Journal of Autism and Developmental Disorders

, Volume 45, Issue 6, pp 1649–1657 | Cite as

Autism Spectrum Disorder Profile in Neurofibromatosis Type I

  • Shruti Garg
  • Ellen Plasschaert
  • Mie-Jef Descheemaeker
  • Susan Huson
  • Martine Borghgraef
  • Annick Vogels
  • D. Gareth Evans
  • Eric Legius
  • Jonathan Green
Original Paper

Abstract

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21–40 %. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study characterized the phenotypic profile of ASD symptomatology presenting in 4–16 year old children with NF1 (n = 36) using evidence from parent-rated Social Responsiveness Scale and researcher autism diagnostic observation Scale-2. Compared to IQ-matched reference groups of children with autism and ASD, the NF1 profile shows overall similarity but improved eye contact, less repetitive behaviors and better language skills.

Keywords

NF1 ASD Neurofibromatosis Type 1 Autism spectrum disorder SRS ADOS 

References

  1. Abrahams, B. S., & Geschwind, D. H. (2008). Advances in autism genetics: On the threshold of a new neurobiology [Research support, N.I.H., extramural research support, Non-U.S. gov’t review]. Nature Reviews Genetics, 9(5), 341–355. doi:10.1038/nrg2346.CrossRefPubMedCentralPubMedGoogle Scholar
  2. Acosta, M., Kardel, P., Walsh, K., Rosenbaum, K., Gioia, G., & Packer, R. (2011). Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: Phase 1 study. Pediatric Neurology, 45, 241–245.CrossRefPubMedGoogle Scholar
  3. Adviento, B., Corbin, I. L., Widjaja, F., Desachy, G., Enrique, N., Rosser, T., et al. (2014). Autism traits in the RASopathies. Journal of Medical Genetics, 51(1), 10–20. doi:10.1136/jmedgenet-2013-101951jmedgenet-2013-101951.CrossRefPubMedCentralPubMedGoogle Scholar
  4. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.CrossRefGoogle Scholar
  5. Baird, G., Simonoff, E., Pickles, A., Chandler, S., Loucas, T., Meldrum, D., et al. (2006). Prevalence of disorders of the autism spectrum in a population cohort of children in south thames: The special needs and autism project (SNAP). The Lancet, 15(9531), 210–215.CrossRefGoogle Scholar
  6. Barton, B., & North, K. (2004). Social skills of children with neurofibromatosis type 1. Developmental Medicine and Child Neurology, 46, 553–563.CrossRefPubMedGoogle Scholar
  7. Bruining, H., Eijkemans, M. J., Kas, M. J., Curran, S. R., Vorstman, J. A., & Bolton, P. F. (2014). Behavioral signatures related to genetic disorders in autism. Molecular Autism, 5(1), 11. doi:10.1186/2040-2392-5-112040-2392-5-11.CrossRefPubMedCentralPubMedGoogle Scholar
  8. Constantino, J., Davis, S., Todd, R., Schindler, M.K., Gross, M., Brophy, S., et al. (2003). Validation of a brief quantitative measure of autistic traits: Comparison of the social responsiveness scale with the autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, 33(4), 427–433.Google Scholar
  9. Coude, F., Mignot, C., Lyonnet, S., & Munnich, A. (2007). Early grade repetition and inattention associated with neurofibromatosis type 1. Journal of Attention Disorders, 11, 101–105.Google Scholar
  10. Costa, R., Federov, N., Kogan, J., Murphy, G., Stern, J., Ohno, M., et al. (2002). Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature, 415, 526–530.CrossRefPubMedGoogle Scholar
  11. Deardorf MA, Clark DM, & Krantz ID (2005). Cornelia de Lange Syndrome. GeneReviewsTM[Internet]. Seattle (WA): University of Washington, Seattle. Google Scholar
  12. Diggs-Andrews, K. A., & Gutmann, D. H. (2013). Modeling cognitive dysfunction in neurofibromatosis-1. Trends in Neurosciences, 36(4), 237–247. doi:10.1016/jtins.2012.12.002S0166-2236(12)00217-2.CrossRefPubMedCentralPubMedGoogle Scholar
  13. Evans, D. G., Howard, E., Giblin, C., Clancy, T., Spencer, H., Huson, S. M., et al. (2010). Birth incidence and prevalence of tumor-prone syndromes: Estimates from a UK family genetic register service. [Research support, Non-U.S. Gov’t]. American Journal of Medical Genetics Part A, 152A(2), 327–332. doi:10.1002/ajmg.a.33139.CrossRefPubMedGoogle Scholar
  14. Fombonne, E., du Mazaubrun, C., Cans, C., & Grandjean, H. (1997). Autism and associated medical disorders in a large French epidemiological sample. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 1561–1569.PubMedGoogle Scholar
  15. Garg, S., Green, J., Leadbitter, K., Emsley, R., Lehtonen, A., Evans, D. G., et al. (2013). Neurofibromatosis type 1 and autism spectrum disorder. Pediatrics, 132(6), e1642–e1648. doi:10.1542/peds.2013-1868peds.2013-1868.CrossRefPubMedGoogle Scholar
  16. Geschwind, D. H. (2011). Genetics of autism spectrum disorders. Trends in Cognitive Sciences, 15(9), 409–416. doi:10.1016/j.tics.2011.07.003S1364-6613(11)00145-8.CrossRefPubMedCentralPubMedGoogle Scholar
  17. Gillberg, C., & Forsell, C. (1984). Childhood psychosis and neurofibromatosis—more than a coincidence? Journal of Autism and Developmental Disorders, 14(1), 1–8.CrossRefPubMedGoogle Scholar
  18. Gotham, K., Pickles, A., & Lord, C. (2012). Trajectories of autism severity in children using standardized ADOS scores. Pediatrics, 130(5), e1278–e1284. doi:10.1542/peds.2011-3668peds.2011-3668.CrossRefPubMedCentralPubMedGoogle Scholar
  19. Huijbregts, S., Jahja, R., De Sonneville, L., De Breij, S., & Swaab-Barneveld, H. (2010). Social information processing in children and adolescents with neurofibromatosis type 1. Developmental Medicine and Child Neurology, 52(7), 620–625.CrossRefPubMedGoogle Scholar
  20. Kallarackal, A. J., Simard, J. M., & Bailey, A. M. (2013). The effect of apamin, a small conductance calcium activated potassium (SK) channel blocker, on a mouse model of neurofibromatosis 1. Behavioural Brain Research, 237, 71–75. doi:10.1016/j.bbr.2012.09.009S0166-4328(12)00595-5.CrossRefPubMedGoogle Scholar
  21. Krab, L., de Goede-Bolder, A., Aarsen, F., Pluijm, S., Bouman, M., van der Geest, J., et al. (2008). Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: A randomized controlled trial. JAMA, 300(3), 287–294.CrossRefPubMedCentralPubMedGoogle Scholar
  22. Lehtonen, A., Howie, E., Trump, D., & Huson, S. M. (2013). Behaviour in children with neurofibromatosis type 1: Cognition, executive function, attention, emotion, and social competence. Developmental Medicine and Child Neurology, 55(2), 111–125. doi:10.1111/j.1469-8749.2012.04399.x.CrossRefPubMedGoogle Scholar
  23. Lord, C., Rutter, M., DiLavore, P. C., Risi, S., Gotham, K., & Bishop, S. L. (2012). Autism diagnostic observation schedule, second edition (ADOS-2) manual (part I): Modules 1-4. Torrance, CA: Western Psychological Services.Google Scholar
  24. Mautner, V. F., Kluwe, L., Friedrich, R. E., Roehl, A. C., Bammert, S., Högel, J., et al. (2010). Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. Journal of Medical Genetics, 47(9), 623–630.CrossRefPubMedGoogle Scholar
  25. Moss, J., Howlin, P., Magiati, I., & Oliver, C. (2012). Characteristics of autism spectrum disorder in Cornelia de Lange syndrome. Journal of Child Psychology and Psychiatry, 53(8), 883–891. doi:10.1111/j.1469-7610.2012.02540.x.CrossRefPubMedGoogle Scholar
  26. Mouridsen, S., Andersen, L., Sörensen, S., Rich, B., & Isager, T. (1992). Neurofibromatosis in infantile autism and other types of childhood psychoses. Acta Paedopsychiatrica: International Journal of Child & Adolescent Psychiatry, 55, 15–18.Google Scholar
  27. National Institutes of Health Consensus Development Conference. (1988). Neurofibromatosis conference statement. Archives of Neurology, 45, 575–578.CrossRefGoogle Scholar
  28. Noll, R., Reiter-Purtill, J., Moore, B., Schorry, E., Lovell, A., Vannatta, K., et al. (2007). Social, emotional, and behavioral functioning of children with NF1. American Journal of Medical Genetics Part A, 143A, 2261–2273.CrossRefPubMedGoogle Scholar
  29. Oliver, C., Berg, K., Moss, J., Arron, K., & Burbidge, C. (2011). Delineation of behavioral phenotypes in genetic syndromes: Characteristics of autism spectrum disorder, affect and hyperactivity. Journal of Autism and Developmental Disorders, 41(8), 1019–1032. doi:10.1007/s10803-010-1125-5.CrossRefPubMedGoogle Scholar
  30. Oliver, C., Horsler, K., Berg, K., Bellamy, G., Dick, K., & Griffiths, E. (2007). Genomic imprinting and the expression of affect in Angelman syndrome: What’s in the smile? Journal of Child Psychology and Psychiatry, 48(6), 571–579. doi:10.1111/j.1469-7610.2007.01736.x.CrossRefPubMedGoogle Scholar
  31. Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., et al. (2014). Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. The American Journal of Human Genetics, 94(5), 677–694. doi:10.1016/j.ajhg.2014.03.018S0002-9297(14)00150-5.CrossRefGoogle Scholar
  32. Plasschaert, E., Descheemaeker, M. J., Van Eylen, L., Noens, I., Steyaert, J., & Legius, E. (2014). Prevalence of autism spectrum disorder symptoms in children with neurofibromatosis type 1. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. doi:10.1002/ajmg.b.32280.
  33. Rogers, S. J., Wehner, D. E., & Hagerman, R. (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 Behavioral Pediatrics, 22(6), 409–417.CrossRefPubMedGoogle Scholar
  34. Rudacille, D. (2011). How many tests does it take to diagnose autism? http://sfari.org/news-and-opinion/news/2011/how-many-tests-does-it-take-to-diagnose-autism. Accessed 9 July 2014.
  35. Simonoff, E., Pickles, A., Charman, T., Chandler, S., Loucas, T., & Baird, G. (2008). Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample. Journal of American Academy of Child & Adolescent Psychiatry, 47(8), 921–929.CrossRefGoogle Scholar
  36. Skuse, D. H. (2007). Rethinking the nature of genetic vulnerability to autistic spectrum disorders. [Research support, N.I.H., extramural research support, Non-U.S. Gov’t]. Trends in Genetics, 23(8), 387–395. doi:10.1016/j.tig.2007.06.003.CrossRefPubMedGoogle Scholar
  37. Tordjman, S., Anderson, G. M., Botbol, M., Toutain, A., Sarda, P., Carlier, M., et al. (2012). Autistic disorder in patients with Williams-Beuren syndrome: A reconsideration of the Williams-Beuren syndrome phenotype. PLoS ONE, 7(3), e30778. doi:10.1371/journal.pone.0030778PONE-D-11-09003.CrossRefPubMedCentralPubMedGoogle Scholar
  38. van der Vaart, T., Plasschaert, E., Rietman, A. B., Renard, M., Oostenbrink, R., Vogels, A., et al. (2013). Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): A randomised, placebo-controlled trial. The Lancet Neurology, 12(11), 1076–1083. doi:10.1016/S1474-4422(13)70227-8S1474-4422(13)70227-8.CrossRefPubMedGoogle Scholar
  39. Walsh, K. S., Velez, J. I., Kardel, P. G., Imas, D. M., Muenke, M., Packer, R. J., et al. (2013). Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1. [Research Support, N.I.H., Extramural]. Developmental Medicine and Child Neurology, 55(2), 131–138. doi:10.1111/dmcn.12038.CrossRefPubMedGoogle Scholar
  40. Wechsler, D. (2004). The Wechsler intelligence scale for children—fourth edition. London: Pearson Assessment.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shruti Garg
    • 1
  • Ellen Plasschaert
    • 2
    • 3
    • 4
  • Mie-Jef Descheemaeker
    • 2
    • 4
  • Susan Huson
    • 5
  • Martine Borghgraef
    • 2
  • Annick Vogels
    • 2
    • 3
  • D. Gareth Evans
    • 5
  • Eric Legius
    • 2
    • 3
  • Jonathan Green
    • 1
  1. 1.Institute of Brain Behaviour and Mental HealthUniversity of ManchesterManchesterUK
  2. 2.Center of Human GeneticsUniversity Hospitals of LeuvenLeuvenBelgium
  3. 3.Department of Human GeneticsUniversity Hospitals of LeuvenLeuvenBelgium
  4. 4.Leuven Autism Research (LAuRes)KU LeuvenLeuvenBelgium
  5. 5.Genomic Medicine, Manchester Academic Health Science Centre, Institute of Human DevelopmentThe University of Manchester, Central Manchester University Hospitals NHS Trust, St Mary’s HospitalManchesterUK

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