World Journal of Pediatrics

, Volume 5, Issue 3, pp 169–176 | Cite as

Syndromic autism: causes and pathogenetic pathways

  • Arianna Benvenuto
  • Romina Moavero
  • Riccardo Alessandrelli
  • Barbara Manzi
  • Paolo CuratoloEmail author
Review Article



Autism is a severe neurodevelopmental disorder known to have many different etiologies. In the last few years, significant progresses have been made in comprehending the causes of autism and their multiple impacts on the developing brain. This article aims to review the current understanding of the etiologies and the multiple pathogenetic pathways that are likely to lead to the autistic phenotype.

Data sources

The PubMed database was searched with the keywords “autism” and “chromosomal abnormalities”, “metabolic diseases”, “susceptibility loci”.


Genetic syndromes, defined mutations, and metabolic diseases account for less than 20% of autistic patients. Alterations of the neocortical excitatory/inhibitory balance and perturbations of interneurons’ development represent the most probable pathogenetic mechanisms underlying the autistic phenotype in fragile X syndrome and tuberous sclerosis complex. Chromosomal abnormalities and potential candidate genes are strongly implicated in the disruption of neural connections, brain growth and synaptic/dendritic morphology. Metabolic and mitochondrial defects may have toxic effects on the brain cells, causing neuronal loss and altered modulation of neurotransmission systems.


A wide variety of cytogenetic abnormalities have been recently described, particularly in the low functioning individuals with dysmorphic features. Routine metabolic screening studies should be performed in the presence of autistic regression or suggestive clinical findings. As etiologies of autism are progressively discovered, the number of individuals with idiopathic autism will progressively shrink. Studies of genetic and environmentally modulated epigenetic factors are beginning to provide some clues to clarify the complexities of autism pathogenesis. The role of the neuropediatrician will be to understand the neurological basis of autism, and to identify more homogenous subgroups with specific biologic markers.

Key words

autism candidate genes etiologies pathogenetic pathways 


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Copyright information

© Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag GmbH 2009

Authors and Affiliations

  • Arianna Benvenuto
    • 1
  • Romina Moavero
    • 1
  • Riccardo Alessandrelli
    • 1
  • Barbara Manzi
    • 1
  • Paolo Curatolo
    • 1
    Email author
  1. 1.Department of Neuroscience, Pediatric Neurology UnitTor Vergata UniversityRomeItaly

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