Skip to main content
Log in

Autism Spectrum Phenotype in Males and Females with Fragile X Full Mutation and Premutation

Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

The behavioural phenotype of autism was assessed in individuals with full mutation and premutation fragile X syndrome (FXS) using the Autism Diagnostic Observation Scale-Generic (ADOS-G) and the Autism Diagnostic Interview (ADI-R). The participants, aged 5–80 years, comprised 33 males and 31 females with full mutation, 7 males and 43 females with premutation, and 38 non-fragile X relatives (29 males, 9 females). In the full mutation group, a total of 67% males and 23% females met either the Autism Disorder (AD) or the Autism Spectrum Disorder (ASD) criteria on at least one of the diagnostic tests. In the premutation group, 14% males and 5% females met the ADOS-G criteria for ASD. The presence of autism manifestations in males and females with full mutation and premutation provide support for a spectrum view.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. The rating of seven is given when abnormal behaviour of a type that is not encompassed by the other ratings is apparent, and eight is assigned when the behaviour does not occur and/or the rating is not applicable. These latter ratings cannot be used in the algorithm and are therefore given sparingly.

References

  • American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed., text revised.). Washington, DC: American Psychiatric Association.

    Google Scholar 

  • Bailey, A., Bolton, P., Butler, L., Le Couteur, A., Murphy, M., Scott, S., Webb, T., & Rutter, M. (1993). Prevalence of the fragile X anomaly amongst autistic twins and singletons. Journal of Child Psychology and Psychiatry, 34, 673–688.

    Article  PubMed  Google Scholar 

  • Bailey, D. B., 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, 49–59.

    Article  PubMed  Google Scholar 

  • Bailey, D. B., 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, 165–174.

    Article  PubMed  Google Scholar 

  • Bailey, D. B., Mesibov, G. B., Hatton, D. D., Clark, R. D., Roberts, J. E., & Mayhew, L. (1998). Autistic behavior in young boys with Fragile X syndrome. Journal of Autism and Developmental Disorders, 28, 499–508.

    Article  PubMed  Google Scholar 

  • Bailey, A., Palferman, S., Heavey, L., & Le Couteur, A. (1998). Autism: The phenotype in relatives. Journal of Autism and Developmental Disorders, 28, 369–392.

    Article  PubMed  Google Scholar 

  • Bailey, A., Phillips, W., & Rutter, M. (1996). Autism: Towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. Journal of Child Psychology and Psychiatry, 37, 89–126.

    Article  PubMed  Google Scholar 

  • Baumgardner, T., Reiss, A. L., Freund, L., & Abrams, M. (1995). Specification of the neurobehavioural phenotype in males with fragile X syndrome. Pediatrics, 95, 744–752.

    PubMed  Google Scholar 

  • Brown, W.T., Jenkins, E.C., Cohen, I.L., Fisch, G.S., Wolf-Schein, E.G., Gross, A., Waterhouse, L., Fein, D., Mason-Brothers, A., & Ritvo, E. (1986). Fragile X and autism: A multicenter survey. American Journal of Medical Genetics, 23, 341–352.

    Article  PubMed  Google Scholar 

  • Brown, W. T., Jenkins, E. C., Friedman, E., Brooks, J., Wisniewski, K., Raguthu, S., & French, J. (1982). Autism is associated with the fragile-X syndrome. Journal of Autism and Developmental Disordesr, 12, 303–308.

    Article  Google Scholar 

  • Cohen, I. L. (1995). Behavioural profiles of autistic and non-autistic fragile X males. Mental Retardation and Developmental Disabilities Research Reviews, 1, 286–291.

    Article  Google Scholar 

  • Cook, E. H. (2001). Genetics of autism. Child and Adolescent Psychiatry Clinics of North America, 10, 333–350.

    Google Scholar 

  • de Vries, B. B., Wiegers, A. M., Smits, A. P., Mohkamsing, S., Duivenvoorden, H. J., Fryns, J. P., Curfs, L. M., Halley, D. J., Oostra, B. A., van den Ouweland, A. M., & Niermeijer, M. F. (1996). Mental status of females with an FMR1 gene full mutation. American Journal of Medical Genetics, 58, 1025–1032.

    Google Scholar 

  • Dykens, E. M., & Volkmar, F. R. (1997). Medical conditions associated with autism. In D. J. Cohen, & F. R. Volkmar, (Eds.), Handbook of autism and pervasive developmental disorders. (2nd ed.) (pp. 388–410). New York: Wiley.

    Google Scholar 

  • Feinstein, C., & Reiss, A. L. (1998). Autism: The point of view from fragile X studies. Journal of Autism and Developmental Disorders, 28, 393–405.

    Article  PubMed  Google Scholar 

  • Fisch, G. S. (1993). What is associated with the fragile X syndrome. American Journal of Medical Genetics, 48, 112–121.

    Article  PubMed  Google Scholar 

  • Fombonne, E. (2003). Epidemiological surveys of autism and other pervasive developmental disorders: An update. Journal of Autism and Developmental Disorders, 33, 365–382.

    Article  PubMed  Google Scholar 

  • Fombonne, E., Du Mazaubrun, C., Cans, C., & Grandjean, H. (1997). Autism and associated medical disorders in a French epidemiological survey. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 1561–1569.

    Article  Google Scholar 

  • Gillberg, C. (1998). Chromosomal disorders and autism. Journal of Autism and Developmental Disorders, 28, 415–425.

    Article  PubMed  Google Scholar 

  • Hagerman, R. J. (1991). Physical and behavioral phenotype. In R. J. Hagerman, & A. Silverman, (Eds.), Fragile X syndrome: Diagnosis, treatment, and research. (pp. 3–68). Baltimore: The John Hopkins University Press.

    Google Scholar 

  • Hagerman, R. J. (1999). Fragile X syndrome. In R. J. Hagerman (Ed.), Neurodevelopmental disorders: Diagnosis and treatment. (pp. 61–132). New York: Oxford University Press.

    Google Scholar 

  • Hagerman, R. J. (2002). Physical and behavioral phenotype. In R. J. Hagerman, & P. J. Hagerman, (Eds.), Fragile X syndrome: Diagnosis, treatment, and research, (3rd ed.,) (pp. 3–87). Baltimore, MD: The John Hopkins University Press.

    Google Scholar 

  • Hagerman, R. J., Jackson, A. W., Levitas, A., Rimland, B., & Braden, M. (1986). An analysis of autism in fifty males with the fragile X syndrome. American Journal of Medical Genetics, 23, 359–374.

    Article  PubMed  Google Scholar 

  • Irwin, S. A, Swain, R. A., Christmon, C. A., Chakravarti, A., Weiler, I. J., & Greenough, W. T. (2000). Evidence for altered Fragile-X mental retardation protein expression in response to behavioral stimulation. Neurobiology of Learning and Memory, 73, 87–93.

    Article  PubMed  Google Scholar 

  • Kaufmann, W. E., Cortell, R., Kau, A., Bukelis, I., Tierney, E., Gray, R. M., Cox, C., Capone, G. T., & Stanard, P. (2004). Autism Spectrum Disorder in Fragile X Syndrome: Communication, social interaction, and specific behaviors. American Journal of Medical Genetics, 129, 225–234.

    Article  PubMed  Google Scholar 

  • Kerby, D. S., & Dawson, B. L. (1994). Autistic features, personality, and adaptive behavior in males with the fragile X syndrome and no autism. American Journal of Mental Retardation, 98, 455–462.

    PubMed  Google Scholar 

  • Lachiewicz, A., Spiridigliozzi, G., Gullion, C., Ransford, S., & Rao, K. (1994). Aberrant behaviors of young boys with fragile X syndrome. American Journal of Mental Retardation, 98, 567–579.

    PubMed  Google Scholar 

  • Le Couteur, A., Bailey, A., Goode, S., Pickles, A., Robertson, S., Gottesman, I., & Rutter M. (1996). A broader phenotype of autism: The clinical spectrum of twins. Journal of Child Psychology and Psychiatry, 37, 785–802.

    Article  PubMed  Google Scholar 

  • Loesch, D. Z., Bui, Q. M., Dissanayake, C., Clifford, S., Gould, E., Bulhak-Paterson, Tassone, F., Taylor, A. K., Hessl, D., Hagerman, R., Hagerman, P., & Huggins, R. M. (submitted Sept. 2005). Autism spectrum behaviours fragile X: Gold standard assessment, and phenotypic and genetic predictors. Journal of Developmental and Behavioural Paediatrics.

  • Loesch, D. Z., & Hay, D. A. (1988). Clinical features and reproductive patterns in fragile X female heterozygotes. Journal of Medical Genetics, 25, 407–414.

    Article  PubMed  Google Scholar 

  • Loesch, D. Z., Huggins, R., Bui, Q. M., Epstein, J., Taylor, A., Hagerman, R. J. (2002). Effect of the deficits of fragile X mental retardation protein on cognitive status of fragile males and females assessed by robust pedigree analysis. Journal of Developmental and Behavioural Paediatrics, 23, 416–423.

    Google Scholar 

  • Loesch, D. Z., Sheffield, L. J., & Hay, D. A. (1993). Between-generation differences in ascertainment and penetrance: Relevance to genetic hypotheses in fragile X. Human Genetics, 91, 469–474.

    Article  PubMed  Google Scholar 

  • Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.

    Article  PubMed  Google Scholar 

  • Lord, C., Rutter, M., DiLavore, P., & Risi, S. (1999). Autism diagnostic observation schedule-WPS edition. Los Angeles, CA.: Western Psychological Services.

    Google Scholar 

  • Mazzocco, M. M., Kates, W. R., Baumgardner, T. L., Freund, L. S., & Reiss, A. L. (1997). Autistic behaviour among girls with fragile X syndrome. Journal of Autism and Developmental Disorders, 27, 415–435.

    Article  PubMed  Google Scholar 

  • 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, 64, 388–394.

    Article  PubMed  Google Scholar 

  • Miller, L. J., McIntosh, D. N., McGrath, J., Shyu, V., Lampe, M., Taylor, A. K., Tassone, F., Neitzel, K., Stackhouse, T., & Hagerman, R. J. (1999). Electrodermal responses to sensory stimuli in individuals with Fragile X Syndrome: A preliminary report. American Journal of Medical Genetics, 83, 268–279.

    Article  PubMed  Google Scholar 

  • Muhle, R., Trentacoste, S. V., & Rapin, I. (2004). The genetics of autism. Pediatrics, 113, 472–486.

    Article  Google Scholar 

  • Pieretti, M., Zhang, F., Fu, Y. H., Warren, S. T., Oostra, B. A., Caskey, C. T., & Nelson, D. L. (1991). Absence of expression of the FMR-1 gene in fragile X syndrome. Cell, 66, 817–822.

    Article  PubMed  Google Scholar 

  • Proops, R., & Webb, T. (1981). The ‘fragile’ X chromosome in the Martin-Bell-Renpenning syndrome and in males with other forms of familial mental retardation. Journal of Medical Genetics, 18, 366–373.

    PubMed  Google Scholar 

  • Reiss, A. L., & Freund, L. (1990). Fragile X syndrome, DSM-III-R, and autism. Journal of the American Academy of Child and Adolescent Psychiatry, 29, 885–891.

    Article  PubMed  Google Scholar 

  • Rutter, M., Bailey, A., Berument, S. K., Le Couteur, A., Lord, C., & Pickles, A. (2001; Prepublication). Social communication questionnaire: lifetime version. Los Angeles, CA: Western Psychological Services.

    Google Scholar 

  • Rogers, S. J., Wehner, E., & Hagerman, R. J. (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 Behavioural Paediatrics, 22, 409–417.

    Google Scholar 

  • Schopler, E., Reichler, R. J., & Renner, B. R (1988). The Childhood Autism Rating Scale. Los Angeles, CA: Western Psychological Services.

    Google Scholar 

  • Sparrow, S. S., Balla, D. A., & Cicchetti, D. (1984). Vineland adaptive behavior scales. Circle Pines, MN: American Guidance Service.

    Google Scholar 

  • Taylor, A. K., Safanda, J. F., Fall, M. Z., Quince, C., Lang, K. A., Hull, C. E., Carpenter, I., Staley, L. W., Hagerman, R. J. (1994). Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. JAMA, 271, 507–514.

    Article  PubMed  Google Scholar 

  • Thompson, E. A. (1993). Sampling and ascertainment in genetic epidemiology. A tutorial review. (Unpublished Manuscript) Department of Statistics. University of Washington.

  • Turner, G., Daniel, A., & Frost, M. (1980). X-linked mental retardation, macro-orchidism and the Xq27 fragile site. Journal of Pediatrics, 96, 837–841.

    Article  PubMed  Google Scholar 

  • Turk, J., & Graham, P. (1997). Fragile X syndrome, autism, and autistic features. Autism, 1, 175–197.

    Article  Google Scholar 

  • Wechsler, D. (1991). Wechsler intelligence scale for children (3rd ed.,) San Antonio: The Psychological Corporation.

    Google Scholar 

  • Wechsler, D. (1997). Wechsler adult intelligence scale. (3rd ed.,) San Antonio: The Psychological Corporation.

    Google Scholar 

  • Wechsler, D. (2002). Wechsler preschool and primary scale of intelligence (3rd ed.) San Antonio: The Psychological Corporation.

    Google Scholar 

  • Weiler, I. J., & Greenough, W. T. (1999). Synaptic synthesis of the Fragile X protein: Possible involvement in synapse maturation and elimination. American Journal of Medical Genetics, 83, 248–252.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge receipt of the National Institutes of Health Grant No. HD36071, and Grant No. 5MO1RR00069, General Clinical Research Centers Program, National Center for Research Resources, NIH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cheryl Dissanayake.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clifford, S., Dissanayake, C., Bui, Q.M. et al. Autism Spectrum Phenotype in Males and Females with Fragile X Full Mutation and Premutation. J Autism Dev Disord 37, 738–747 (2007). https://doi.org/10.1007/s10803-006-0205-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-006-0205-z

Keywords

Navigation