Encyclopedia of Clinical Neuropsychology

2018 Edition
| Editors: Jeffrey S. Kreutzer, John DeLuca, Bruce Caplan

Duplication 7 Syndrome

  • Bonita P. “Bonnie” Klein-TasmanEmail author
  • Carolyn B. Mervis
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-57111-9_9140


Duplication of the Williams syndrome region; Williams-Beuren region duplication syndrome (OMIM 609757)

Short Description or Definition

7q11.23 duplication syndrome (Dup7) results from a recurrent 1.5- to 1.8-Mb heterozygous duplication of the same genetic region deleted in Williams syndrome. All individuals with Dup7 show some effects of the duplication, but the expression of the phenotype is variable. Dup7 is associated with a characteristic facial appearance. Medically, individuals with Dup7 are at increased risk of heart disease (especially aortic dilation), macrocephaly, hydrocephalus, severe constipation, and seizures. Almost all individuals with Dup7 show speech delays and impairments in childhood. Common difficulties include language delay or impairment, learning problems, developmental coordination disorder, social anxiety, selective mutism, attention problems, autism spectrum symptomatology, aggression, and oppositionality. There is a wide range of intellectual...

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References and Readings

  1. Belmonte, M. K., & Bourgeron, T. (2006). Fragile X syndrome and autism at the intersection of genetic and neural networks. Nature Neuroscience, 9(10), 1221–1225. nn1765 [pii].PubMedCrossRefPubMedCentralGoogle Scholar
  2. 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(7), 427–441.  https://doi.org/10.1097/GIM.0b013e3180986192.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Berg, J. S., Potocki, L., & Bacino, C. A. (2010). Common recurrent microduplication syndromes: Diagnosis and management in clinical practice. American Journal of Medical Genetics. Part A, 152A(5), 1066–1078.  https://doi.org/10.1002/ajmg.a.33185.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Betancur, C. (2011). Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting. Brain Research, 1380, 42–77.  https://doi.org/10.1016/j.brainres.2010.11.078.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Beunders, G., van de Kamp, J. M., Veenhoven, R. H., van Hagen, J. M., Nieuwint, A. W., & Sistermans, E. A. (2010). A triplication of the Williams-Beuren syndrome region in a patient with mental retardation, a severe expressive language delay, behavioural problems and dysmorphisms. Journal of Medical Genetics, 47(4), 271–275.  https://doi.org/10.1136/jmg.2009.070490.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bodfish, J. W., Symons, F. J., Parker, D. E., & Lewis, M. H. (2000). Varieties of repetitive behavior in autism: Comparisons to mental retardation. Journal of Autism and Developmental Disorders, 30(3), 237–243.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Budimirovic, D. B., & Kaufmann, W. E. (2011). What can we learn about autism from studying fragile X syndrome? Developmental Neuroscience, 33(5), 379–394.  https://doi.org/10.1159/000330213.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Daniels, A. M., & Mandell, D. S. (2014). Explaining differences in age at autism spectrum disorder diagnosis: A critical review. Autism, 18(5), 583–597.  https://doi.org/10.1177/1362361313480277.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Davidovitch, M., Levit-Binnun, N., Golan, D., & Manning-Courtney, P. (2015). Late diagnosis of autism spectrum disorder after initial negative assessment by a multidisciplinary team. Journal of Developmental and Behavioral Pediatrics: JDBP, 36(4), 227–234.  https://doi.org/10.1097/DBP.0000000000000133.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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(2), 155–161.  https://doi.org/10.1111/j.1399-0004.2012.01862.x.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Geschwind, D. H. (2011). Genetics of autism spectrum disorders. Trends in Cognitive Sciences, 15(9), 409–416.  https://doi.org/10.1016/j.tics.2011.07.003.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Happe, F., Ronald, A., & Plomin, R. (2006). Time to give up on a single explanation for autism. Nature Neuroscience, 9(10), 1218–1220.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 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(1), 175–184.  https://doi.org/10.1016/j.rasd.2010.03.007.CrossRefGoogle Scholar
  14. 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(5), 886–897.  https://doi.org/10.1016/j.neuron.2011.05.015.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Lord, C., Risi, S., Lambrecht, L., Cook Jr., E. H., Leventhal, B. L., DiLavore, P. C., …, Rutter, M. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30(3), 205–223.Google Scholar
  16. Magnúsdóttir, K., Saemundsen, E., Einarsson, B. L., Magnússon, P., & Njardvik, U. (2016). The impact of attention deficit/hyperactivity disorder on adaptive functioning in children diagnosed late with autism spectrum disorder—A comparative analysis. Research in Autism Spectrum Disorders, 23, 28–35.  https://doi.org/10.1016/j.rasd.2015.11.012.CrossRefGoogle Scholar
  17. 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(7), 1459–1469.  https://doi.org/10.1007/s10803-011-1389-4.CrossRefGoogle Scholar
  18. 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(8), 1582–1591.  https://doi.org/10.1007/s10803-011-1398-3.CrossRefGoogle Scholar
  19. Mervis, C. B., Dida, J., Lam, E., Crawford-Zelli, N. A., Young, E. J., Henderson, D. R., …, Osborne, L. R. (2012). Duplication of GTF2I results in separation anxiety in mice and humans. American Journal of Human Genetics, 90(6), 1064–1070.  https://doi.org/10.1016/j.ajhg.2012.04.012.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Mervis, C. B., Klein-Tasman, B. P., Huffman, M. J., Velleman, S. L., Pitts, C. H., Henderson, D. R., …, Osborne, L. R. (2015a). Children with 7q11.23 duplication syndrome: Psychological characteristics. American Journal of Medical Genetics Part A, 167(7), 1436–1450.  https://doi.org/10.1002/ajmg.a.37071.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Mervis, C. B., Morris, C. A., Klein-Tasman, B. P., Velleman, S. L., & Osborne, L. R. (2015b). 7q11.23 duplication syndrome. In R. A. Pagon, M. P. Adam, H. H. Ardinger, S. E. Wallace, A. Amemiya, L. J. H. Bean, …, K. Stephens (Eds.), Genereviews. Seattle: University of Washington. NBK327268.Google Scholar
  22. Mervis, C. B., & Velleman, S. L. (2011). Children with Williams syndrome: Language, cognitive, and behavioral characteristics and their implications for intervention. Perspectives on Language Learning and Education, 18(3), 98–107.  https://doi.org/10.1044/lle18.3.98.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Michelotti, J., Charman, T., Slonims, V., & Baird, G. (2002). Follow-up of children with language delay and features of autism from preschool years to middle childhood. Developmental Medicine and Child Neurology, 44(12), 812–819.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Morris, C. A., Mervis, C. B., & Osborne, L. R. (2011). Frequency of the 7q11.23 inversion polymorphism in transmitting parents of children with Williams syndrome and in the general population does not differ between North America and Europe. Molecular Cytogenetics, 4, 7-8166-4-7.  https://doi.org/10.1186/1755-8166-4-7.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 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(12), 2916–2935.  https://doi.org/10.1002/ajmg.a.37340.CrossRefGoogle Scholar
  26. Mulle, J. G., Pulver, A. E., McGrath, J. A., Wolyniec, P. S., Dodd, A. F., Cutler, D. J., …, Warren, S. T. (2014). Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia. Biological Psychiatry, 75(5), 371–377.  https://doi.org/10.1016/j.biopsych.2013.05.040.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Osborne, L. R., & Mervis, C. B. (2007). Rearrangements of the Williams-Beuren syndrome locus: Molecular basis and implications for speech and language development. Expert Reviews in Molecular Medicine, 9(15), 1–16. S146239940700035X.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Persico, A. M., & Bourgeron, T. (2006). Searching for ways out of the autism maze: Genetic, epigenetic and environmental clues. Trends in Neurosciences, 29(7), 349–358. S0166-2236(06)00111-1.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Picci, G., & Scherf, K. S. (2015). A two-hit model of autism: Adolescence as the second hit. Clinical Psychological Science, 3(3), 349–371.  https://doi.org/10.1177/2167702614540646.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Pickles, A., Starr, E., Kazak, S., Bolton, P., Papanikolaou, K., Bailey, A., …, Rutter, M. (2000). Variable expression of the autism broader phenotype: Findings from extended pedigrees. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 41(4), 491–502.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Piven, J., Palmer, P., Jacobi, D., Childress, D., & Arndt, S. (1997). Broader autism phenotype: Evidence from a family history study of multiple-incidence autism families. The American Journal of Psychiatry, 154(2), 185–190.  https://doi.org/10.1176/ajp.154.2.185.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Risi, S., Lord, C., Gotham, K., Corsello, C., Chrysler, C., Szatmari, P., …, Pickles, A. (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.  https://doi.org/10.1097/01.chi.0000227880.42780.0e.CrossRefGoogle Scholar
  33. Ronald, A., Happe, F., Bolton, P., Butcher, L. M., Price, T. S., Wheelwright, S., …, Plomin, R. (2006a). Genetic heterogeneity between the three components of the autism spectrum: A twin study. Journal of the American Academy of Child and Adolescent Psychiatry, 45(6), 691–699.  https://doi.org/10.1097/01.chi.0000215325.13058.9d.CrossRefGoogle Scholar
  34. Ronald, A., Happe, F., Price, T. S., Baron-Cohen, S., & Plomin, R. (2006b). 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(10), 1206–1214.  https://doi.org/10.1097/01.chi.0000230165.54117.41.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Saemundsen, E., Magnusson, P., Georgsdottir, I., Egilsson, E., & Rafnsson, V. (2013). Prevalence of autism spectrum disorders in an icelandic birth cohort. BMJ Open, 3(6).  https://doi.org/10.1136/bmjopen-2013-002748.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., …, State, M. W. (2011). Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron, 70(5), 863–885.  https://doi.org/10.1016/j.neuron.2011.05.002.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 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(16), 1694–1701.. 353/16/1694.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 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(2), 216–227.  https://doi.org/10.1016/j.ajhg.2015.05.019.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Tam, E., Young, E. J., Morris, C. A., Marshall, C. R., Loo, W., Scherer, S. W., …, Osborne, L. R. (2008). The common inversion of the Williams-Beuren syndrome region at 7q11.23 does not cause clinical symptoms. American Journal of Medical Genetics Part A, 146A(14), 1797–1806.  https://doi.org/10.1002/ajmg.a.32360.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Torniero, C., Dalla Bernardina, B., Novara, F., Cerini, R., Bonaglia, C., Pramparo, T., …, Zuffardi, O. (2008). Dysmorphic features, simplified gyral pattern and 7q11.23 duplication reciprocal to the Williams-Beuren deletion. European Journal of Human Genetics, 16(8), 880–887.  https://doi.org/10.1038/ejhg.2008.42.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 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(2-3), 94–100.  https://doi.org/10.1016/j.ejmg.2009.02.006.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Velleman, S. L., & Mervis, C. B. (2011). Children with 7q11.23 duplication syndrome: Speech, language, cognitive, and behavioral characteristics and their implications for intervention. Perspectives on Language Learning and Education, 18(3), 108–116.  https://doi.org/10.1044/lle18.3.108.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 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(31), 12831–12836. 0705803104.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Bonita P. “Bonnie” Klein-Tasman
    • 1
    Email author
  • Carolyn B. Mervis
    • 2
  1. 1.Department of PsychologyUniversity of Wisconsin-MilwaukeeMilwaukeeUSA
  2. 2.Department of Psychological and Brain SciencesUniversity of LouisvilleLouisvilleUSA