ASD Comorbidity in Fragile X Syndrome: Symptom Profile and Predictors of Symptom Severity in Adolescent and Young Adult Males

Abstract

Many males with FXS meet criteria for ASD. This study was designed to (1) describe ASD symptoms in adolescent and young adult males with FXS (n = 44) and (2) evaluate the contributions to ASD severity of cognitive, language, and psychiatric factors, as well as FMRP (the protein deficient in FXS). A few ASD symptoms on the ADOS-2 were universal in the sample. There was less impairment in restricted and repetitive behaviors (RRB) than in the social affective (SA) domain. The best predictor of overall ASD severity and SA severity was expressive syntactic ability. RRB severity was best predicted by the psychiatric factors. Implications for clinical practice and for understanding the ASD comorbidity in FXS are discussed.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Abbeduto, L., Brady, N., & Kover, S. T. (2007). Language development and fragile X syndrome: Profiles, syndrome-specificity, and within-syndrome differences. Mental Retardation and Developmental Disabilities Research Reviews, 13, 36–46.

    PubMed  Google Scholar 

  2. Abbeduto, L., McDuffie, A., & Thurman, A. J. (2014). The fragile X syndrome-autism comorbidity: What do we really know? Frontiers in Genetics, 5, 355.

    PubMed  PubMed Central  Google Scholar 

  3. Abbeduto, L., Murphy, M., Cawthon, S., Richmond, E., Weissman, M., Karadottir, S., et al. (2003). Receptive language skills of adolescents and young adults with mental retardation: A comparison of DS and fragile X syndrome. American Journal on Mental Retardation, 108, 149–160.

    PubMed  Google Scholar 

  4. Abbeduto, L., Short-Meyerson, K., Benson, G., & Dolish, J. (2004). Relation between theory of mind and language ability in children and adolescents with mental retardation. Journal of Intellectual Disability Research, 48, 150–159.

    PubMed  Google Scholar 

  5. Adayev, T., LaFauci, G., Dobkin, C., Caggana, M., Wiley, V., Field, M., et al. (2014). Fragile X 8 protein in newborn dried blood spots. BMC Medical Genetics, 15(1), 119.

    PubMed  PubMed Central  Google Scholar 

  6. Bailey, D. B., Hatton, D. D., Mesibov, G. B., 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.

    Google Scholar 

  7. Bailey, D. B., Jr., Hatton, D. D., Skinner, M., & Mesibov, G. (2001). Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. Journal of Autism and Developmental Disorders, 31(2), 165–174.

    PubMed  Google Scholar 

  8. Bailey, D. B., Jr., 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 Medication Genetics A, 146(16), 2060–2069.

    Google Scholar 

  9. Bassell, G. J., & Warren, S. T. (2008). Fragile X syndrome: Loss of local mRNA regulation alters synaptic development and function. Neuron, 60, 201–214.

    PubMed  PubMed Central  Google Scholar 

  10. Belser, R., & Sudhalter, V. (1995). Arousal difficulties in males with fragile X syndrome: A preliminary report. Developmental Brain Dysfunction, 8, 270–279.

    Google Scholar 

  11. Belser, R., & Sudhalter, V. (2001). Conversational characteristics of children with fragile X syndrome: Repetitive speech. American Journal on Mental Retardation, 106, 28–38.

    PubMed  Google Scholar 

  12. Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society, Series B (Methodological), 57(1), 289–300.

    Google Scholar 

  13. Benson, G., Abbeduto, L., Short, K., Nuccio, J. B., & Maas, F. (1993). Development of a theory of mind in persons with mental retardation. American Journal on Mental Retardation, 98, 427–433.

    PubMed  Google Scholar 

  14. Boucher, J. (2003). Language development in autism. International Journal of Pediatric Otorhinolaryngology, 67(Suppl 1), S159–S163.

    PubMed  Google Scholar 

  15. Budimirovic, D. B., & Kaufmann, W. E. (2011). What can we learn about autism from studying fragile X syndrome? Developmental Neuroscience, 33, 379–394.

    PubMed  PubMed Central  Google Scholar 

  16. Bullard, L., McDuffie, A., & Abbeduto, L. (2017). Distance delivery of a parent-implemented language intervention for young boys with fragile X syndrome. Autism & Developmental Language Impairments, 2, 1–22.

    Google Scholar 

  17. Caravella, K. E., & Roberts, J. E. (2017). Adaptive skill trajectories in infants with fragile X syndrome contrasted to typical controls and infants at high risk for autism. Research in Autism Spectrum Disorders, 40, 1–12.

    PubMed  PubMed Central  Google Scholar 

  18. Carrow-Woolfolk, E. (1999). Comprehensive assessment of spoken language. Circle Pines: American Guidance Service.

    Google Scholar 

  19. Clifford, S., Dissanyake, C., Bui, Q. M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2007). Autism spectrum phenotype in males and females with fragile X full mutation and permutation. Journal of Autism and Developmental Disorders, 37, 738–747.

    PubMed  Google Scholar 

  20. Cordeiro, L., Ballinger, E., Hagerman, R., & Hessl, D. (2011). Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: Prevalence and characterization. Journal of Neurodevelopmental Disorders, 3, 57–67.

    PubMed  Google Scholar 

  21. Cornish, K., Sudhalter, V., & Turk, J. (2004). Attention and language in fragile X. Mental Retardation and Developmental Disabilities Research Reviews, 10(1), 11–16.

    PubMed  Google Scholar 

  22. Crawford, D. C., Acuña, J. M., & Sherman, S. L. (2001). FMR1 and the fragile X syndrome: Human genome epidemiology review. Genetics in Medicine, 3, 359–371.

    PubMed  PubMed Central  Google Scholar 

  23. Demark, J. L., Feldman, M. A., & Holden, J. J. (2003). Behavioral relationship between autism and fragile X syndrome. American Journal on Mental Retardation, 108, 314–326.

    PubMed  Google Scholar 

  24. Ellis Weismer, S., Lord, C., & Esler, A. (2010). Early language patterns of toddlers on the autism spectrum compared to toddlers with developmental delay. Journal of Autism and Developmental Disorders, 40(10), 1259–1273.

    PubMed  Google Scholar 

  25. Esbensen, A. J., Rojahn, J., Aman, M. G., & Ruedrich, S. (2003). Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. Journal of Autism and Developmental Disorders, 33, 617–629.

    PubMed  Google Scholar 

  26. Estigarribia, B., Roberts, J. E., Sideris, J., & Price, J. (2011). Expressive morphosyntax in boys with fragile X syndrome with and without autism spectrum disorder. International Journal of Language & Communication Disorders, 46, 216–230.

    Google Scholar 

  27. Ezell, J., et al. (in press). Prevalence and predictors of anxiety disorders in adolescent and adult males with autism spectrum disorder and fragile X syndrome. Journal of Autism and Developmental Disorders.

  28. Finestack, L. H., & Abbeduto, L. (2010). Expressive language profiles of verbally expressive adolescents and young adults with Down syndrome or fragile X syndrome. Journal of Speech, Language, and Hearing Research, 53, 1334–1348.

    PubMed  PubMed Central  Google Scholar 

  29. Fisch, G. S., Carpenter, N., Howard-Peebles, P. N., Holden, J. J., Tarleton, J., & Simensen, R. (2010). The course of cognitive-behavioral development in children with the FMR1 mutation, Williams-Beuren syndrome, and neurofibromatosis type 1: The effect of gender. American Journal of Medical Genetics, 152(6), 1498–1509.

    Google Scholar 

  30. Gabriels, R. L., Cuccaro, M. L., Hill, D. E., Ivers, B. J., & Goldson, E. (2005). Repetitive behaviors in autism: Relationships with associated clinical features. Research in Developmental Disabilities, 26, 169–181.

    PubMed  Google Scholar 

  31. Hagerman, R. (1999). Neurodevelopmental disorders. Oxford: Oxford University Press.

    Google Scholar 

  32. Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B. Jr., Moine, H., Kooy, R. F., et al. (2017). Fragile X syndrome. Nature Reviews Disease Primers, 3, 17065.

    PubMed  Google Scholar 

  33. Harris, S. W., Goodlin-Jones, B., Nowicki, S., Bacalman, S., Tassone, F., & Hagerman, R. J. (2005). Autism profiles of young males with fragile X syndrome. Journal of Developmental and Behavioral Pediatrics, 26(6), 464.

    Google Scholar 

  34. 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, 427–438.

    PubMed  Google Scholar 

  35. Hatton, D. D., Sideris, J., Skinner, M., Mankowski, J., Bailey, D. B., Roberts, J., et al. (2006). Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP. American Journal of Medical Genetics, 140(17), 1804–1813.

    Google Scholar 

  36. Hazlett, H. C., Poe, M. D., Lightbody, A. A., Gerig, G., Macfall, J. R., & Ross, A. K. (2009). Teasing apart the heterogeneity of autism: Same behavior, different brains in toddlers with fragile X syndrome and autism. Journal of Neurodevelopmental Disorders, 1, 81–90.

    PubMed  PubMed Central  Google Scholar 

  37. Hernandez, R. N., Feinberg, R. L., Vaurio, R., Passanante, N. M., Thompson, R. E., & Kaufmann, W. E. (2009). Autism spectrum disorder in fragile X syndrome: A longitudinal evaluation. American Journal of Medical Genetics, 149(6), 1125–1137.

    Google Scholar 

  38. Hessl, D., Nguyen, D., Green, C., Chavez, A., Tassone, F., Hagerman, R., et al. (2009). A solution to limitations of cognitive testing in children with intellectual disabilities: The case of fragile X syndrome. Journal of Neurodevelopmental Disorders, 1, 33–45.

    PubMed  Google Scholar 

  39. Hus, V., Gotham, K., & Lord, C. (2014). Standardizing ADOS domain scores: Separating severity of social affect and restricted and repetitive behaviors. Journal of Autism and Developmental Disorders, 44(10), 2400–2412.

    PubMed  PubMed Central  Google Scholar 

  40. Kau, A., Tierney, E., Bukelis, I., Stump, M., Kates, W., Trescher, W., et al. (2004). Social behavior profile in young males with fragile X syndrome: Characteristics and specificity. American Journal of Medical Genetics, 126, 9–17.

    Google Scholar 

  41. Kaufmann, W., Cortell, R., Kau, A., Bukelis, I., Tierney, E., Gray, R., et al. (2004). Autism spectrum disorder in fragile X syndrome. American Journal of Medical Genetics, 129, 225–234.

    Google Scholar 

  42. Kaufmann, W. E., Capone, G., Clarke, M., & Budimirovic, D. B. (2008). Autism in genetic intellectual disability: Insights into idiopathic autism. In A. W. Zimmerman (Ed.), Current theories and evidence (pp. 81–108). Totowa: The Humana Press Inc.

    Google Scholar 

  43. Kaufmann, W. E., Kidd, S. A., Andrews, H. F., Budimirovic, D. B., Esler, A., Haas-Givler, B., et al. (2017). Autism spectrum disorder in fragile X syndrome: Cooccurring conditions and current treatment. Pediatrics, 139(Suppl 3), S194–S206.

    PubMed  PubMed Central  Google Scholar 

  44. Kjelgaard, M., & Tager-Flusberg, H. (2001). An investigation of language impairment in autism: Implications for genetic subgroups. Language and Cognitive Processes, 16(2–3), 287–308.

    PubMed  PubMed Central  Google Scholar 

  45. Klusek, J., Martin, G. E., & Losh, M. (2014a). Consistency between research and clinical diagnoses of autism among boys and girls with fragile X syndrome. Journal of Intellectual Disabilities Research, 58, 940–952.

    Google Scholar 

  46. Klusek, J., Martin, G. E., & Losh, M. (2014b). A comparison of pragmatic language in boys with autism and fragile X syndrome. Journal of Speech, Language and Hearing Research, 57, 1692–1707.

    Google Scholar 

  47. Kover, S. T., & Abbeduto, L. (2010). Expressive language in male adolescents with fragile X syndrome with and without comorbid autism. Journal of Intellectual Disability Research, 54, 246–265.

    PubMed  Google Scholar 

  48. Kover, S. T., McDuffie, A., Abbeduto, L., & Brown, W. T. (2012). Effects of sampling context on spontaneous expressive language in males with fragile X syndrome or down syndrome. Journal of Speech, Language, and Hearing Research, 55(4), 1022–1038.

    PubMed  PubMed Central  Google Scholar 

  49. Kover, S. T., Pierpont, E., Kim, J.-S., Brown, W. E., & Abbeduto, L. (2013). A neurodevelopmental perspective on the acquisition of nonverbal cognitive skills in adolescents with fragile X syndrome. Developmental Neuropsychology, 38, 445–460.

    PubMed  Google Scholar 

  50. LaFauci, G., Adayev, T., Kascsak, R., Kascsak, R., Nolin, S., Mehta, P., et al (2013). Fragile X screening by quantification of FMRP in dried blood spots by a Luminex immunoassay. Journal of Molecular Diagnostics, 15(4), 508–517.

    PubMed  Google Scholar 

  51. Lee, M., Bush, L., Martin, G., Barstein, J., Heckel, N., Klusek, J., et al. (2017). A multi-method investigation of pragmatic development in Down syndrome. American Journal of Intellectual and Developmental Disabilities, 122, 289–309.

    Google Scholar 

  52. Lee, M., Martin, G. E., Berry-Kravis, E., & Losh, M. (2016). A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome. Journal of Neurodevelopmental Disorders, 8, 47.

    PubMed  PubMed Central  Google Scholar 

  53. Lewis, P., Abbeduto, L., Murphy, M., Richmond, E., Giles, N., Bruno, L., et al. (2006). Cognitive language and social-cognitive skills of individuals with fragile X syndrome with and without autism. Journal of Intellectual Disability Research, 50, 532–545.

    PubMed  Google Scholar 

  54. Ligsay, A., & Hagerman, R. J. (2016). Review of targeted treatments in fragile X syndrome. Intractable & Rare Diseases Research, 5(3), 158–167.

    Google Scholar 

  55. Loesch, D. Z., Bui, Q. M., Dissanayake, C., Clifford, S., Gould, E., Bulhak-Paterson, D., et al. (2007). Molecular and cognitive predictors of the continuum of autistic behaviours in fragile X. Neuroscience & Biobehavioral Reviews, 31, 315–326.

    Google Scholar 

  56. Loesch, D. Z., Huggins, R. M., & Hagerman, R. J. (2004). Phenotypic variation and FMRP levels in fragile X. Mental Retardation and Developmental Disabilities Research Reviews, 10, 31–41.

    PubMed  Google Scholar 

  57. Lord, C., Rutter, M., DeLavore, P., Risi, S., Gotham, K., & Bishop, S. L. (2012). Autism diagnostic observation schedule, second edition (ADOS-2) manual (part I): Modules 14. Torrance: Western Psychological Services.

    Google Scholar 

  58. Luyster, R. J., Kadlec, M. B., Carter, A., & Tager-Flusberg, H. (2008). Language assessment and development in toddlers with autism spectrum disorders. Journal of Autism and Developmental Disorders, 38(8), 1426–1438.

    PubMed  Google Scholar 

  59. Martin, G. E., Barstein, J., Hornickel, J., Matherly, S., Durante, G., & Losh, M. (2017). Signaling of noncomprehension in communication breakdowns in fragile X syndrome, Down syndrome, and autism spectrum disorder. Journal of Communication Disorders, 65, 22–34.

    PubMed  PubMed Central  Google Scholar 

  60. Martin, G. E., Losh, M., Estigarribia, B., Sideris, J., & Roberts, J. (2013). Longitudinal profiles of expressive vocabulary, syntax and pragmatic language in boys with fragile X syndrome or Down syndrome. International Journal of Language & Communicative Disorders, 48, 432–443.

    Google Scholar 

  61. Martin, G. E., Roberts, J. E., Helm-Estabrooks, N., Sideris, J., Vanderbilt, J., & Moskowitz, L. (2012). Perseveration in the connected speech of boys with fragile X syndrome with and without autism spectrum disorder. American Journal on Intellectual and Developmental Disabilities, 117(5), 384–399.

    PubMed  PubMed Central  Google Scholar 

  62. McDuffie, A., Abbeduto, L., Lewis, P., Kover, S., Kim, J., Weber, A., et al. (2010). Autism spectrum disorder in children and adolescents with fragile X syndrome: Within-syndrome differences and age-related changes. American Journal on Intellectual and Developmental Disabilities, 115(4), 307–326.

    PubMed  PubMed Central  Google Scholar 

  63. McDuffie, A., Banasik, A., Bullard, L., Nelson, S., Feigles, R. T., Hagerman, R. et al. (2018). Distance delivery of a spoken language intervention for school-aged and adolescent boys with fragile X syndrome. Developmental Neurorehabilitation, 21, 48–63.

    PubMed  Google Scholar 

  64. McDuffie, A., Kover, S. T., Abbeduto, L., Lewis, P., & Brown, W. T. (2012). Profiles of receptive and expressive language in males with comorbid fragile X syndrome and autism. American Journal on Intellectual and Developmental Disabilities, 117, 18–32.

    PubMed  PubMed Central  Google Scholar 

  65. McDuffie, A., Machalicek, W., Bullard, L., Nelson, S., Tempero-Feigles, R., Castignetti, N., et al. (2016). A spoken language intervention for school-aged boys with fragile X syndrome. American Journal on Intellectual and Developmental Disabilities, 121, 236–265.

    PubMed  PubMed Central  Google Scholar 

  66. McDuffie, A., Oakes, A., Machalicek, W., Ma, M., Bullard, L., Nelson, S., et al. (2016). Early language intervention using distance video-teleconferencing: A pilot study of young males with fragile X syndrome and their mothers. American Journal of Speech-Language Pathology, 25, 46–66.

    PubMed  Google Scholar 

  67. McDuffie, A., Thurman, A. J., Hagerman, R. J., & Abbeduto, L. (2015). Symptoms of autism in males with fragile X syndrome: A comparison to nonsyndromic ASD using current ADI-R scores. Journal of Autism and Developmental Disorders, 45, 1925–1937.

    PubMed  PubMed Central  Google Scholar 

  68. Merenstein, S. A., Sobesky, W. E., Taylor, A. K., Riddle, J. E., Tran, H. X., & Hagerman, R. J. (1996). Molecular-clinical correlations in males with an expanded FMR1 mutation. American Journal of Medical Genetics Part A, 64(2), 388–394.

    Google Scholar 

  69. Miguel, E. C., Baer, L., Coffey, B. J., Rauch, S. L., Savage, C. R., O’Sullivan, R. L., et al. (1997). Phenomenological differences appearing with repetitive behaviours in obsessive-compulsive disorder and Gilles de la Tourette’s syndrome. The British Journal of Psychiatry, 170(2), 140–145.

    PubMed  Google Scholar 

  70. Miller, M., Iosif, A. M., Young, G. S., Hill, M. M., & Ozonoff, S. (2018). Early detection of ADHD: Insights from infant siblings of children with autism. Journal of Clinical Child & Adolescent Psychology. https://doi.org/10.1080/15374416.2016.1220314

    Google Scholar 

  71. Mitchell, S., Brian, J., Zwaigenbaum, L., Roberts, W., Szatmari, P., Smith, I., et al. (2006). Early language and communication development of infants later diagnosed with autism spectrum disorder. Journal of Developmental and Behavioral Pediatrics, 27(2 Suppl), S69–S78.

    PubMed  Google Scholar 

  72. Müller, R. A., & Amaral, D. G. (2017). Editorial: Time to give up on autism spectrum disorder? Autism Research, 10(1), 10–14.

    PubMed  Google Scholar 

  73. Murphy, M. M., & Abbeduto, L. (2007). Gender differences in repetitive language in fragile X syndrome. Journal of Intellectual Disability Research, 51, 387–390.

    PubMed  Google Scholar 

  74. Niu, M., Han, Y., Dy, A. B. C., Du, J., Jin, H., Qin, J., et al. (2017). Autism symptoms in fragile X syndrome. Journal of Child Neurology, 32(10), 903–909.

    PubMed  Google Scholar 

  75. Oakes, A., Kover, S. T., & Abbeduto, L. (2013). Language comprehension profiles of young adolescents with fragile X syndrome. American Journal of Speech Language Pathology, 22, 615–626.

    PubMed  PubMed Central  Google Scholar 

  76. Oakes, A., McDuffie, A., Thurman, A. J., Bullard, L., & Abbeduto, L. (2016). Characterising repetitive behaviours in young males with fragile X syndrome. Journal of Intellectual Disability Research, 60, 54–67.

    PubMed  Google Scholar 

  77. Oostra, B. A., & Willemson, R. (2003). A fragile X balance: FMR1 expression levels. Human Molecular Genetics, 12, 249–457.

    Google Scholar 

  78. Park, C. J., Yelland, G. W., Taffe, J. R., & Gray, K. M. (2012). Morphological and syntactic skills in language samples of preschool aged children with autism: Atypical development? International Journal of Speech Language Pathology, 14, 95–108.

    PubMed  Google Scholar 

  79. Philofsky, A., Hepburn, S., Hayes, A., Rogers, S., & Hagerman, R. (2004). Linguistic and cognitive functioning and autism symptoms in young children with fragile X syndrome. American Journal on Mental Retardation, 109(3), 208–218.

    PubMed  Google Scholar 

  80. Price, J. R., Roberts, J. E., Hennon, E. A., Berni, M. C., Anderson, K. L., & Sideris, J. (2008). Syntactic complexity during conversation of boys with fragile X syndrome and down syndrome. Journal of Speech Language and Hearing Research, 51(1), 3–15.

    Google Scholar 

  81. Risi, S., Lord, C., Gotham, K., Corsello, C., Chrysler, C., Szatmari, P., et al. (2006). Combining information from multiple sources in the diagnosis of autism spectrum disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 45(9), 1094–1103.

    PubMed  Google Scholar 

  82. Roberts, J. E., Clarke, M. A., Alcorn, K., Carter, J. C., Long, A. C., & Kaufmann, W. E. (2009). Autistic behavior in boys with fragile X syndrome: Social approach and HPA-axis dysfunction. Journal of Neurodevelopmental Disorders, 1, 283–291.

    PubMed  PubMed Central  Google Scholar 

  83. Roberts, J. E., Ezell, J. E., Fairchild, A. J., Klusek, J., Thurman, A. J., McDuffie, A., et al. (2018). Biobehavioral composite of social aspects of anxiety in young adults with fragile X contrasted to autism spectrum disorder. American Journal of Medical Genetics Part B. https://doi.org/10.1002/ajmg.b.32674

    Google Scholar 

  84. Roberts, J. E., Martin, G., Moskowitz, L., Harris, A. A., Foreman, J., Nelson, L. (2007). Discourse skills of boys with fragile X syndrome in comparison to boys with Down syndrome. Journal of Speech, Language, and Hearing Research, 50, 475–492.

    PubMed  Google Scholar 

  85. Roberts, J. E., Tonnsen, B., 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.

    PubMed  PubMed Central  Google Scholar 

  86. Roberts, J. E., Weisenfeld, L. A., Hatton, D. D., Heath, M., & Kaufmann, W. E. (2007). Social approach and autistic behavior in children with fragile X syndrome. Journal of Autism and Developmental Disorders, 37, 1748–1760.

    PubMed  Google Scholar 

  87. Rogers, S., Wehner, 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 and Behavioral Pediatrics, 22, 409–418.

    PubMed  Google Scholar 

  88. Roid, G., & Miller, L. (1997). Leiter international performance scale-revised. Wood Dale: Stoelting.

    Google Scholar 

  89. Rutter, M., LeCouteur, A., & Lord, C. (2008). Autism diagnostic interview-revised. Los Angeles: Western Psychological Services.

    Google Scholar 

  90. Scherr, J. F., Hahn, L. J., Hooper, S. R., Hatton, D., & Roberts, J. E. (2016). HPA axis function predicts development of working memory in boys with FXS. Brain and Cognition, 102, 80–90.

    PubMed  PubMed Central  Google Scholar 

  91. Shield, A., Pyers, J., Martin, A., & Tager-Flusberg, H. (2016). Relations between language and cognition in native-signing children with autism spectrum disorder. Autism Research, 9(12), 1304–1315.

    PubMed  Google Scholar 

  92. Simonoff, E., Pickles, A., Charman, T., Chandler, S., Loucas, T., & Baird, G. (2008). Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample. Journal of American Academy Child and Adolescent Psychiatry, 47, 921–929.

    Google Scholar 

  93. Skinner, M., Hooper, S., Hatton, D., Roberts, J., Mirrett, P., Schaaf, J., et al. (2005). Mapping nonverbal IQ in young boys with fragile X syndrome. American Journal of Medical Genetics A, 132, 25–32.

    Google Scholar 

  94. Stembalska, A., Łaczmańska, I., Gil, J., & Pesz, K. A. (2016). Fragile X syndrome in females–a familial case report and review of the literature. Developmental Period Medicine, 20(2), 99–104.

    PubMed  Google Scholar 

  95. Sudhalter, V., & Belser, R. C. (2001). Conversational characteristics of children with fragile X syndrome: Tangential language. American Journal on Mental Retardation, 106, 389–400.

    PubMed  Google Scholar 

  96. Sudhalter, V., Cohen, I., Silverman, W., & Wolf-Schein, E. (1990). Conversational analysis of males with fragile X, Down syndrome, and autism: Comparison of the emergence of deviant language. American Journal on Mental Retardation, 94, 431–441.

    PubMed  Google Scholar 

  97. Tager-Flusberg, H., & Sullivan, K. (1994). Predicting and explaining behavior: A comparison of autistic, mentally retarded and normal children. Journal of Child Psychology and Psychiatry, 35(6), 1059–1075.

    PubMed  Google Scholar 

  98. Tager-Flusberg, H., & Sullivan, K. (2000). A componential view of theory of mind: Evidence from Williams syndrome. Cognition, 76(1), 59–90.

    PubMed  Google Scholar 

  99. Talisa, V. B., Boyle, L., Crafa, D., & Kaufmann, W. E. (2014). Autism and anxiety in males with fragile X syndrome: An exploratory analysis of neurobehavioral profiles from a parent survey. American Journal of Medical Genetics, 164(5), 1198–1203.

    Google Scholar 

  100. Tassone, F., Hagerman, R. J., Ikle, D. N., Dyer, P. N., Lampe, M., Willemsen, R., et al. (1999). FMRP expression as a potential prognostic indicator in fragile X syndrome. American Journal of Medical Genetics, 84(3), 250–261.

    PubMed  Google Scholar 

  101. Tek, S., Mesite, L., Fein, D., & Naigles, L. (2014). Longitudinal analyses of expressive language development reveal two distinct language profiles among young children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 44, 75–89.

    PubMed  PubMed Central  Google Scholar 

  102. Thurman, A. J., McDuffie, A., Hagerman, R. J., & Abbeduto, l (2014). Psychiatric symptoms in boys with fragile X syndrome: A comparison with nonsyndromic autism spectrum disorder. Research in Developmental Disabilities, 35, 1072–1086.

    PubMed  PubMed Central  Google Scholar 

  103. Thurman, A. J., McDuffie, A., Josol, C., Hagerman, R. J., & Abbeduto, L. (2017). Language skills of males with fragile X syndrome or nonsyndromic autism spectrum disorder. Journal of Autism and Developmental Disorders, 47, 728–743.

    PubMed  PubMed Central  Google Scholar 

  104. 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 ASD. Journal of Autism and Developmental Disorders, 45, 2816–2832.

    PubMed  PubMed Central  Google Scholar 

  105. van Steensel, F. J., Bögels, S. M., & Perrin, S. (2011). Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis. Clinical, Child, and Family Psychology Review, 14, 302–317.

    Google Scholar 

  106. Waterhouse, L., & Gillberg, C. (2014). Why autism must be taken apart. Journal of Autism and Developmental Disorders, 44(7), 1788–1792.

    PubMed  Google Scholar 

  107. Waterhouse, L., London, E., & Gillberg, C. (2017). The ASD diagnosis has blocked the discovery of valid biological variation in neurodevelopmental social impairment. Autism Research, 10(7), 1182.

    PubMed  Google Scholar 

  108. Weller, E. B., Weller, R. A., Fristad, M. A., Rooney, M. T., & Schecter, J. (2000). Children’s interview for psychiatric syndromes (ChIPS). Journal of American Academy of Child and Adolescent Psychiatry, 39, 76–84.

    Google Scholar 

  109. White, S. W., Oswald, D., Ollendick, T., & Scahill, L. (2009). Anxiety in children and adolescents with autism spectrum disorders. Clinical Psychology Reviews, 29, 216–229.

    Google Scholar 

  110. Wolff, J. J., Bodfish, J. W., Hazlett, H. C., Lightbody, A. A., Reiss, A. L., & Piven, J. (2012). Evidence of a distinct behavioral phenotype in young boys with fragile X syndrome and autism. Journal of the American Academy of Child and Adolescent Psychiatry, 51(12), 1324–1332.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the families who participated in the project. The authors also thank the many research staff involved in the project, but especially Alicia Cox, Joan Gunther, Leona Kelly, Debra Reisinger, Emily Schwoerer, and Stephanie Summers.

Funding

This research was supported by grants R01HD024356 and U54HD079125 from the National Institutes of Health awarded to Leonard Abbeduto, grant F32DC013934 to Jessica Klusek, grants R01MH090194 and R01MH107573 to Jane E. Roberts, and by grant UL1TR001860 to University of California, Davis.

Author information

Affiliations

Authors

Contributions

LA conceived of the study, participated in its design and coordination, performed the statistical analysis, drafted the manuscript, and conceptualized and received funding for the larger project from which the data for this study were drawn; AJT participated in the design, data collection, data preparation, and interpretation of the data; AM participated in the design, data collection, and interpretation of the data; JK participated in the design, data collection, and interpretation of the data; RTF participated in data collection and interpretation of the data; WTB participated in the design of the study and interpretation of the data; DJH participated in the conceptualization of the statistical analysis and the interpretation of the data; TA, GL, and CD all helped perform the analysis of the biological measures and interpretation of the data; and JER helped conceive of the larger study from which the data were drawn and participated in the design, coordination, and interpretation of the data for this study. All authors helped to draft the manuscript, and read and approved the final manuscript.

Corresponding author

Correspondence to Leonard Abbeduto.

Ethics declarations

Conflict of interest

Leonard Abbeduto has received funding to develop and implement outcome measures for clinical trials from F. Hoffman-LaRoche, Ltd., Roche TCRC, Inc., Neuren Pharmaceuticals Limited, and Fulcrum Therapeutics, Inc. W. Ted Brown and Giuseppe LaFauci hold a patent for a measure used in this study [System and Method for Quantifying Fragile X Mental 1 Protein in tissue and blood samples (United States Patent # 8628934)], with the assignee for the patent being the Research Foundation for Mental Hygiene, Inc. No other authors have conflicts or financial disclosures to declare.

Ethical Approval

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. All authors obtained review and approval from the Institutional review boards of their respective universities/institutions. This article does not contain any studies with animals performed by any of the authors.

Informed Consent

was obtained from all individual participants included in the study or from their legally authorized representatives.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Abbeduto, L., Thurman, A.J., McDuffie, A. et al. ASD Comorbidity in Fragile X Syndrome: Symptom Profile and Predictors of Symptom Severity in Adolescent and Young Adult Males. J Autism Dev Disord 49, 960–977 (2019). https://doi.org/10.1007/s10803-018-3796-2

Download citation

Keywords

  • Fragile X syndrome
  • Autism spectrum disorder
  • Language
  • IQ
  • Psychiatric symptoms
  • FMRP