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Molecularly confirmed Kabuki (Niikawa-Kuroki) syndrome patients demonstrate a specific cognitive profile with extensive visuospatial abnormalities.
- Source :
-
Journal of intellectual disability research : JIDR [J Intellect Disabil Res] 2019 Jun; Vol. 63 (6), pp. 489-497. Date of Electronic Publication: 2019 Feb 14. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.<br /> (© 2019 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)
- Subjects :
- Adolescent
Adult
Child
Cognitive Dysfunction etiology
Dentate Gyrus physiopathology
Face physiopathology
Female
Hematologic Diseases complications
Humans
Intellectual Disability etiology
Male
Prospective Studies
Vestibular Diseases complications
Young Adult
Abnormalities, Multiple genetics
Abnormalities, Multiple physiopathology
Cognitive Dysfunction physiopathology
Executive Function physiology
Face abnormalities
Hematologic Diseases genetics
Hematologic Diseases physiopathology
Intellectual Disability physiopathology
Psychomotor Performance physiology
Space Perception physiology
Vestibular Diseases genetics
Vestibular Diseases physiopathology
Visual Perception physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2788
- Volume :
- 63
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of intellectual disability research : JIDR
- Publication Type :
- Academic Journal
- Accession number :
- 30767315
- Full Text :
- https://doi.org/10.1111/jir.12596