A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Neuron. 2019 Mar 20;101(6):1070-1088. doi: 10.1016/j.neuron.2019.02.041.


Altered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m)RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders.

Keywords: ASDs; ERK; FMRP; FXS; MNK; TSC; mGluRs; mRNA metabolism; mTOR; synaptopathies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder / diagnostic imaging
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / metabolism*
  • Autism Spectrum Disorder / physiopathology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / physiopathology
  • Dendritic Spines
  • Disease Models, Animal
  • Fragile X Syndrome / diagnostic imaging
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Fragile X Syndrome / physiopathology
  • Humans
  • Mice
  • Neuronal Plasticity*
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / metabolism*
  • Signal Transduction
  • Synapses / metabolism*
  • Synaptic Transmission


  • RNA, Messenger