Journal of Autism and Developmental Disorders

, Volume 48, Issue 6, pp 1982–1994 | Cite as

Autism Spectrum Symptomatology Among Children with Duplication 7q11.23 Syndrome

  • Bonita P. Klein-TasmanEmail author
  • Carolyn B. Mervis
Original Paper


Gold-standard diagnostic assessments of autism spectrum disorder (ASD) symptomatology were conducted on 63 children (mean CA: 8.81 years) with 7q11.23 duplication syndrome, one of the copy number variants identified by Sanders et al. (Neuron 70:863–885, 2011a) as associated with ASD. ASD classification rate was 39.6% for the Autism Diagnostic Interview-Revised and 25.4% for the Autism Diagnostic Observation Schedule-2 (ADOS-2). Based on these assessments combined with clinical judgment, 19.0% of children were diagnosed with ASD. Reasons for these discrepancies are discussed, as are differences in rate of diagnosis as a function of sex, age, and ADOS-2 module administered and differences in intellectual and adaptive behavior abilities as a function of presence or absence of ASD diagnosis and ADOS-2 module administered. Implications are addressed.


7q11.23 duplication syndrome Autism spectrum disorders Social anxiety Selective mutism 



This project was supported by a grant from the Simons Foundation (SFARI award #238896). We would like to thank the children and parents who participated in this study; their generosity made this research possible. We also would like to thank Kristin Smith, Brianna Yund, and the members of the Neurodevelopmental Sciences Laboratory (especially C. Holley Pitts) for assistance with data collection and statistical analyses.

Author Contributions

BPKT and CBM conceptualized and designed the study. CBM coordinated participant recruitment, conducted the adaptive behavior interviews, and supervised the intellectual and language testing. BPKT conducted and/or oversaw all ASD-related assessments and the ADIS-P interviews. BPKT conducted the analyses and BPKT and CBM worked together on interpretation of the results. BPKT drafted the manuscript which was reviewed and edited together with CBM. Both authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest to report.

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.


  1. Achenbach, T. M., & Rescorla, L. A. (2001). Manual for the ASEBA school-age forms and profiles. Burlington, VT: University of Vermont.Google Scholar
  2. Aman, M. G., Singh, N. N., Stewart, A. W., & Field, C. J. (1985). Psychometric characteristics of the Aberrant Behavior Checklist. American Journal of Mental Deficiency, 89, 492–502.PubMedGoogle Scholar
  3. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5. Washington, DC: Author.CrossRefGoogle Scholar
  4. Belmonte, M. K., & Bourgeron, T. (2006). Fragile X syndrome and autism at the intersection of genetic and neural networks. Nature Neuroscience, 9, 1221–1225.CrossRefPubMedGoogle Scholar
  5. Berg, J. S., Brunetti-Pierri, N., Peters, S. U., Kang, S. H., Fong, C. T., Salamone, J. … Cheung, S. W. (2007). Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genetics in Medicine, 9, 427–441. Scholar
  6. Berument, S. K., Rutter, M., Lord, C., Pickles, A., & Bailey, A. (1999). Autism screening questionnaire: Diagnostic validity. British Journal of Psychiatry, 175, 444–451.CrossRefPubMedGoogle Scholar
  7. Betancur, C. (2011). Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting. Brain Research, 1380, 42–77. Scholar
  8. Bruininks, R. H., Woodcock, R. W., Weatherman, R. F., & Hill, B. K. (1996). Scales of Independent Behavior—Revised. Itasca, IL: Riverside Publishing.Google Scholar
  9. Budimirovic, D. B., & Kaufmann, W. E. (2011). What can we learn about autism from studying fragile X syndrome? Developmental Neuroscience, 33, 379–394. Scholar
  10. Crespi, B. J., & Procyshyn, T. L. (2017). Williams syndrome deletions and duplications: Genetic windows to understanding anxiety, sociality, autism, and schizophrenia. Neuroscience and Biobehavioral Reviews, 79, 14–26. Scholar
  11. Daniels, A. M., & Mandell, D. S. (2014). Explaining differences in age at autism spectrum disorder diagnosis: A critical review. Autism: The International Journal of Research and Practice, 18, 583–597. Scholar
  12. Dixit, A., McKee, S., Mansour, S., Mehta, S. G., Tanteles, G. A., Anastasiadou, V. … Sarkar, A (2013). 7q11.23 microduplication: A recognizable phenotype. Clinical Genetics, 83, 155–161. Scholar
  13. Dunn, L. M., & Dunn, D. M. (2007). Peabody Picture Vocabulary Test-4. Minneapolis, MN: Pearson.Google Scholar
  14. Dykens, E. M., Roof, E., Hunt-Hawkins, H., Dankner, N., Lee, E. B., Shivers, C. M. … Kim, S. J. (2017). Diagnoses and characteristics of autism spectrum disorders in children with Prader-Willi syndrome. Journal of Neurodevelopmental Disorders. Scholar
  15. Elliott, C. D. (2007). Differential ability scales (2nd edn.). San Antonio, TX: Psychological Corporation.Google Scholar
  16. Fombonne, E. (2009). Epidemiology of pervasive developmental disorders. Pediatric Research, 65, 591–598. Scholar
  17. Geschwind, D. H. (2011). Genetics of autism spectrum disorders. Trends in Cognitive Sciences, 15, 409–416. Scholar
  18. Gotham, K., Pickles, A., & Lord, C. (2009). Standardizing ADOS scores for a measure of severity in autism spectrum disorders. Journal of Autism and Developmental Disorders, 39, 693–705. Scholar
  19. Gotham, K., Risi, S., Pickles, A., & Lord, C. (2007). The autism diagnostic observation schedule: Revised algorithms for improved diagnostic validity. Journal of Autism and Developmental Disorders, 37, 613–627. Scholar
  20. Halladay, A. K., Bishop, S., Constantino, J. N., Daniels, A. M., Koenig, K., Palmer, K. … Szatmari, P. (2015). Sex and gender differences in autism spectrum disorder: Summarizing evidence gaps and identifying emerging areas of priority. Molecular Autism. Scholar
  21. Happé, F., Ronald, A., & Plomin, R. (2006). Time to give up on a single explanation for autism. Nature Neuroscience, 9, 1218–1220CrossRefPubMedGoogle Scholar
  22. Howlin, P., & Asgharian, A. (1999). The diagnosis of autism and Asperger syndrome: Findings from a survey of 770 families. Developmental Medicine and Child Neurology, 41, 834–839.CrossRefPubMedGoogle Scholar
  23. IBM Corp (2016). IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.Google Scholar
  24. Jónsdóttir, S. L., Saemundsen, E., Antonsdóttir, I. S., Sigurdardóttir, S., & Ólason, D. (2011). Children diagnosed with autism spectrum disorder before or after the age of 6 years. Research in Autism Spectrum Disorders, 5, 175–184. Scholar
  25. Klein-Tasman, B. P., Li-Barber, K. T., & Magargee, E. T. (2011). Honing in on the social phenotype in Williams syndrome using multiple measures and multiple raters. Journal of Autism and Developmental Disorders, 41, 341–351.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Klein-Tasman, B. P., Mervis, C. B., Lord, C. E., & Phillips, K. D. (2007). Socio-communicative deficits in young children with Williams syndrome: Performance on the autism diagnostic observation schedule. Child Neuropsychology, 13, 444–467.CrossRefPubMedGoogle Scholar
  27. Klein-Tasman, B. P., Phillips, K. D., Lord, C., Mervis, C. B., & Gallo, F. G. (2009). Overlap with the autism spectrum in young children with Williams syndrome. Journal of Developmental and Behavioral Pediatrics, 30, 289–299.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Levy, D., Ronemus, M., Yamrom, B., Lee, Y. H., Leotta, A., Kendall, J. … Wigler, M. (2011). Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron, 70, 886–897. Scholar
  29. Lincoln, A. J., Searcy, Y. M., Jones, W., & Lord, C. (2007). Social interaction behaviors discriminate young children with autism and Williams syndrome. Journal of the American Academy of Child and Adolescent Psychiatry, 46, 323–331. Scholar
  30. Lord, C., Rutter, M., DiLavore, P., & Risi, S. (1999). Autism diagnostic observation schedule (ADOS) manual. Los Angeles, CA: Western Psychological Services.Google Scholar
  31. Lord, C., Rutter, M., DiLavore, P. C., Risi, S., Gotham, K., & Bishop, S. L. (2012). Autism diagnostic observation schedule (2nd edn.). Los Angeles, CA: Western Psychological Services.Google Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. Malenfant, P., Liu, X., Hudson, M. L., Qiao, Y., Hrynchak, M., Riendeau, N. … Holden, J. J. (2012). Association of GTF2i in the Williams-Beuren syndrome critical region with autism spectrum disorders. Journal of Autism and Developmental Disorders, 42, 1459–1469. Scholar
  34. Mandell, D. S., Novak, M. M., & Zubritsky, C. D. (2005). Factors associated with age of diagnosis among children with autism spectrum disorders. Pediatrics,. 116, 1480–1486.Google Scholar
  35. McGrew, S. G., Peters, B. R., Crittendon, J. A., & Veenstra-Vanderweele, J. (2012). Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: Which guidelines to implement? Journal of Autism and Developmental Disorders, 42, 1582–1591. Scholar
  36. Mervis, C. B., Klein-Tasman, B. P., Huffman, M. J., Velleman, S. L., Pitts, C. H., Henderson, D. R. … Osborne, L. R. (2015). Children with 7q11.23 duplication syndrome: Psychological characteristics. American Journal of Medical Genetics Part A, 167, 1436–1450. Scholar
  37. Morris, C. A., Mervis, C. B., Paciorkowski, A. P., Abdul-Rahman, O., Dugan, S. L., Rope, A. F. … Osborne, L. R. (2015). 7q11.23 duplication syndrome: Physical characteristics and natural history. American Journal of Medical Genetics Part A, 167, 2916–2935. Scholar
  38. Persico, A. M., & Bourgeron, T. (2006). Searching for ways out of the autism maze: Genetic, epigenetic and environmental clues. Trends in Neurosciences, 29, 349–358.CrossRefPubMedGoogle Scholar
  39. Picci, G., & Scherf, K. S. (2015). A two-hit model of autism: Adolescence as the second hit. Clinical Psychological Science, 3, 349–371. Scholar
  40. Ronald, A., Happe, F., Price, T. S., Baron-Cohen, S., & Plomin, R. (2006). Phenotypic and genetic overlap between autistic traits at the extremes of the general population. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 1206–1214. Scholar
  41. Rutter, M., Bailey, A., & Lord, C. (2003). Social communication questionnaire. Los Angeles: Western Psychological Services.Google Scholar
  42. Sanders, S. J., Ercan-Sencecek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D. … State, M. W. (2011b). Supplemental materials. Neuron. Retrieved from
  43. Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D. … State, M. W. (2011a). Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron, 70, 863–885. Scholar
  44. Silverman, W. K., & Albano, A. M. (1996). The anxiety disorders interview schedule for DSM-IV: Parent interview schedule. San Antonio, TX: Psychological Corporation.Google Scholar
  45. Somerville, M. J., Mervis, C. B., Young, E. J., Seo, E. J., del Campo, M., Bamforth, S. … Osborne, L. R. (2005). Severe expressive-language delay related to duplication of the Williams-Beuren locus. The New England Journal of Medicine, 353, 1694–1701.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Strong, E., Butcher, D. T., Singhania, R., Mervis, C. B., Morris, C. A., De Carvalho, D. … Osborne, L. R. (2015). Symmetrical dose-dependent DNA-methylation profiles in children with deletion or duplication of 7q11.23. American. Journal of Human Genetics, 97, 216–227. Scholar
  47. Van der Aa, N., Rooms, L., Vandeweyer, G., van den Ende, J., Reyniers, E., Fichera, M. … Kooy, R. F. (2009). Fourteen new cases contribute to the characterization of the 7q11.23 microduplication syndrome. European Journal of Medical Genetics, 52, 94–100. Scholar
  48. van der Fluit, F. (2014). Autism Spectrum Disorder symptomatology in verbal children with Williams syndrome (Dissertation). Retrieved from UWM Digital Commons (Number 772).
  49. Werling, D. M., & Geschwind, D. H. (2013). Understanding sex bias in autism spectrum disorder. Proceedings of the National Academy of Sciences of the United States of America, 110, 4868–4869. Scholar
  50. Wiggins, L. D., Baio, J., & Rice, C. (2006). Examination of the time between first evaluation and first autism spectrum diagnosis in a population-based sample. Journal of Developmental and Behavioral Pediatrics, 27(2 Suppl), S79–S87.CrossRefPubMedGoogle Scholar
  51. Williams, K. T. (2007). Expressive Vocabulary Test-2. Minneapolis, MN: Pearson.Google Scholar
  52. Wing, L., & Gould, J. (1979). Severe impairments of social interaction and associated abnormalities in children: Epidemiology and classification. Journal of Autism and Developmental Disorders, 9, 11–29.CrossRefPubMedGoogle Scholar
  53. Zhao, X., Leotta, A., Kustanovich, V., Lajonchere, C., Geschwind, D. H., Law, K. … Wigler, M. (2007). A unified genetic theory for sporadic and inherited autism. Proceedings of the National Academy of Sciences of the United States of America, 104, 12831–12836.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of Wisconsin-MilwaukeeMilwaukeeUSA
  2. 2.Department of Psychological and Brain SciencesUniversity of LouisvilleLouisvilleUSA

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