Anatomical and functional abnormalities on MRI in kabuki syndrome

Abstract

Kabuki syndrome (KS) is a rare congenital disorder (1/32000 births) characterized by distinctive facial features, intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities. In the last decade, mutations in KMT2D and KDM6A were identified as a major cause of kabuki syndrome. Although genetic abnormalities have been highlighted in KS, brain abnormalities have been little explored. Here, we have investigated brain abnormalities in 6 patients with KS (4 males; Mage = 10.96 years, SD = 2.97 years) with KMT2D mutation in comparison with 26 healthy controls (17 males; Mage = 10.31 years, SD = 2.96 years). We have used MRI to explore anatomical and functional brain abnormalities in patients with KS. Anatomical abnormalities in grey matter volume were assessed by cortical and subcortical analyses. Functional abnormalities were assessed by comparing rest cerebral blood flow measured with arterial spin labeling-MRI. When compared to healthy controls, KS patients had anatomical alterations characterized by grey matter decrease localized in the bilateral precentral gyrus and middle frontal gyrus. In addition, KS patients also presented functional alterations characterized by cerebral blood flow decrease in the left precentral gyrus and middle frontal gyrus. Moreover, subcortical analyses revealed significantly decreased grey matter volume in the bilateral hippocampus and dentate gyrus in patients with KS. Our results strongly indicate anatomical and functional brain abnormalities in KS. They suggest a possible neural basis of the cognitive symptoms observed in KS, such as fine motor impairment, and indicate the need to further explore the consequences of such brain abnormalities in this disorder. Finally, our results encourage further imaging-genetics studies investigating the link between genetics, anatomical and functional brain alterations in KS.

Kabuki syndrome: novel pathogenic variants, new phenotypes and review of literature

“…Cedrik et al reported two patients presented with holoprosencephaly [21]. Furthermore, based on MRI, significantly decreased grey matter volume in the bilateral hippocampus and dentate gyrus have been described in KS patients [22]. We found the brain abnormalities including thinning of pituitary and myelination of cerebral white matter in Chinese KS patients, which were not previously reported in KS patients.…”

Hypoglycemia and Dandy-Walker variant in a Kabuki syndrome patient: a case report

“…Among the major structural brain anomalies in KS patients, Dandy-Walker malformations have been reported in three patients [ 22 , 28 , 29 ]. In addition to major anomalies, based on MRI, Jennifer et al found that the volume of gray matter in the bilateral hippocampus and dentate gyrus in patients with KS was significantly decreased compared those in healthy controls [ 30 ]. MRI of our patient showed cystic enlargement of the fourth ventricle and hypoplasia of the cerebellar vermis, which fulfilled the diagnostic criteria of Dandy-Walker variant.…”

Precocious neuronal differentiation and disrupted oxygen responses in Kabuki syndrome

“…We previously described a mouse model of KS1, Kmt2d +/βgeo [Mll2Gt(RRt024)Byg], demonstrating characteristic features including craniofacial abnormalities and visuospatial memory impairments, associated with decreased adult-born hippocampal NSPCs in the dentate gyrus (DG) (12). Decreased DG gray matter volume was subsequently observed in patients with KS1 (13). The continual birth and integration Chromatin modifiers act to coordinate gene expression changes critical to neuronal differentiation from neural stem/progenitor cells (NSPCs).…”