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.
References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lupski, J. R. (2009). Genomic disorders ten years on. Genetic Medicine, 1(4), 42. doi:10.1186/gm42.
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.
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.
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.
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.
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.
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.
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.
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.
Van Esch, H. (2012). MECP2 duplication syndrome. Molecular Syndromology, 2(3–5), 128–136. doi:10.1159/000329580.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Peters, S.U., Hundley, R.J., Wilson, A.K. et al. Brief Report: Regression Timing and Associated Features in MECP2 Duplication Syndrome. J Autism Dev Disord 43, 2484–2490 (2013). https://doi.org/10.1007/s10803-013-1796-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10803-013-1796-9