Cerebellar heterotopia in an 11-year-old child with KDM6B-related neurodevelopmental disorder: A case report and review of the literature

Am J Med Genet A. 2024 Jun;194(6):e63555. doi: 10.1002/ajmg.a.63555. Epub 2024 Feb 7.


Heterozygous pathogenic variants in KDM6B have recently been associated to a rare neurodevelopmental disorder referred to as "Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities" and characterized by non-pathognomonic facial and body dysmorphisms, a wide range of neurodevelopmental and behavioral disorders and nonspecific neuroradiological findings. KDM6B encodes a histone demethylase, expressed in different tissues during development, which regulates gene expression through the modulation of chromatin accessibility by RNA polymerase. We herein describe a 11-year-old male patient carrying a novel de novo pathogenic variant in KDM6B exhibiting facial dysmorphisms, dysgraphia, behavioral traits relatable to oppositional defiant, autism spectrum, and attention deficit hyperactivity disorders, a single seizure episode, and a neuroimaging finding of a single cerebellar heterotopic nodule, never described to date in this genetic condition. These findings expand the phenotypic spectrum of this syndrome, highlighting the potential role for KDM6B in cerebellar development and providing valuable insights for genetic counseling.

Keywords: KDM6B; cerebellum; heterotopia; histones; neurodevelopment; regulopathies.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cerebellum* / abnormalities
  • Cerebellum* / diagnostic imaging
  • Cerebellum* / pathology
  • Child
  • Humans
  • Jumonji Domain-Containing Histone Demethylases* / genetics
  • Male
  • Mutation / genetics
  • Neurodevelopmental Disorders* / genetics
  • Neurodevelopmental Disorders* / pathology
  • Phenotype


  • Jumonji Domain-Containing Histone Demethylases
  • KDM6B protein, human