Skip to main content
Log in

Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity

  • Original paper
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4–51). ASD symptomatology was heightened in CdLS and FXS. High levels of impulsivity were seen in SMS, AS, CdCS, FXS and adults with CdLS. Negative affect was prominent in adults with CdLS, while positive affect was prominent in adults with AS and FXS. Heightened levels of overactivity and impulsivity were identified in FXS, AS and SMS while low levels were identified in PWS. These findings confirm and extend previously reported behavioral phenotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Notes

  1. The n may vary for the analysis due to missing data.

  2. FXS and LS groups excluded from analysis due to the X linked nature of the syndromes and exclusion of females in the FXS group.

References

  • Arron, K., Oliver, C., Berg, K., Moss, J., & Burbidge, C. (in press). Prevalence and phenomenology of self-injurious and aggressive behaviour in genetic syndromes. Journal of Intellectual Disability Research.

  • Barkley, R. A. (1997). Behavioral inhibition. Sustained attention and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121, 65–94.

    Google Scholar 

  • Berney, T. P., Ireland, M., & Burn, J. (1999). Behavioural phenotype of Cornelia de Lange syndrome. Archives of Disease in Childhood, 81, 333–336.

    Article  PubMed  Google Scholar 

  • Berument, S. K., Rutter, M., Lord, C., Pickles, A., & Bailey, A. (1999). Autism screening questionnaire: Diagnostic validity. British Journal of Psychiatry, 175, 444–451.

    Article  PubMed  Google Scholar 

  • Bhuiyan, Z. A., Klein, M., Hammond, P., van Haeringen, A., Mannens, M. M. A. M., Van Berckelaer-Onnes, I., et al. (2006). Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: The Dutch experience. Journal of Medical Genetics, 43, 568–575.

    Article  PubMed  Google Scholar 

  • Boer, H., Holland, A., Whittington, J., Butler, J., Webb, T., & Clarke, D. (2002). Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet, 359, 135–136.

    Article  PubMed  Google Scholar 

  • Burbidge, C., & Oliver, C. (2008). The activity questionnaire. University of Birmingham: Manual for administration and score interpretation.

    Google Scholar 

  • Burbidge, C., Oliver, C., Moss, J., Arron, K., Berg, K., Hill, L., Trusler, K., Furniss, F., & Woodcock, K. A. (in press). The association between repetitive behaviours, impulsivity and hyperactivity in people with intellectual disability. Journal of Intellectual Disability Research.

  • Campbell, L. E., Daly, E., Toal, F., Stevens, A., Azuma, R., Catani, M., et al. (2006). Brain and behaviour in children with 22q11.2 deletion syndrome: A volumetric and voxel-based morphometry MRI study. Brain, 129, 1218–1228.

    Article  PubMed  Google Scholar 

  • Clarke, D., & Marston, G. (2000). Problem behaviors associated with 15q Angelman syndrome. American Journal on Mental Retardation, 105, 25–31.

    Article  PubMed  Google Scholar 

  • Clifford, S., Dissanayake, C., Bui, Q. M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2007). Autism spectrum phenotype in males and females with fragile x full mutation and premutation. Journal of Autism and Developmental Disorders, 37, 738–747.

    Article  PubMed  Google Scholar 

  • Collis, L., Moss, J., Jutley, J., Cornish, K., & Oliver, C. (2008). Facial expression of affect in children with Cornelia de Lange and Cri du Chat syndromes. Journal of Intellectual Disability Research, 52, 207–215.

    Article  PubMed  Google Scholar 

  • Cornish, K. M., Turk, J., Wilding, J., Sudhalter, V., Munir, F., Kooy, F., et al. (2004). Annotation: Deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approach. Journal of Child Psychology and Psychiatry, 45, 1042–1053.

    Article  PubMed  Google Scholar 

  • Cornish, K., Scerif, G., & Karmiloff-Smith, A. (2007). Tracing syndrome-specific trajectories of attention across the lifespan. Cortex, 43, 672–685.

    Article  PubMed  Google Scholar 

  • de Vries, P. J., Hunt, A., & Bolton, P. F. (2007). The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC)—A postal survey of UK families. European Child and Adolescent Psychiatry, 16, 16–24.

    Article  PubMed  Google Scholar 

  • Dykens, E. M. (1995). Measuring behavioral phenotypes: Provocations from the ‘new genetics’. American Journal on Mental Retardation, 99, 522–532.

    PubMed  Google Scholar 

  • Dykens, E. M., & Clarke, D. J. (1997). Correlates of maladaptive behavior in individuals with 5p-(cri du chat) syndrome. Developmental Medicine and Child Neurology, 39, 752–756.

    PubMed  Google Scholar 

  • Dykens, E. M., Hodapp, R. M., & Finucane, B. M. (2000). Genetics and mental retardation syndromes. Baltimore, MD: Paul H Brookes Publishing Co.

    Google Scholar 

  • Dykens, E. M., & Smith, A. C. M. (1998). Distinctiveness and correlates of maladaptive behaviour in children and adolescents with Smith-Magenis syndrome. Journal of Intellectual Disability Research, 42, 481–489.

    Google Scholar 

  • Edelman, E. A., Girirajan, S., Finucane, B., Patel, P. I., Lupski, J. R., Smith, A. C. M., et al. (2007). Gender, genotype, and phenotype differences in Smith-Magenis syndrome: A meta-analysis of 105 cases. Clinical Genetics, 71, 540–550.

    Article  PubMed  Google Scholar 

  • Fine, S. E., Weissman, A., Gerdes, M., Pinto-Martin, J., Zackai, E. H., Donald-McGinn, D. M., et al. (2005). Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. Journal of Autism and Developmental Disorders, 35, 461–470.

    Article  PubMed  Google Scholar 

  • Hall, S., DeBernardis, M., & Reiss, A. (2006). Social escape behaviors in children with fragile X syndrome. Journal of Autism and Developmental Disorders, 36, 935–947.

    Article  PubMed  Google Scholar 

  • Hall, S. S., Burns, D. D., & Reiss, A. L. (2007). Modeling family dynamics in children with fragile X syndrome. Journal of Abnormal Child Psychology, 35, 29–42.

    Article  PubMed  Google Scholar 

  • Hammond, P., Hutton, T. J., Allanson, J. E., Campbell, L. E., Hennekam, R. C., Holden, S., et al. (2004). 3D analysis of facial morphology. American Journal of Medical Genetics, 126, 339–348.

    Article  Google Scholar 

  • Hinton, E. C., Holland, A. J., Gellatly, M. S. N., Soni, S., & Owen, A. M. (2006). An investigation into food preferences and the neural basis of food-related incentive motivation in Prader-Willi syndrome. Journal of Intellectual Disability Research, 50, 633–642.

    Article  PubMed  Google Scholar 

  • Hodapp, R. M., & Dykens, E. (2001). Strengthening behavioral research on genetic mental retardation syndromes. American Journal on Mental Retardation, 106, 4–15.

    Article  PubMed  Google Scholar 

  • Hodapp, R. M., & Dykens, E. M. (2005). Measuring behavior in genetic disorders of mental retardation. Mental Retardation and Developmental Disabilities Research Reviews, 11, 340–346.

    Article  PubMed  Google Scholar 

  • Holland, A. J., Whittington, J. E., Webb, B. T., Boer, H., & Clarke, D. (2003). Behavioural phenotypes associated with specific genetic disorders: Evidence from a population-based study of people with Prader-Willi syndrome. Psychological Medicine, 33, 141–153.

    Article  PubMed  Google Scholar 

  • Horsler, K., & Oliver, C. (2006a). Environmental influences on the behavioral phenotype of Angelman syndrome. American Journal on Mental Retardation, 11, 311–321.

    Article  Google Scholar 

  • Horsler, K., & Oliver, C. (2006b). The behavioural phenotype of Angelman syndrome. Journal of Intellectual Disability Research, 50, 33–53.

    Article  PubMed  Google Scholar 

  • Howlin, P., & Karpf, J. (2004). Using the social communication questionnaire to identify ‘autistic spectrum’ disorders associated with other genetic conditions: Findings from a study of individuals with Cohen syndrome. Autism, 8, 175–182.

    Article  PubMed  Google Scholar 

  • Hyman, P., Oliver, C., & Hall, S. (2002). Self-injurious behavior, self-restraint and compulsive behaviors in Cornelia de Lange syndrome. American Journal on Mental Retardation, 107, 146–154.

    Article  PubMed  Google Scholar 

  • Jarrold, C., & Brock, J. (2004). To match or not to match? Methodological issues in autism-related research. Journal of Autism and Developmental Disorders, 34, 81–86.

    Article  PubMed  Google Scholar 

  • Jarrold, C., Baddeley, A. D., & Phillips, C. E. (2002). Verbal short-term memory in Down syndrome: A problem of memory, audition, or speech? Journal of Speech Language and Hearing Research, 45, 531–544.

    Article  Google Scholar 

  • Jarrold, C., Baddeley, A. D., & Phillips, C. (2007). Long-term memory for verbal and visual information in Down syndrome and Williams syndrome: Performance on the doors and people test. Cortex, 43, 233–247.

    Article  PubMed  Google Scholar 

  • Karmiloff-Smith, A., Thomas, M., Annaz, D., Humphreys, K., Ewing, S., Brace, N., et al. (2004). Exploring the Williams syndrome face-processing debate: The importance of building developmental trajectories. Journal of Child Psychology and Psychiatry, 45, 1258–1274.

    Article  PubMed  Google Scholar 

  • Kline, A. D., Krantz, I. D., Sommer, A., Kleiwer, M., Jackson, L. D., FitzPatrick, D. R., et al. (2007). Cornelia de Lange syndrome: Clinical review, diagnostic and scoring systems, and anticipatory guidance. American Journal of Medical Genetics (Part A), 143A, 1287–1296.

    Article  Google Scholar 

  • Kushlick, A., Blunden, R., & Cox, G. (1973). A method for rating behavior characteristics for use in large scale studies of mental handicap. Psychological Medicine, 3, 466–478.

    Article  PubMed  Google Scholar 

  • Lauterborn, J. C., Rex, C. S., Kramar, E., Chen, L. Y., Pandyarajan, V., Lynch, G., et al. (2007). Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile x syndrome. Journal of Neuroscience, 27, 10685–10694.

    Article  PubMed  Google Scholar 

  • Lord, C., Rutter, M., & Lecouteur, 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.

    Article  PubMed  Google Scholar 

  • Milner, K. M., Craig, E. E., Thompson, R. J., Veltman, M. W. M., Thomas, N. S., Roberts, S., Bellamy, M., Curran, S., Sporikou, C. M. J. & Bolton, P. (2005). Prader-Willi syndrome: intellectual abilities and behavioural features by genetic subtype. Journal of Child Psychology and Psychiatry, 46, 1089–1096.

    Google Scholar 

  • Moore, D. G., Oates, J. M., Hobson, R. P., & Goodwin, J. (2002). Cognitive and social factors in the development of infants with Down syndrome. Down Syndrome Research and Practice, 8, 43–52.

    Article  Google Scholar 

  • Moss, J., Kaur, G., Jephcott, L., Berg, K., Cornish, K., & Oliver, C. (2008). The prevalence and phenomenology of autistic spectrum disorder in Cornelia de Lange and Cri du Chat syndromes. American Journal on Mental Retardation, 113, 278–291.

    Article  PubMed  Google Scholar 

  • Moss, J., Oliver, C., Arron, K., Burbidge, C., & Berg, K. (2009). The prevalence and phenomenology of repetitive behavior in genetic syndromes. Journal of Autism and Developmental Disorders, 39, 572–588.

    Google Scholar 

  • Murphy, K. C. (2005). Annotation: Velo-cardio-facial syndrome. Journal of Child Psychology and Psychiatry, 46, 563–571.

    Article  PubMed  Google Scholar 

  • Nordin, V., & Gillberg, C. (1996). Autism spectrum disorders in children with physical or mental disability or both. II: Screening aspects. Developmental Medicine and Child Neurology, 38, 314–324.

    Article  PubMed  Google Scholar 

  • O’Brien, G., & Yule, W. (1995). Behavioural phenotypes. MacKeith Press: Cambridge.

    Google Scholar 

  • Oliver, C., Arron, K., Hall, S., & Sloneem, J. (2008). The behavioural phenotype of Cornelia de Lange syndrome. British Journal of Psychiatry, 193, 466–470.

    Google Scholar 

  • Oliver, C., Crayton, L., Holland, A. J., Hall, S., & Bradbury, J. (1998). A four year study of age related cognitive and behavioural change in adults with Down’s syndrome. Psychological Medicine, 28, 1365–1377.

    Article  PubMed  Google Scholar 

  • Oliver, C., & Hagerman, R. (2007). Trends and challenges in behavioural phenotype research. Journal of Intellectual Disability Research, 51, 649–652.

    Google Scholar 

  • 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, 571–579.

    Article  PubMed  Google Scholar 

  • Palmer, J., & Jenkins, J. (1982). The ‘Wessex’ behaviour rating system for mentally handicapped people: Reliability study. British Journal of Mental Subnormality, 28, 88–96.

    Google Scholar 

  • Reiss, A. L., & Hall, S. S. (2007). Fragile X syndrome: Assessment and treatment implications. Child and Adolescent Psychiatric Clinics of North America, 16, 663–675.

    Article  PubMed  Google Scholar 

  • Rogers, S. J., Wehner, E. A., & 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, 409–417.

    Article  PubMed  Google Scholar 

  • Ross, E., & Oliver, C. (2003). Preliminary analysis of the psychometric properties of the mood, interest and pleasure questionnaire (MIPQ) for adults with severe and profound learning disabilities. British Journal of Clinical Psychology, 42, 81–93.

    Article  PubMed  Google Scholar 

  • Ross, E., Arron, K. & Oliver, C. (2008). The mood interest and pleasure questionnaire: manual for administration and scoring. University of Birmingham.

  • Scerif, G., Cornish, K., Wilding, J., Driver, J., & Karmiloff-Smith, A. (2007). Delineation of early attentional control difficulties in Fragile X syndrome: Focus on neurocomputational changes. Neuropsychologia, 45, 1889–1898.

    Article  PubMed  Google Scholar 

  • Skuse, D. H., James, R. S., Bishop, D. V. M., Coppin, B., Dalton, P., AamodtLeeper, G., et al. (1997). Evidence from Turner’s syndrome of an imprinted X-linked locus affecting cognitive function. Nature, 387, 705–708.

    Article  PubMed  Google Scholar 

  • Taylor, L., & Oliver, C. (2008). The behavioural phenotype of Smith-Magenis syndrome: Evidence for a gene-environment interaction. Journal of Intellectual Disability Research, 52, 830­-841.

    Google Scholar 

  • Thomas, M. S. C., & Karmiloff-Smith, A. (2005). Can developmental disorders reveal the component parts of the human language faculty? Language Learning and Development, 1, 65–92.

    Article  Google Scholar 

  • Woodcock, K., Oliver, C., & Humphreys, G. W. (2009a). Hypothesis: A specific pathway can be identified between genetic and behaviour profiles in Prader-Willi syndrome via cognitive, environmental and physiological mechanisms. Journal of Intellectual Disability Research, 53, 493–500.

    Google Scholar 

  • Woodcock, K. A., Oliver, C., & Humphreys, G. W. (2009b). Task switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: Data from children with Prader-Willi syndrome chromosome 15 q11–q13 deletion and boys with Fragile-X syndrome. Cognitive Neuropsychology, 26, 172–194.

    Article  PubMed  Google Scholar 

  • Zhang, X. X., Snijders, A., Segraves, R., Zhang, X. Q., Niebuhr, A., Albertson, D., et al. (2005). High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative genomic hybridization. American Journal of Human Genetics, 76, 312–326.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to the Angelman Syndrome Support Education and Research Trust, Cri du Chat Syndrome Support Group, Fragile X Society, Prader-Willi Syndrome Association, Lowe Syndrome Trust UK, Lowe Syndrome Association USA, Smith-Magenis Syndrome Foundation and the Cornelia de Lange Syndrome Foundation (UK and Ireland). Michelle Hooker and Sarah Duffay assisted with data collection.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chris Oliver.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oliver, C., Berg, K., Moss, J. et al. Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity. J Autism Dev Disord 41, 1019–1032 (2011). https://doi.org/10.1007/s10803-010-1125-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-010-1125-5

Keywords

Navigation