Clinical and Molecular Aspects of the Neurodevelopmental Disorder Associated with PAK3 Perturbation

J Mol Neurosci. 2021 Dec;71(12):2474-2481. doi: 10.1007/s12031-021-01868-w. Epub 2021 Jul 5.


X-linked intellectual disability can be diagnosed in about 10-12% of intellectually disabled males. In the past, mutations affecting the PAK3 gene (p21 protein-activated kinase 3, MIM#300142) have been associated with a non-syndromic form of X-linked intellectual disability, which has to date been identified in a limited number of families.Since this neurodevelopmental disorder mostly afflicts males, descriptions of symptomatic female carriers are quite rare.We describe a female patient with neurodevelopmental delay and a novel PAK3 variant. Interestingly, she manifests craniofacial anomalies, including microcephaly, representing the second reported microcephalic female but the first for whom a detailed clinical description is available. She also displays other uncommon clinical findings, which we illustrate.Moreover, a comprehensive clinical and molecular review of all to date published patients has been made. This study contributes to further delineate the PAK3-related phenotype, which can be considered a non-syndromic X-linked intellectual disability, with seemingly recurrent craniofacial abnormalities.

Keywords: Craniofacial dysmorphisms; Microcephaly; Neurodevelopmental delay; PAK3.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Female
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Microcephaly / genetics*
  • Microcephaly / pathology
  • Mutation
  • Phenotype*
  • p21-Activated Kinases / genetics*
  • p21-Activated Kinases / metabolism


  • PAK3 protein, human
  • p21-Activated Kinases