Neurodevelopmental Disorders: From Genetics to Functional Pathways

Trends Neurosci. 2020 Aug;43(8):608-621. doi: 10.1016/j.tins.2020.05.004. Epub 2020 Jun 5.


Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of mutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.

Keywords: gene vulnerability; molecular pathways; mutational load; neurodevelopmental disorders; next-generation sequencing.

Publication types

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

MeSH terms

  • Humans
  • Mutation
  • Neurodevelopmental Disorders* / genetics