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Journal of Autism and Developmental Disorders

, Volume 43, Issue 10, pp 2484–2490 | Cite as

Brief Report: Regression Timing and Associated Features in MECP2 Duplication Syndrome

  • S. U. Peters
  • R. J. Hundley
  • A. K. Wilson
  • C. M. B. Carvalho
  • J. R. Lupski
  • M. B. Ramocki
Brief Report

Abstract

The aim of this study was to determine the frequency, timing, and associated features of developmental regression in MECP2 duplication syndrome. We also examined whether duplication size was associated with regression. Comprehensive psychological evaluations were used to assess 17 boys with MECP2 duplication syndrome. Information about regression was gathered via parent report. Eight of 17 boys exhibited regression in language skills, while seven of 17 exhibited regression in other skill areas. Regression in “other skill” areas coincided with seizure onset and with a prior autism diagnosis in six of seven participants. Regression was not associated with duplication size. Questions remain as to why some boys regress, and future work is necessary to understand the underlying mechanism(s) that causes regression.

Keywords

Regression MECP2 Seizures 

Notes

Acknowledgments

Funding for this project has been provided by a Vanderbilt Kennedy Center Hobbs Discovery Grant (to SUP), by 5P30HD015052-30 (to Elisabeth Dykens PI), and by NINDS grant 5K08NS062711 (to M.B.R.). We also wish to thank the individuals and families who so graciously participated in this study as part of the first conference on MECP2 duplication syndrome.

References

  1. Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23(2), 185–188. doi: 10.1038/13810.PubMedCrossRefGoogle Scholar
  2. Barger, B. D., Campbell, J. M., & McDonough, J. D. (2012). Prevalence and onset of regression within autism spectrum disorders: A meta-analytic review. Journal of Autism and Developmental Disorders,. doi: 10.1007/s10803-012-1621-x.Google Scholar
  3. Bernabei, P., Cerquiglini, A., Cortesi, F., & D’Ardia, C. (2007). Regression versus no regression in the autistic disorder: Developmental trajectories. Journal of Autism and Developmental Disorders, 37(3), 580–588. doi: 10.1007/s10803-006-0201-3.PubMedCrossRefGoogle Scholar
  4. Bijlsma, E. K., Collins, A., Papa, F. T., Tejada, M. I., Wheeler, P., Peeters, E. A., et al. (2012). Xq28 duplications including MECP2 in five females: Expanding the phenotype to severe mental retardation. European Journal of Medical Genetics, 55(6–7), 404–413. doi: 10.1016/j.ejmg.2012.02.009.PubMedCrossRefGoogle Scholar
  5. Carvalho, C. M., Ramocki, M. B., Pehlivan, D., Franco, L. M., Gonzaga-Jauregui, C., Fang, P., et al. (2011). Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome. Nature Genetics, 43(11), 1074–1081. doi: 10.1038/ng.944.PubMedCrossRefGoogle Scholar
  6. del Gaudio, D., Fang, P., Scaglia, F., Ward, P. A., Craigen, W. J., Glaze, D. G., et al. (2006). Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males. Genetic Medicine, 8(12), 784–792. doi: 10.1097/01.gim.0000250502.28516.3c.CrossRefGoogle Scholar
  7. Djukic, A., Valicenti McDermott, M., Mavrommatis, K., & Martins, C. L. (2012). Rett syndrome: Basic features of visual processing-a pilot study of eye-tracking. Pediatric Neurology, 47(1), 25–29. doi: 10.1016/j.pediatrneurol.2012.04.009.PubMedCrossRefGoogle Scholar
  8. Friez, M. J., Jones, J. R., Clarkson, K., Lubs, H., Abuelo, D., Bier, J. A., et al. (2006). Recurrent infections, hypotonia, and mental retardation caused by duplication of MECP2 and adjacent region in Xq28. Pediatrics, 118(6), e1687–e1695. doi: 10.1542/peds.2006-0395.PubMedCrossRefGoogle Scholar
  9. 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(4), 613–627. doi: 10.1007/s10803-006-0280-1.PubMedCrossRefGoogle Scholar
  10. Grasshoff, U., Bonin, M., Goehring, I., Ekici, A., Dufke, A., Cremer, K., et al. (2011). De novo MECP2 duplication in two females with random X-inactivation and moderate mental retardation. European Journal of Human Genetics, 19(5), 507–512. doi: 10.1038/ejhg.2010.226.PubMedCrossRefGoogle Scholar
  11. Jones, L. A., & Campbell, J. M. (2010). Clinical characteristics associated with language regression for children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 40(1), 54–62. doi: 10.1007/s10803-009-0823-3.PubMedCrossRefGoogle Scholar
  12. Lupski, J. R. (2009). Genomic disorders ten years on. Genetic Medicine, 1(4), 42. doi: 10.1186/gm42.Google Scholar
  13. Luyster, R., Richler, J., Risi, S., Hsu, W. L., Dawson, G., Bernier, R., et al. (2005). Early regression in social communication in autism spectrum disorders: A CPEA Study. Development Neuropsychology, 27(3), 311–336. doi: 10.1207/s15326942dn2703_2.CrossRefGoogle Scholar
  14. Neul, J. L., Kaufmann, W. E., Glaze, D. G., Christodoulou, J., Clarke, A. J., Bahi-Buisson, N., et al. (2010). Rett syndrome: Revised diagnostic criteria and nomenclature. Annals Neurology, 68(6), 944–950. doi: 10.1002/ana.22124.CrossRefGoogle Scholar
  15. Ozonoff, S., Heung, K., Byrd, R., Hansen, R., & Hertz-Picciotto, I. (2008). The onset of autism: Patterns of symptom emergence in the first years of life. Autism Research, 1(6), 320–328. doi: 10.1002/aur.53.PubMedCrossRefGoogle Scholar
  16. Ozonoff, S., Iosif, A. M., Young, G. S., Hepburn, S., Thompson, M., Colombi, C. et al. (2011). Onset patterns in autism: correspondence between home video and parent report. Journal of American Academy of Child and Adolescent Psychiatry, 50(8), 796–806 e791. doi: 10.1016/j.jaac.2011.03.012.Google Scholar
  17. Parr, J. R., Le Couteur, A., Baird, G., Rutter, M., Pickles, A., Fombonne, E., et al. (2011). Early developmental regression in autism spectrum disorder: Evidence from an international multiplex sample. Journal of Autism and Developmental Disorders, 41(3), 332–340. doi: 10.1007/s10803-010-1055-2.PubMedCrossRefGoogle Scholar
  18. Peters, S. U., Hundley, R. J., Wilson, A. K., Warren, Z., Vehorn, A., Carvalho, C. M. B., et al. (2013). The behavioral phenotype in MECP2 duplication syndrome: A comparison with idiopathic autism. Autism Research, 6, 42–50.PubMedCrossRefGoogle Scholar
  19. Ramocki, M. B., Peters, S. U., Tavyev, Y. J., Zhang, F., Carvalho, C. M., Schaaf, C. P., et al. (2009). Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome. Annals Neurology, 66(6), 771–782. doi: 10.1002/ana.21715.CrossRefGoogle Scholar
  20. Richler, J., Luyster, R., Risi, S., Hsu, W. L., Dawson, G., Bernier, R., et al. (2006). Is there a ‘regressive phenotype’ of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA study. Journal of Autism and Developmental Disorders, 36(3), 299–316. doi: 10.1007/s10803-005-0070-1.PubMedCrossRefGoogle Scholar
  21. Van Esch, H. (2012). MECP2 duplication syndrome. Molecular Syndromology, 2(3–5), 128–136. doi: 10.1159/000329580.PubMedGoogle Scholar
  22. Vignoli, A., Borgatti, R., Peron, A., Zucca, C., Ballarati, L., Bonaglia, C., et al. (2012). Electroclinical pattern in MECP2 duplication syndrome: Eight new reported cases and review of literature. Epilepsia, 53(7), 1146–1155. doi: 10.1111/j.1528-1167.2012.03501.x.PubMedCrossRefGoogle Scholar
  23. Yang, T., Ramocki, M. B., Neul, J. L., Lu, W., Roberts, L., Knight, J., et al. (2012). Overexpression of methyl-CpG binding protein 2 impairs TH1 responses. Science Translational Medicine, 4(163), 163ra158. doi: 10.1126/scitranslmed.3004430.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • S. U. Peters
    • 1
    • 2
  • R. J. Hundley
    • 1
    • 2
  • A. K. Wilson
    • 2
  • C. M. B. Carvalho
    • 3
  • J. R. Lupski
    • 3
  • M. B. Ramocki
    • 4
  1. 1.Departments of Pediatrics and PsychiatryVanderbilt UniversityNashvilleUSA
  2. 2.Vanderbilt Kennedy Center for Research on Human DevelopmentNashvilleUSA
  3. 3.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  4. 4.Department of Pediatrics, Section of Pediatric Neurology and Developmental NeuroscienceBaylor College of MedicineHoustonUSA

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