Molecularly confirmed Kabuki (Niikawa-Kuroki) syndrome patients demonstrate a specific cognitive profile with extensive visuospatial abnormalities

J. Harris, E. M. Mahone, H. T. Bjornsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background: Kabuki (Niikawa-Kuroki) syndrome (KS) is caused by disease-causing variants in either of two components (KMT2D and KDM6A) of the histone methylation machinery. Nearly all individuals with KS have cognitive difficulties, and most have intellectual disability. Recent studies on a mouse model of KS suggest disruption of normal adult neurogenesis in the granule cell layer of the dentate gyrus of the hippocampus. These mutant mice also demonstrate hippocampal memory defects compared with littermates, but this phenotype is rescued postnatally with agents that target the epigenetic machinery. If these findings are relevant to humans with KS, we would expect significant and disproportionate disruption of visuospatial functioning in these individuals. Methods: To test this hypothesis, we have compiled a battery to robustly explore visuospatial function. We prospectively recruited 22 patients with molecularly confirmed KS and 22 IQ-matched patients with intellectual disability. Results: We observed significant deficiencies in visual motor, visual perception and visual motor memory in the KS group compared with the IQ-matched group on several measures. In contrast, language function appeared to be marginally better in the KS group compared with the IQ-matched group in a sentence comprehension task. Conclusions: Together, our data suggest specific disruption of visuospatial function, likely linked to the dentate gyrus, in individuals with KS and provide the groundwork for a novel and specific outcome measure for a clinical trial in a KS population.

Original languageEnglish
Pages (from-to)489-497
Number of pages9
JournalJournal of Intellectual Disability Research
Volume63
Issue number6
DOIs
Publication statusPublished - Jun 2019

Bibliographical note

Publisher Copyright:
© 2019 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd

Other keywords

  • dentate gyrus
  • epigenetics
  • histone machinery
  • intellectual disability
  • KMT2D
  • neurocognitive testing

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