Anatomical and functional abnormalities on MRI in kabuki syndrome
Open accessAbstract
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.
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For some of these monogenic syndromes it has recently been shown that deficits in the structural development of the PFC underlie these problems.
“For some of these syndromes it has recently been shown that deficits in the structural development of the PFC underlie these problems [281–287].”
From Development of prefrontal cortex (2022) · cites this paper as [283]
The Discussion (page unavailable) reports reduced grey matter in a prefrontal region in patients with Kabuki syndrome and says frontal abnormalities may explain some motor impairments. The Conclusion (page unavailable) likewise describes a possible brain substrate for fine-motor deficits. The study does not establish that disrupted PFC development underlies those problems; it presents the link as a possibility. (LLM, conf=0.86)
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- Authors
- Boisgontier, J., Tacchella, J. M., Lemaître, H., Lehman, N., Saitovitch, A., Gatinois, V., Boursier, G., Sanchez, E., Rechtman, E., Fillon, L., Lyonnet, S., Le Quang Sang, K.-H., Baujat, G., Rio, M., Boute, O., Faivre, L., Schaefer, E., Sanlaville, D., Zilbovicius, M., Grévent, D., Geneviève, D., & Boddaert, N.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Université Paris-Sud (FR)
- Inserm (FR)
- Hôpital Jeanne de Flandre (FR)
- CHU Dijon Bourgogne (FR)
- Lyon 1 Université (FR)
- Corresponding author
- Boisgontier, Jennifer
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2019
- Volume
- 21
- Pages
- 101610
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC6413468
- OpenAlex
- W2900655515
- Cited by
- 29
- References
- 25
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 3 · 2021: 8 · 2020: 5 · 2019: 5
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion)
- Funders
- Ministère des Affaires Sociales et de la Santé (AOM 07-090)
- Fondation Maladies Rares
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- Kabuki syndrome, KMT2D mutation, KDM6A, brain abnormalities, gray matter volume, cerebral blood flow, precentral gyrus, middle frontal gyrus, hippocampus, dentate gyrus, intellectual disability, fine motor impairment, imaging genetics
- MeSH terms
- Abnormalities, Multiple, Adolescent, Brain, Brain Mapping, Child, Face, Female, Hematologic Diseases, Humans, Magnetic Resonance Imaging, Male, Spin Labels, Vestibular Diseases
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