Journal of Genetic Counseling

, Volume 26, Issue 3, pp 501–510 | Cite as

A Pilot Study of Fragile X Syndrome Screening in Pregnant Women and Women Planning Pregnancy: Implementation, Acceptance, Awareness, and Geographic Factors

  • Ramona Alfaro Arenas
  • Jordi Rosell Andreo
  • Damián Heine Suñer
  • Group for the study of FXS in the Balearic Islands
Original Research


We report herein results of a study performed in the Balearic Islands which had the following goals: 1) Determine the proportion of pregnant or non-pregnant women planning pregnancy, who would choose to undergo a screening test for Fragile X Syndrome (FXS), if it is accompanied by the appropriate information; 2) Assess satisfaction and any increase in stress among women who participate in screening; 3) Collect epidemiological information about the incidence of the disease in our population; and 4) Collect demographic and health history data and assess participants’ awareness of the disease. Screening was performed on 3,731 pregnant and non-pregnant women of childbearing age and the results indicate: a very high voluntary rate of participation; a high level of self-reported satisfaction and low levels of stress because of the test; a very high incidence of premutation (1/106) in our population; and a low level of awareness about the existence of FXS (25 %). Additional findings indicate no significant correlation between self-reported health history and premutation detection, and the high premutation incidence does not seem to be specific to the indigenous Balearic population. Based on these results, we discuss the pros and cons of an implementation of preconception and pregnant women screening for FXS within a public health screening program.


Fragile X syndrome Intellectual disability Neurogenetic disorder Screening Reproductive genetics Stress Satisfaction Awareness 



We thank participants and professionals who contributed to this study. We also thank Natalia Marlowe, John Norton, Birgit Reinhardt, Koldo Aurrekoetxea and Judy H Yu from Abbott Molecular for their help.

Compliance with Ethical Standards

Conflict of Interest

Authors Ramona Alfaro Arenas, Jordi Rosell Andreo and Damián Heine Suñer have been funded by an Abbott Laboratories Inc. grant.

Human Studies and Informed Consent

‘All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.’

Animal Studies

No animal studies were carried out by the authors for this article.

Supplementary material

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  1. Abrams, L., Cronister, A., Brown, W. T., Tassone, F., Sherman, S. L., Finucane, B., et al. (2012). Newborn, carrier, and early childhood screening recommendations for fragile X. Pediatrics, 130(6), 1126–1135. doi: 10.1542/peds.2012-0693.CrossRefPubMedGoogle Scholar
  2. Alfaro Arenas, R., Rosell Andreo, J., Heine Suñer, D., & Group for the study of FXS in the Balearic Islands. (2016). Fragile X syndrome screening in pregnant women and women planning pregnancy shows a remarkably high FMR1 premutation prevalence in the Balearic Islands. American Journal of Medical Genetics. Part B, 9999, 1–9.Google Scholar
  3. Basehore, M. J., Marlowe, N. M., Jones, J. R., Behlendorf, D. E., Laver, T. A., & Friez, M. J. (2012). Validation of a screening tool for the rapid and reliable detection of CGG trinucleotide repeat expansions in FMR1. Genetic Testing and Molecular Biomarkers, 16(6), 465–470. doi: 10.1089/gtmb.2011.0134.CrossRefPubMedGoogle Scholar
  4. 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. Prenatal Diagnosis, 27(11), 991–994. doi: 10.1002/pd.1815.CrossRefPubMedGoogle Scholar
  5. Berry-Kravis, E. (2014). Mechanism-based treatments in neurodevelopmental disorders: fragile X syndrome. Pediatric Neurology, 50(4), 297–302. doi: 10.1016/j.pediatrneurol.2013.12.001.CrossRefPubMedGoogle Scholar
  6. Biancalana, V., Glaeser, D., McQuaid, S., & Steinbach, P. (2015). EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders. European Journal of Human Genetics, 23(4), 417–425.CrossRefPubMedGoogle Scholar
  7. Gutierrez, J. F., Bajaj, K., & Klugman, S. D. (2013). Prenatal screening for fragile X: carriers, controversies, and counseling. Reviews in Obstetrics & Gynecology, 6(1), e1–e7. doi: 10.3909/riog0203.Google Scholar
  8. Hantash, F. M., Goos, D. M., Crossley, B., Anderson, B., Zhang, K., Sun, W., et al. (2011). FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency i. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 13(1), 39–45. doi: 10.1097/GIM.0b013e3181fa9fad.CrossRefGoogle Scholar
  9. Hill, M. K., Archibald, A. D., Cohen, J., & Metcalfe, S. A. (2010). A systematic review of population screening for fragile X syndrome. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 12(7), 396–410. doi: 10.1097/GIM.0b013e3181e38fb6.CrossRefGoogle Scholar
  10. Hunter, J., Rivero-Arias, O., Angelov, A., Kim, E., Fotheringham, I., & Leal, J. (2014). Epidemiology of fragile X syndrome: a systematic review and meta-analysis. American Journal of Medical Genetics Part A, 164(7), 1648–1658. doi: 10.1002/ajmg.a.36511.CrossRefGoogle Scholar
  11. Jang, J.-H. H., Lee, K., Cho, E.-H. H., Lee, E.-H. H., Kim, J.-W. W., & Ki, C.-S. S. (2014). Frequency of FMR1 premutation carriers and rate of expansion to full mutation in a retrospective diagnostic FMR1 Korean sample. Clinical Genetics, 85(1), 441–445. doi: 10.1111/cge.12195.CrossRefPubMedGoogle Scholar
  12. Kuppermann, M., Nakagawa, S., Cohen, S. R., Dominguez-Pareto, I., Shaffer, B. L., & Holloway, S. D. (2011). Attitudes toward prenatal testing and pregnancy termination among a diverse population of parents of children with intellectual disabilities. Prenatal Diagnosis, 31(13), 1251–1258. doi: 10.1002/pd.2880.CrossRefPubMedGoogle Scholar
  13. Lyon, E., Laver, T., Yu, P., Jama, M., Young, K., Zoccoli, M., et al. (2010). A simple, high-throughput assay for Fragile X expanded alleles using triple repeat primed PCR and capillary electrophoresis. The Journal of Molecular Diagnostics : JMD, 12(4), 505–511. doi: 10.2353/jmoldx.2010.090229.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Metcalfe, S. A. (2012). Carrier screening in preconception consultation in primary care. Journal of Community Genetics, 3(3), 193–203. doi: 10.1007/s12687-011-0071-z.CrossRefPubMedGoogle Scholar
  15. Musci, T. J., Caughey, A. B., Smith, W., Schwartz, M., & Sampson, J. (2005). Cost-effectiveness analysis of prenatal population-based fragile X carrier screening. American Journal of Obstetrics and Gynecology, 192, 1905–1915. doi: 10.1016/j.ajog.2005.02.052.CrossRefPubMedGoogle Scholar
  16. Newcombe, R. G. (1998). Two-sided confidence intervals for the single proportion: comparison of seven methods. Statistics in Medicine, 17(8), 857–872.CrossRefPubMedGoogle Scholar
  17. Nolin, S. L., Sah, S., Glicksman, A., Sherman, S. L., Allen, E., Berry-Kravis, E., et al. (2013). Fragile X AGG analysis provides new risk predictions for 45–69 repeat alleles. American Journal of Medical Genetics Part A, 161(4), 771–778. doi: 10.1002/ajmg.a.35833.CrossRefGoogle Scholar
  18. Seltzer, M. M., Baker, M. W., Hong, J., Maenner, M., Greenberg, J., & Mandel, D. (2012). Prevalence of CGG expansions of the FMR1 gene in a US population-based sample. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication of the International Society of Psychiatric Genetics, 159B(5), 589–597. doi: 10.1002/ajmg.b.32065.CrossRefGoogle Scholar
  19. Tassone, F., Iong, K. P., Tong, T.-H., Lo, J., Gane, L. W., Berry-Kravis, E., et al. (2012). FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States. Genome Medicine, 4(12), 100. doi: 10.1186/gm401.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Toledano-Alhadef, H., Basel-Vanagaite, L., Magal, N., Davidov, B., Ehrlich, S., Drasinover, V., et al. (2001). Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. The American Journal of Human Genetics, 69, 351–360.CrossRefPubMedGoogle Scholar
  21. Yrigollen, C. M., Durbin-Johnson, B., Gane, L., Nelson, D. L., Hagerman, R., Hagerman, P. J., & Tassone, F. (2012). AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genetics in Medicine, 14, 729–736. doi: 10.1038/gim.2012.34.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2016

Authors and Affiliations

  • Ramona Alfaro Arenas
    • 1
    • 2
  • Jordi Rosell Andreo
    • 1
    • 3
    • 4
  • Damián Heine Suñer
    • 1
    • 2
    • 3
    • 4
  • Group for the study of FXS in the Balearic Islands
  1. 1.Sección Genética Hospital Universitario Son EspasesPalma de MallorcaSpain
  2. 2.Institut d’Investigacions Sanitaries de Palma (Idispa)Palma de MallorcaSpain
  3. 3.Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)Palma de MallorcaSpain
  4. 4.Department of GeneticsHospital Universitario Son EspasesMallorcaSpain

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