Journal of Autism and Developmental Disorders

, Volume 46, Issue 6, pp 2088–2099 | Cite as

Infant Development in Fragile X Syndrome: Cross-Syndrome Comparisons

  • Jane E. RobertsEmail author
  • Lindsay M. McCary
  • Svetlana V. Shinkareva
  • Donald B. BaileyJr.
Original Paper


This study examined the developmental profile of male infants with fragile X syndrome (FXS) and its divergence from typical development and development of infants at high risk for autism associated with familial recurrence (ASIBs). Participants included 174 boys ranging in age from 5 to 28 months. Cross-sectional profiles on the Mullen Scales of Early Learning indicated infants with FXS could be differentiated from typically developing infants and ASIBs by 6 months of age. Infants with FXS displayed a trend of lower developmental skills with increasing age that was unique from the typically developing and ASIB groups. Findings suggest infants with FXS present with more significant, pervasive and early emerging delays than previously reported with potentially etiologically distinct developmental profiles.


Fragile X syndrome Autism Early development Infants Mullen 



Research was supported by funding from the Office of Special Education Programs, US Department of Education; H324C990042 (PI: Bailey) and the National Institute of Mental Health; R01MH0901194-01A1 (PI: Roberts). Data and research tools used in the preparation of this article reside in and were analyzed using the NIH-supported NIMH Data Repositories, a collaborative informatics system created by the National Institutes of Health to provide a national resource to support and accelerate research in mental health related conditions.

Author Contributions

Dr. Roberts assisted with the conceptualization of the study, extensively revised the manuscript, and approved final manuscript as submitted. Dr. McCary assisted with the conceptualization of the study, wrote the initial draft of the manuscript, reviewed and revised the manuscript, and assisted with statistical analysis. Dr. Shinkareva provided expertise on the data analysis, assisted in writing the results, and approved final manuscript. Dr. Bailey provided expertise in the conceptualization of the manuscript, reviewed and revised the manuscript, and approved final submission.


  1. Bailey, D. B, Jr, Hatton, D. D., Mesibov, G., Ament, N., & Skinner, M. (2000). Early development, temperament, and functional impairment in autism and fragile X syndrome. Journal of Autism and Developmental Disorders, 30, 557–567.CrossRefGoogle Scholar
  2. Bailey, D. B, Jr, Hatton, D. D., & Skinner, M. (1998). Early developmental trajectories of males with fragile X syndrome. American Journal on Mental Retardation, 103(1), 29–39.CrossRefPubMedGoogle Scholar
  3. Bailey, D.B., Jr., Raspa, M., Bishop, E., & Holiday, D. (2009). No change in the age of diagnosis for FXS: Findings from a national parent survey. Pediatrics, 124(2), 527–533.CrossRefPubMedGoogle Scholar
  4. Bailey, D. B., Raspa, M., Olmsted, M., & Holiday, D. B. (2008). Co-occurring conditions associated with FMR1 gene variations: Findings from a national parent survey. American Journal of Medical Genetics Part A, 146(16), 2060–2069.CrossRefGoogle Scholar
  5. Bayley, N. (1993). Bayley scales of infant development: Manual. San Antonio, TX: Psychological Corporation.Google Scholar
  6. Bhat, A. N., Galloway, J. C., & Landa, R. J. (2012). Relation between early motor delay and later communication delay in infants at risk for autism. Infant Behavioral Development, 35(4), 838–846. doi: 10.1016/j.infbeh.2012.07.019.CrossRefGoogle Scholar
  7. Bryson, S., Zwaigenbaum, L., McDermott, C., Romboug, V., & Brian, J. (2008). The Autism Observation Scale for Infants: scale development and reliability data. Journal of Autism and Developmental Disorders, 38(4), 731–738.CrossRefPubMedGoogle Scholar
  8. Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J., Greenson, J., et al. (2010). Randomized, controlled trial of an intervention for toddlers with autism: The Early Start Denver Model. Pediatrics, 125(1), e17–e23.CrossRefPubMedGoogle Scholar
  9. Esposito, G., & Pasca, S. P. (2013). Motor abnormalities as a putative endophenotype for autism spectrum disorders. Frontiers in Integrative Neuroscience, 7, 43. doi: 10.3389/fnint.2013.00043.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Freund, L. S., Peebles, C. D., Aylward, E., & Reiss, A. L. (1995). Preliminary report on cognitive and adaptive behaviors of preschool-aged males with fragile X. Developmental Brain Dysfunction, 8, 242–251.Google Scholar
  11. Hagerman, R. J., Hull, C. E., Safanda, J. F., Carpenter, I., Staley, L. W., O’Connor, R. A., 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(4), 298–308.CrossRefPubMedGoogle Scholar
  12. Hagerman, R. J., Rivera, S. M., & Hagerman, P. J. (2008). The fragile X family of disorders: A model for autism and targeted treatments. Current Pediatric Reviews, 4, 40–52.CrossRefGoogle Scholar
  13. Hall, S. S., Lightbody, A. A., & Reiss, A. L. (2008). Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome. American Journal on Mental Retardation, 113(1), 44–53.CrossRefPubMedGoogle Scholar
  14. Harris, S. W., Hessl, D., Goodlin-Jones, B., Ferranti, J., Bacalman, S., Barbato, I., et al. (2008). Autism profiles of males with fragile X syndrome. American Journal on Mental Retardation, 113(6), 427–438.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hayes, A. F., & Matthes, J. (2009). Computational procedures for probing interactions in OLS and logistic regression: SPSS and SAS implementations. Behavior Research Methods, 41, 924–936.CrossRefPubMedGoogle Scholar
  16. Hazlett, H. C., Poe, M. D., Lightbody, A. A., Styner, M., MacFall, J. R., Reiss, A. L., & Piven, J. (2012). Trajectories of early brain volume development in fragile X syndrome and autism. Journal of the American Academy of Child and Adolescent Psychiatry, 51(9), 921–933.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Johnson, P. O., & Fay, L. C. (1950). The Johnson–Neyman technique, its theory and application. Psychometrika, 15(4), 349–367.CrossRefPubMedGoogle Scholar
  18. Jones, E. J., Gliga, T., Bedford, R., Charman, T., & Johnson, M. H. (2014). Developmental pathways to autism: A review of prospective studies of infants at risk. Neuroscience and Biobehavioral Reviews, 39, 1–33.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kaufmann, W. E., Cortell, R., Kau, A., Bukelis, I., Tierney, E., Gray, R., et al. (2004). Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. American Journal of Medical Genetics Part A, 129A, 225–234.CrossRefPubMedGoogle Scholar
  20. Klusek, J., Martin, G., & Losh, M. (2014). Consistency between research and clinical diagnoses of autism in boys and girls with fragile X syndrome. Journal of Intellectual Disability Research, 58(10), 940–952.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Lachiewicz, A. M., Gullion, C. M., Spiridigliozzi, G. A., & Aylsworth, A. S. (1987). Declining IQs of young males with the fragile X syndrome. American Journal of Mental Retardation, 92(3), 272–280.PubMedGoogle Scholar
  22. Landa, R., & Garrett-Mayer, E. (2006). Development in infants with autism spectrum disorders: a prospective study. Journal of Child Psychology and Psychiatry, 47(6), 629–638.CrossRefPubMedGoogle Scholar
  23. Landa, R., Gross, A. L., Stuart, E. A., & Bauman, M. (2012). Latent class analysis of early developmental trajectory in baby siblings of children with autism. Journal of Child Psychology and Psychiatry, 53(9), 986–996.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Landa, R., Gross, A. L., Stuart, E. A., & Faherty, A. (2013). Developmental trajectories in children with and without autism spectrum disorders: The first 3 years. Child Development, 84(2), 429–442. doi: 10.1111/j.1467-8624.2012.01870.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Matthews, N. L., Goldberg, W. A., & Lukowski, A. F. (2013). Theory of mind in children with autism spectrum disorder: Do siblings matter? Autism Research, 6(5), 443–453.CrossRefPubMedGoogle Scholar
  26. Mirrett, P. L., Bailey, D. B, Jr, Roberts, J. E., & Hatton, D. D. (2004). Developmental screening and detection of developmental delays in infants and toddlers with fragile X syndrome. Journal of Developmental and Behavioral Pediatrics, 25(1), 21–27.CrossRefPubMedGoogle Scholar
  27. Mitchell, S., Cardy, J. O., & Zwaigenbaum, L. (2011). Differentiating autism spectrum disorder from other developmental delays in the first two years of life. Developmental Disabilities Research Reviews, 17(2), 130–140.CrossRefPubMedGoogle Scholar
  28. Mullen, E. (1995). Mullen scales of early learning. Circle Pines, MN: American Guidance Service.Google Scholar
  29. Newborg, J., Stock, J. R., Wnek, L., Guidubaldi, J., & Svinicki, J. (1984). The Battelle developmental inventory. Allen, TX: DLM/Teaching Resources.Google Scholar
  30. Rice, C. E., Baio, J., Van Naarden, B. K., Doernberg, N., Meaney, F. J., & Kirby, R. S. (2007). A public health collaboration for the surveillance of autism spectrum disorders. Pediatric and Perinatal Epidemiology, 21(2), 179–190.CrossRefPubMedGoogle Scholar
  31. Rivard, M., Terroux, A., Mercier, C., & Parent-Boursier, C. (2015). Indicators of intellectual disabilities in young children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 45(1), 127–137.CrossRefPubMedGoogle Scholar
  32. Roberts, J. E., Hatton, D. D., Long, A. C. J., Anello, V., & Colombo, J. (2012a). Visual attention and autistic behavior in infants with fragile X syndrome. Journal of Autism and Developmental Disorders,. doi: 10.1007/s10803-011-1316-8.Google Scholar
  33. Roberts, J. E., Mankowski, J. B., Sideris, J., Goldman, B. D., Hatton, D. D., & Mirrett, P. L., et al. (2009). Trajectories and predictors of the development of very young boys with fragile X syndrome. Journal of Pediatric Psychology, 34(8), 1–10.Google Scholar
  34. Roberts, J. E., Tonnsen, B. L., McCary, L. M., Caravella, B. S., & Shinkareva, S. V. (under review). Autism symptoms in infants with fragile X syndrome.Google Scholar
  35. Roberts, J. E., Tonnsen, B. L., Robinson, A., & Shinkareva, S. V. (2012b). Heart activity and autistic behaviour in infants and toddlers with fragile X syndrome. American Journal of Intellectual and Developmental Disabilities, 117(2), 90–102. doi: 10.1352/1944-7558-117.2.90.CrossRefGoogle Scholar
  36. Rogers, S., Wehner, E., & Hagerman, R. (2001). The behavioral phenotype in fragile X: Symptoms of autism in very young children with FXS, idiopathic autism, and other developmental disorders. Journal of Developmental and Behavioral Pediatrics, 22, 409–417.CrossRefPubMedGoogle Scholar
  37. Sacrey, L. A., Bryson, S. E., & Zwaigenbaum, L. (2013). Prospective examination of visual attention during play in infants at high-risk for autism spectrum disorder: A longitudinal study from 6-36 months of age. Behavioral Brain Research, 256, 441–450. doi: 10.1016/j.bbr.2013.08.028.CrossRefGoogle Scholar
  38. Schopler, E., Reichler, R. J., & Renner, B. R. (1988). The Childhood Autism Rating Scale (CARS). Los Angeles: Western Psychological Services.Google Scholar
  39. Shen, M. D., Nordahl, C. W., Young, G. S., Wootton-Gorges, S. L., Lee, A., Liston, S. E., et al. (2013). Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder. Brain, 136(Pt 9), 2825–2835. doi: 10.1093/brain/awt166.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Vivanti, G., Barbaro, J., Hudry, K., Dissanayake, C., & Prior, M. (2013). Intellectual development in autism spectrum disorders: New insights from longitudinal studies. Frontiers in Human Neuroscience7, 354. doi: 10.3389/fnhum.2013.00354.
  41. Wolff, J. J., Gu, H., Gerig, G., Elison, J. T., Styner, M., Gouttard, S., et al. (2012). Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. American Journal of Psychiatry, 169(6), 589–600. doi: 10.1176/appi.ajp.2011.11091447.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Zingerevich, C., Greiss-Hess, L., Lemons-Chitwood, K., Harris, S. W., Hessl, D., Cook, K., et al. (2009). Motor abilities of children diagnosed with fragile X syndrome with and without autism. Journal of Intellectual Disability Research, 53(1), 11–18. doi: 10.1111/j.1365-2788.2008.01107.x.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Zwaigenbaum, L., Bryson, S., Rogers, T., Roberts, W., Brian, J., & Szatmari, P. (2005). Behavioral manifestations of autism in the first year of life. International Journal of Neuroscience, 23, 143–152.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jane E. Roberts
    • 1
    Email author
  • Lindsay M. McCary
    • 1
    • 2
  • Svetlana V. Shinkareva
    • 1
  • Donald B. BaileyJr.
    • 3
  1. 1.Department of PsychologyThe University of South CarolinaColumbiaUSA
  2. 2.Waisman CenterUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.RTI InternationalResearch Triangle ParkUSA

Personalised recommendations