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Genetic Counseling for FXTAS and FMR1-Associated Disorders

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Book cover The Fragile X-Associated Tremor Ataxia Syndrome (FXTAS)

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Abstract

Since its identification in 2001, awareness of fragile X-associated tremor/ataxia syndrome (FXTAS) has increased. The number of patients and families impacted by the condition continues to grow. Families with and without a history of fragile X syndrome (FXS) are impacted. Patients are usually identified based on their neurological findings such as intentional tremor, balance and gait difficulties, cognitive impairment, and brain MRI abnormalities.

Don’t let a sense of desperation overtake you. You can have a good and happy life despite FXTAS. Care for your loved one, but don’t forget to take care of yourself as well. …look for and cultivate something good in each day. Keep connected to your family and friends and build a support system. Remember to keep your sense of humor.

– Marilyn Darwin, wife of Richard (deceased)

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References

  • Alexopoulos, G. S., Raue, P., Arean, P. 2003. Problem-solving therapy versus supportive therapy in geriatric major depression with executive dysfunction. Am J Geriatr Psychiatry 11(1): 46–52.

    PubMed  Google Scholar 

  • Apessos, A., Abou-Sleiman, P. M., Harper, J. C., et al. 2001. Preimplantation genetic diagnosis of the fragile x syndrome by use of linked polymorphic markers. Prenat Diagn 21(6): 504–511.

    Article  PubMed  CAS  Google Scholar 

  • Aziz, M., Stathopulu, E., Callias, M., et al. 2003. Clinical features of boys with fragile x premutations and intermediate alleles. Am J Med Genet 121B(1): 119–127.

    Article  PubMed  Google Scholar 

  • Bacalman, S., Farzin, F., Bourgeois, J. A., et al. 2006. Psychiatric phenotype of the fragile x-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia. J Clin Psychiatry 67(1): 87–94.

    Article  PubMed  Google Scholar 

  • Bombard, Y., Penziner, E., Suchowersky, O., et al. 2008. Engagement with genetic discrimination: concerns and experiences in the context of Huntington disease. Eur J Hum Genet 16(3): 279–289.

    Article  PubMed  Google Scholar 

  • Bourgeois, J., Coffey, S., Rivera, S., et al. 2009. A review of Fragile x premutation disorders – expanding the psychiatric perspective. J Clin Psychiatry 70(6): 852–862.

    Google Scholar 

  • Bourgeois, J. A., Farzin, F., Brunberg, J. A., et al. 2006. Dementia with mood symptoms in a fragile x premutation carrier with the fragile x-associated tremor/ataxia syndrome: clinical intervention with donepezil and venlafaxine. J Neuropsychiatry Clin Neurosci 18(2): 171–177.

    Article  PubMed  Google Scholar 

  • Cameron, J. I., Cheung, A. M., Streiner, D. L., et al. 2006. Stroke survivors’ behavioral and psychologic symptoms are associated with informal caregivers’ experiences of depression. Arch Phys Med Rehabil 87(2): 177–183.

    Article  PubMed  Google Scholar 

  • Cameron, J. I., Franche, R. L., Cheung, A. M., et al. 2002. Lifestyle interference and emotional distress in family caregivers of advanced cancer patients. Cancer 94(2): 521–527.

    Article  PubMed  Google Scholar 

  • Castellvi Bel, S., Mila, M., Soler, A., et al. 1995. Prenatal diagnosis of fragile X syndrome: (CGG)n expansion and methylation of chorionic villus samples. Prenat Diagn 15(9): 801–807.

    Article  PubMed  CAS  Google Scholar 

  • Clifford, S., Dissanayake, C., Bui, Q. M., et al. 2007. Autism spectrum phenotype in males and females with fragile x full mutation and premutation. J Autism Dev Disord 37(4): 738–747.

    Article  PubMed  Google Scholar 

  • Coffey, S. M., Cook, K., Tartaglia, N., et al. 2008. Expanded clinical phenotype of women with the fmr1 premutation. Am J Med Genet A 146(8): 1009–1016.

    Google Scholar 

  • Cornish, K. M., Sudhalter, V., Turk, J. 2004. Attention and language in fragile x. Ment Retard Dev Disabil Res Rev 10(1): 11–16.

    Article  PubMed  Google Scholar 

  • Cran, D. G., Johnson, L. A. 1996. The predetermination of embryonic sex using flow cytometrically separated x and y spermatozoa. Hum Reprod Update 2(4): 355–363.

    Article  PubMed  CAS  Google Scholar 

  • Curlis, Y., Zhang, C., Holden, J. J., et al. 2005. Haplotype study of intermediate-length alleles at the fragile x (fmr1) gene: Atl1, fmrb, and microsatellite haplotypes differ from those found in common-size fmr1 alleles. Hum Biol 77(1): 137–151.

    Article  PubMed  Google Scholar 

  • de Jong, A., de Wert, G. 2002. Screening for carriers of the fragile x syndrome; ethical exploration. Ned Tijdschr Geneeskd 146(13): 611–615.

    PubMed  Google Scholar 

  • Farzin, F., Perry, H., Hessl, D., et al. 2006. Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile x premutation. J Dev Behav Pediatr 27(2 Suppl): S137–S144.

    Article  PubMed  Google Scholar 

  • Filipovic-Sadic, S., Sah, S., Chen, L., Krosting, J., Sekinger, E., Zhang, W., Hagerman, P. J., Stenzel, T. T., Hadd, A., Latham, G. J., & Tassone, F. 2010 Mar. A novel FMR1 PCR method for the routine detection of low-abundance expanded alleles and full mutations in fragile X syndrome. Clin Chem 56(3): 399–408.

    Google Scholar 

  • Gane, L. W., Flynn, L., Hagerman, R. J. 2005. Needs and priorities of FXTAS patients and spouses determined using q-sort methodology. Proceedings of the 12th International Workshop on Fragile X and X-Linked Mental Retardation, August 26–29, 2005, Williamsburg, VA.

    Google Scholar 

  • Geraedts, J. P., Harper, J., Braude, P., et al. 2001. Preimplantation genetic diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres. Prenat Diagn 21(12): 1086–1092.

    Article  PubMed  CAS  Google Scholar 

  • Goodlin-Jones, B., Tassone, F., Gane, L. W., et al. 2004. Autistic spectrum disorder and the fragile x premutation. J Dev Behav Pediatr 25(6): 392–398.

    Article  PubMed  Google Scholar 

  • Grasso, M., Faravelli, F., Nigro, C. L., et al. 1999. Mosaicism for the full mutation and a microdeletion involving the CGG repeat and flanking sequences in the fmr1 gene in eight fragile x patients. Am J Med Genet 85(3): 311–316.

    Article  PubMed  CAS  Google Scholar 

  • Grigsby, J., Brega, A. G., Jacquemont, S., et al. 2006. Impairment in the cognitive functioning of men with fragile x-associated tremor/ataxia syndrome (FXTAS). J Neurol Sci 248(1–2): 227–233.

    Article  PubMed  Google Scholar 

  • Grunfeld, E., Coyle, D., Whelan, T., et al. 2004. Family caregiver burden: results of a longitudinal study of breast cancer patients and their principal caregivers. CMAJ 170(12): 1795–1801.

    PubMed  Google Scholar 

  • Hagerman, P. J., Hagerman, R. J. 2004. The fragile-x premutation: a maturing perspective. Am J Hum Genet 74(5): 805–816.

    Article  PubMed  CAS  Google Scholar 

  • Hagerman, R. J. 2006. Lessons from fragile x regarding neurobiology, autism, and neurodegeneration. J Dev Behav Pediatr 27(1): 63–74.

    Article  PubMed  Google Scholar 

  • Hagerman, R. J., Hall, D. A., Coffey, S., et al. 2008. Treatment of fragile x-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin Interv Aging 3(2): 251–262.

    PubMed  Google Scholar 

  • Hessl, D., Glaser, B., Dyer-Friedman, J., et al. 2006. Social behavior and cortisol reactivity in children with fragile x syndrome. J Child Psychol Psychiatry 47(6): 602–610.

    Article  PubMed  Google Scholar 

  • Hessl, D., Tassone, F., Loesch, D. Z., et al. 2005. Abnormal elevation of fmr1 mRNA is associated with psychological symptoms in individuals with the fragile x premutation. Am J Med Genet B Neuropsychiatr Genet 139(1): 115–121.

    Google Scholar 

  • Jacquemont, S., Farzin, F., Hall, D., et al. 2004a. Aging in individuals with the fmr1 mutation. Am J Ment Retard 109(2): 154–164.

    Article  PubMed  CAS  Google Scholar 

  • Jacquemont, S., Hagerman, R. J., Leehey, M. A., et al. 2003. Penetrance of the fragile x-associated tremor/ataxia syndrome (FXTAS) in a premuation carrier population: initial results from a California family-based study. Proceedings of the 53rd Annual Meeting, Los Angeles, CA. Am J Hum Genet 73(Suppl 5)A10: 163.

    Google Scholar 

  • Jacquemont, S., Hagerman, R. J., Leehey, M. A., et al. 2004b. Penetrance of the fragile x-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 291(4): 460–469.

    Article  PubMed  CAS  Google Scholar 

  • Keysor, C. S., Mazzocco, M. M. 2002. A developmental approach to understanding fragile x syndrome in females. Microsc Res Tech 57(3): 179–186.

    Article  PubMed  Google Scholar 

  • Leehey, M. A., Berry-Kravis, E., Min, S. J., et al. 2007. Progression of tremor and ataxia in male carriers of the fmr1 premutation. Mov Disord 22(2): 203–206.

    Article  PubMed  Google Scholar 

  • McConkie-Rosell, A., Abrams, L., Finucane, B., et al. 2007. Recommendations from multi-disciplinary focus groups on cascade testing and genetic counseling for fragile x-associated disorders. J Genet Couns 16(5): 593–606.

    Article  PubMed  Google Scholar 

  • Mila, M., Mallolas, J. 2001. Fragile x syndrome: premature ovarian failure. Preimplantation and preconception genetic diagnosis. Rev Neurol 33(Suppl 1): S20–S23.

    PubMed  Google Scholar 

  • Nolin, S. L., Brown, W. T., Glicksman, A., et al. 2003a. Expansion of the fragile x CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet 72(2): 454–464.

    Article  PubMed  CAS  Google Scholar 

  • Nolin, S. L., Dobkin, C., Brown, W. T. 2003b. Molecular analysis of fragile x syndrome. Curr Protoc Hum Genet Chapter 9: Unit9.5.

  • Nolin, S. L., Lewis, F. A., 3rd, Ye, L. L., et al. 1996. Familial transmission of the fmr1 CGG repeat. Am J Hum Genet 59(6): 1252–1261.

    PubMed  CAS  Google Scholar 

  • NSGC. 2005. Retrieved 12/1/2008, from http://www.nsgc.org/consumer/definitions.cfm

  • Penagarikano, O., Mulle, J. G., Warren, S. T. 2007. The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 8: 109–129.

    Article  PubMed  CAS  Google Scholar 

  • Platteau, P., Sermon, K., Seneca, S., et al. 2002. Preimplantation genetic diagnosis for fragile xa syndrome: difficult but not impossible. Hum Reprod 17(11): 2807–2812.

    Article  PubMed  Google Scholar 

  • Pozdnyakova, I., Regan, L. 2005. New insights into fragile x syndrome. Relating genotype to phenotype at the molecular level. FEBS J 272(3): 872–878.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, J. E., Bailey, D. B., Jr., Mankowski, J., et al. 2008. Mood and anxiety disorders in females with the fmr1 premutation. Am J Med Genet B Neuropsychiatr Genet 147B: 1138–1144.

    Article  Google Scholar 

  • Seritan, A. L., Nguyen, D. V., Farias, S. T., et al. 2008. Dementia in fragile x-associated tremor/ataxia syndrome (FXTAS): comparison with Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 147B(7): 1138–1144.

    Article  PubMed  Google Scholar 

  • Sherman, S. L., Taylor, K., Allen, E. G. 2007. Fmr1 premutation: a leading cause of inherited ovarian dysfunction.In Fragile sites: new discoveries and changing perspectives. I. Arrieta. Hauppauge, NY: Nova Science Publishers, pp. 299–320.

    Google Scholar 

  • Tassone, F., Adams, J., Berry-Kravis, E. M., et al. 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 

  • Tassone, F., Hagerman, R. J., Taylor, A. K., et al. 2000. Elevated levels of fmr1 mRNA in carrier males: a new mechanism of involvement in the fragile-x syndrome. Am J Hum Genet 66(1): 6–15.

    Article  PubMed  CAS  Google Scholar 

  • Tassone, F., Pan, R., Amiri, K., et al. 2008. 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 10(1): 43–49.

    Article  PubMed  CAS  Google Scholar 

  • Wingrove, K. J., Norris, J., Barton, P. L., et al. 1996. Experiences and attitudes concerning genetic testing and insurance in a Colorado population: a survey of families diagnosed with fragile x syndrome. Am J Med Genet 64(2): 378–381.

    Article  PubMed  CAS  Google Scholar 

  • Wirojanan, J., Angkustsiri, K., Tassone, F., et al. 2008. A girl with fragile x premutation from sperm donation. Am J Med Genet A 146(7): 888–892.

    PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Robert Hendren, Theresa Contenti, and Beverly Wardlaw for their continued support and efforts on behalf of our development work for fragile X-associated disorders. We thank Page Sorensen, junior specialist, for her work on this chapter as without her we would not have been able to complete the many details. We would also like to thank all the patients who have been diagnosed with FXTAS, those diagnosed with fragile X syndrome, and their many family members including those who have made contributions to this chapter. It is because of each of them that we continue to learn, change, and grow in our understanding of fragile X-associated disorders.

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Authors and Affiliations

  1. UC Davis M.I.N.D. Institute, University of California, Sacramento, CA, USA

    Louise W. Gane

  2. University of Colorado Health Sciences Center, Aurora, CO, USA

    Katherine Howard

  3. National Fragile X Foundation, Walnut Creek, CA, USA

    Liane Abrams

Authors
  1. Louise W. Gane
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  2. Katherine Howard
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  3. Liane Abrams
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Corresponding author

Correspondence to Louise W. Gane .

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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

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Gane, L.W., Howard, K., Abrams, L. (2010). Genetic Counseling for FXTAS and FMR1-Associated Disorders. 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_10

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