WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome

Clin Genet. 2018 Feb;93(2):360-364. doi: 10.1111/cge.13054. Epub 2017 Sep 7.


The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.

Keywords: WDR45B; epilepsy; intellectual disability; quadriplegia; spasticity.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Child
  • Child, Preschool
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Homozygote
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Mutation
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / pathology
  • Quadriplegia / genetics
  • Quadriplegia / pathology


  • Adaptor Proteins, Signal Transducing
  • WDR45B protein, human