Autism Spectrum Disorder Symptoms in Infants with Fragile X Syndrome: A Prospective Case Series
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No studies to date have prospectively examined early autism spectrum disorder (ASD) markers in infants with fragile X syndrome (FXS), who are at elevated risk for ASD. This paper describes the developmental profiles of eight infants with FXS from 9 to 24 months of age. Four meet diagnostic criteria for ASD at 24 months of age, and four do not. Trends in these case studies suggest that early social-communicative deficits differentiate infants with and without later ASD diagnoses in ways that are similar to later-born siblings of children with ASD. Repetitive behaviors and cognitive and adaptive impairments are present in all FXS infants throughout development, suggesting that these deficits reflect the general FXS phenotype and not ASD in FXS specifically.
KeywordsFragile X syndrome Autism spectrum disorder Infants Case studies
The authors are grateful to the families who participated in this research. Special thanks to John Colombo for his thoughtful feedback on an earlier draft of this manuscript. This research was funded by the National Institute of Mental Health (R01MH107573; R01MH090194; PI: Roberts).
AH participated in the design and coordination of the study, performed the statistical analyses, and drafted the manuscript; KC compiled data and drafted the case summaries; LR and JE assisted with drafting the manuscript; KH led the clinical diagnostic procedures and contributed to the case summaries. JR conceived of the study and assisted with drafting the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Research involving animal and human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- Bedford, R., Elsabbagh, M., Gliga, T., Pickles, A., Senju, A., Charman, T., et al. (2012). Precursors to social and communication difficulties in infants at-risk for autism: Gaze following and attentional engagement. Journal of Autism and Developmental Disorders, 42(10), 2208–2218. doi: 10.1007/s10803-012-1450-y.CrossRefPubMedGoogle Scholar
- Budimirovic, D. B., Bukelis, I., Cox, C., Gray, R. M., Tierney, E., & Kaufmann, W. E. (2006). Autism spectrum disorder in fragile X syndrome: Differential contribution of adaptive socialization and social withdrawal. American Journal of Medical Genetics Part A, 140A, 1814–1826.CrossRefPubMedGoogle Scholar
- CDC. (2014). Prevalence of autism spectrum disorder among children aged 8 years: Autism and developmental disabilities monitoring network, 11 sites, United States, 2010. Morbidity and Mortality Weekly Report Surveillance Summaries, 64(SS02), 1–21.Google Scholar
- Christensen, L., Hutman, T., Rozga, A., Young, G. S., Ozonoff, S., Rogers, S. J., et al. (2010). Play and developmental outcomes in infant siblings of children with autism. Journal of Autism and Developmental Disorders, 40(8), 946–957. doi: 10.1007/s10803-010-0941-y.CrossRefPubMedPubMedCentralGoogle Scholar
- Clifford, S. M., Hudry, K., Elsabbagh, M., Charman, T., Johnson, M. H., et al. (2013). Temperament in the first 2 years of life in infants at high-risk for autism spectrum disorders. Journal of Autism and Developmental Disorders, 43(3), 673–686. doi: 10.1007/s10803-012-1612-y.CrossRefPubMedGoogle Scholar
- Damiano, C. R., Nahmias, A., Hogan-Brown, A. L., & Stone, W. L. (2013). What do repetitive and stereotyped movements mean for infant siblings of children with autism spectrum disorders? Journal of Autism and Developmental Disorders, 43(6), 1326–1335. doi: 10.1007/s10803-012-1681-y.CrossRefPubMedPubMedCentralGoogle Scholar
- Estes, A., Zwaigenbaum, L., Gu, H. B., St John, T., Paterson, S., Elison, J, T., et al. (2015). Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life. Journal of Neurodevelopmental Disorders, 7, 10. doi: 10.1186/s11689-015-9117-6.CrossRefGoogle Scholar
- Fernandez-Carvajal, I., Walichiewicz, P., Xiaosen, X., Pan, R., Hagerman, P. J., & Tassone, F. (2009). Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population. Journal of Molecular Diagnostics, 11(4), 324–329.CrossRefPubMedPubMedCentralGoogle Scholar
- Filliter, J. H., Longard, J., Lawrence, M. A., Zwaigenbaum, L., Brian, J., Garon, N., et al. (2015). Positive affect in infant siblings of children diagnosed with autism spectrum disorder. Journal of Abnormal Child Psychology, 43(3), 567–575. doi: 10.1007/s10802-014-9921-6.CrossRefPubMedGoogle Scholar
- Gammer, I., Bedford, R., Elsabbagh, M., Garwood, H., Pasco, G., Tucker, L., et al. (2015). Behavioural markers for autism in infancy: Scores on the Autism Observational Scale for Infants in a prospective study of at-risk siblings. Infant Behavior & Development, 38, 107–115. doi: 10.1016/j.infbeh.2014.12.017.CrossRefGoogle Scholar
- Jones, E. J. H., Venema, K., Earl, R., Lowy, R., Barnes, K., Estes, A., et al. (2016). Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: A longitudinal prospective study of infants at high familial risk. Journal of Neurodevelopmental Disorders, 8, 7. doi: 10.1186/s11689-016-9139-8.CrossRefPubMedPubMedCentralGoogle Scholar
- Kaufmann, W. E., Cortell, R., Kau, A. S., Bukelis, I., Tierney, E., Gray, R. M., et al. (2004). Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. American Journal of Medical Genetics Part A, 129A(3), 225–234. doi: 10.1002/ajmg.a.30229.CrossRefGoogle Scholar
- Lord, C., Rutter, M., DiLavore, P. C., Risi, S., Gotham, K., & Bishop, S. L. (2012). Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). Los Angeles, CA: Western Psychological Services.Google Scholar
- Mullen, E. M. (1995). Mullen Scales Of Early Learning. Circle Pines, MN: American Guidance Service.Google Scholar
- Roberts, J. E., Tonnsen, B. L., Robinson, A., & Shinkareva, S. V. (2012). Heart activity and autistic behavior in infants and toddlers with fragile X syndrome. American Journal on Intellectual and Developmental Disabilities, 117(2), 90–102. doi: 10.1352/1944-7558-117.2.90.CrossRefPubMedPubMedCentralGoogle Scholar
- Rogers, S. J., Wehner, D. E., & Hagerman, R. (2001). The behavioral phenotype in fragile X: Symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. Journal of Developmental Behavioral Pediatrics, 22(6), 409–417.CrossRefPubMedGoogle Scholar
- Sacrey, L. A. R., 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 to 36 months of age. Behavioural Brain Research, 256, 441–450. doi: 10.1016/j.bbr.2013.08.028.CrossRefPubMedGoogle Scholar
- Sparrow S. S., Balla D. A., & Cicchetti D. V. (1984). Vineland Adaptive Behavior Scales. Circle Pines, MN: American Guidance Service.Google Scholar
- Sparrow, S. S., Cicchetti, D. V., & Balla, D. A. (2005). Vineland Adaptive Behavior Scales—Second Edition. Circle Pines, MN: American Guidance Service.Google Scholar
- Thurman, A. J., McDuffie, A., Kover, S. T., Hagerman, R. J., & Abbeduto, L. (2015). Autism symptomatology in boys with fragile X syndrome: A cross-sectional developmental trajectories comparison with nonsyndromic autism spectrum disorder. Journal of Autism and Developmental Disorders, 45(9), 2816–2832. doi: 10.1007/s10803-015-2443-4..CrossRefPubMedPubMedCentralGoogle Scholar