquemont, S., Tassone, F., Grigsby, J., Hagerman, R. J., Hagerman, R. J. 2008. FMR1 CGG repeat length predicts motor dysfunction in FXTAS. Neurology 70: 1397–1402.

    Article  PubMed  CAS  Google Scholar 

  • MacPherson, J., Waghorn, A., Hammans, S., Jacobs, P. 2003. Observation of an excess of fragile-X premutations in a population of males referred with spinocerebellar ataxia. Hum Genet 112: 619–620.

    PubMed  CAS  Google Scholar 

  • Milunsky, J. M., Maher, T. A. 2004. Fragile X carrier screening and spinocerebellar ataxia in older males. Am J Med Genet A 125A(3): 320.

    Google Scholar 

  • Pesso, R., Berkenstadt, M., Cuckle, H., Gak, E., Peleg, L., Frydman, M., Barkai, G. 2000. Screening for fragile X syndrome in women of reproductive age. Prenat Diagn 20: 611–614.

    Article  PubMed  CAS  Google Scholar 

  • Reis, A. H., Ferreira, A., Gomes, K. B., Aguiar, M. J., Fonseca, C. G., Cardoso, F. E., Pardini, V. C., Carvalho, M. R. 2008. Frequency of FMR1 premutation in individuals with ataxia and/or tremor and/or parkinsonism. Genet Mol Res 7(1): 74–84.

    Article  PubMed  CAS  Google Scholar 

  • Rife, M., Badenas, C., Mallolas, J., Jimenez, L., Cervera, R., Maya, A., Glover, G., Rivera, F., Mila, M. 2003. Incidence of fragile X in 5,000 consecutive newborn males. Genet Test 7: 339–343.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Revenga, L., Gomez-Anson, B., Muñoz, E., Jiménez, D., Santos, M., Tintoré, M., Martín, G., Brieva, L., Milà, M. 2007. FXTAS in Spanish patients with ataxia: support for female FMR1 premutation screening. Mol Neurobiol 35(3): 324–328.

    Article  PubMed  CAS  Google Scholar 

  • Rousseau, F., Rouillard, P., Morel, M., Khandjian, E. W., Morgan, K. 1995. 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 57: 1006–1018.

    PubMed  CAS  Google Scholar 

  • Ryynanen, M., Heinonen, S., Makkonen, M., Kajanoja, E., Mannermaa, A., Pertti, K. 1999. Feasibility and acceptance of screening for fragile X mutations in low-risk pregnancies. Eur J Hum Genet 7: 212–216.

    Article  PubMed  CAS  Google Scholar 

  • Saul, R. A., Friez, M., Eaves, K., Stapleton, G. A., Collins, J. S., Schwartz, C. E., Stevenson, R. E. 2008. Fragile X syndrome detection in newborns – pilot study. Genet Med 10(10): 714–719.

    PubMed  CAS  Google Scholar 

  • Seixas, A. I., Maurer, M., Lin, M., Callahan, C., Ahuja, A., Matsura, T., Ross, C. A., Hisama, F. M., Silveria, E., Margolis, R. L. 2005. FXTAS, SCA10, and SCA17 in American patients with movement disorders. Am J Med Genet A 136(1): 87–89.

    PubMed  Google Scholar 

  • Tan, E. K., Zhao, Y., Puong, K. Y., Law, H. Y., Chan, L. L., Yew, K., Shen, H., Chandran, V. R., Yuen, Y., Pavanni, R., Wong, M. C., Ng., I. S. 2005. Expanded FMR1 alleles are rare in idiopathic Parkinson’s disease. Neurogenetics 6(1): 51–52.

    Article  PubMed  CAS  Google Scholar 

  • Tan, E. K., Zhao, Y., Puong, K. Y., Law, H. Y., Chan, L. L., Yew, K., Tan, C., Shen, H., Chandran, V. R., Teoh, M. L., Yih, Y., Pavanni, R., Wong, M. C., Ng, I. S. 2004. Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort. Neurology 63: 362–363.

    Article  PubMed  CAS  Google Scholar 

  • Tassone, F., Adams, J., Berry-Kravis, E., Cohen, S., Brusco, A., Leehey, M. A., Li, L., Hagerman, R. J., Hagerman, P. J. 2007. CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ataxia syndrome (FXTAS). Am J Med Genet B Neuropsychiatr Genet 144(4): 566–569.

    Google Scholar 

  • Toft, M., Aasley, J., Bisceglio, G., Adler, C. H., Uitti, R. J., Krygowska-Wajs, A., Lynch, T., Wszolek, Z. K., Farrer, M. J. 2005. Parkinsonism, FXTAS, and FMR1 premutations. Mov Disord 20: 230–233.

    Article  PubMed  Google Scholar 

  • Toledano-Alhadef, H., Basel-Vanagaite, L., Magal, N., Davidov, B., Ehrlich, S., Drasinover, V., Taub, E., Halpern, G. J., Ginott, N., Shohat, M. 2001. Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet 69(2): 351–360.

    Article  PubMed  CAS  Google Scholar 

  • Tzeng, C., Tsai, L., Hwu, W., Lin, S., Chao, M., Jong, Y., Chu, S. Y., Chao, W. C., Lu, C. L. 2005. Prevalence of the FMR1 mutation in Taiwan assessed by large-scale screening of newborn boys and analysis of DXS548-FRAXAC1 haplotype. Am J Med Genet A 133: 37–43.

    Google Scholar 

  • Van Esch, H., Dom, R., Bex, D., Salden, I., Caeckebeke, J., Wibail, A., Borghgraef, M., Leguis, E., Fryns, J., Matthijs, G. 2005. Screening for FMR1 premutations in 122 older Flemish males presenting with ataxia. Euro J Hum Genet 13: 121–123.

    Article  Google Scholar 

  • Yabe, I., Soma, H., Takei, A., Fujik, N., Sasaki, H. 2004. No association between FMR1 premutations and multiple system atrophy. J Neurol 251(11): 1411–1412.

    Article  PubMed  Google Scholar 

  • Zühlke, C., Budnik, A., Gehlken, U., Dalski, A., Purmann, S., Naumann, M., Schmidt, M., Bürk, K., Schwinger, E. 2004. J Neurol 251(11): 1418–1419.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

    Deborah A. Hall

  2. Service de génétique, Centre Hospitalier Universitaire de Lausanne, Lausanne, Switzerland

    Sebastien Jacquemont

Authors
  1. Deborah A. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastien Jacquemont
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Deborah A. Hall .

Editor information

Editors and Affiliations

  1. Dept. Biochemistry & Molecular Medicine, University of California, Davis, Davis, 95616, California, USA

    Flora Tassone

  2. Medical Center, Dept. Pediatrics, Rush University, 1725 W. Harrison St., Suite 718, Chicago, 60612, Illinois, USA

    Elizabeth M. Berry-Kravis

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hall, D.A., Jacquemont, S. (2010). The Epidemiology of FXTAS. In: Tassone, F., Berry-Kravis, E. (eds) The Fragile X-Associated Tremor Ataxia Syndrome (FXTAS). Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5805-1_2

Download citation

Publish with us

Policies and ethics

Search

Navigation