Original Article

Molecular Psychiatry (2010) 15, 300–307; doi:10.1038/mp.2008.75; published online 15 July 2008

Minor physical anomalies in autism: a meta-analysis

H M Ozgen1,2, J W Hop1, J J Hox3, F A Beemer4 and H van Engeland1,2

  1. 1Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands
  2. 2Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands
  3. 3Department of Methodology and Statistics, Utrecht, The Netherlands
  4. 4Department of Medical Genetics, University Medical Centre, Utrecht, The Netherlands

Correspondence: Dr HM Ozgen, Department of Child and Adolescent Psychiatry, UMC Utrecht, B01.201, PO Box 85500, 3508 GA, Utrecht, The Netherlands. E-mail: h.m.ozgen@umcutrecht.nl

Received 12 December 2007; Revised 30 May 2008; Accepted 9 June 2008; Published online 15 July 2008.



Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences play a causal role. Despite the compelling evidence for a strong heritability, the etiology and molecular mechanisms underlying autism remain unclear. High phenotypic variability and genetic heterogeneity confounds the identification of susceptibility genes. The lack of robust indicators to tackle this complexity in autism has led researchers to seek for novel diagnostic tools to create homogenous subgroups. Several studies have indicated that patients with autism have higher rates of minor physical anomalies (MPAs) and that MPAs may serve as a diagnostic tool; however, the results have been inconsistent. Using the cumulative data from seven studies on MPAs in autism, this meta-analysis seeks to examine whether the aggregate data provide evidence of a large mean effect size and statistical significance for MPAs in autism. It covers the studies using multiple research methods till June 2007. The current results from seven studies suggested a significant association of MPAs in autism with a robust pooled effect size (d=0.84), and thereby provide the strongest evidence to date about the close association between MPAs and autism. Our results emphasize the importance of MPAs in the identification of heterogeneity in autism and suggest that the success of future autism genetics research will be exploited by the use of MPAs. Implications for the design of future studies on MPAs in autism are discussed and suggestions for further investigation of these important markers are proposed. Clarifying this relation might improve understanding of risk factors and molecular mechanisms in autism.


autistic disorder, heterogeneity, etiology, genotype, phenotype, biological marker



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