1. Anatomical and functional abnormalities on MRI in kabuki syndrome
- Author
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Ana Saitovitch, Jennifer Boisgontier, Elza Rechtman, Ludovic Fillon, David Grevent, Odile Boute, Elise Schaefer, Elodie Sanchez, Damien Sanlaville, Natacha Lehman, Laurence Faivre, David Geneviève, Vincent Gatinois, Nathalie Boddaert, Jean Marc Tacchella, Kim-Hanh Le Quang Sang, Marlène Rio, M. Zilbovicius, Hervé Lemaitre, Stanislas Lyonnet, Guilaine Boursier, Geneviève Baujat, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Jeanne de Flandre [Lille], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Part of this work was supported by the French Ministry of Health(ProgrammeHospitalierdeRechercheCliniquenationalAOM07-090),Fondation Maladies Rares, and the French Kabuki Associationhttp://www.syndromekabuki.fr/.WethanktheFrenchKabukiAssociationfortheirhelpinthisstudy., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Michel-Avella, Amandine
- Subjects
Male ,Pathology ,BA, brodmann area ,Arterial spin labeling ,Hippocampus ,lcsh:RC346-429 ,0302 clinical medicine ,GLM, general linear model ,Congenital disorder ,Medicine ,FWHM, full-width at half-maximum ,Child ,TE, echo time ,Brain Mapping ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,SMA, supplementary motor area ,05 social sciences ,DG, dentate gyrus ,Brain ,VCI, verbal comprehension index ,ASL, arterial spin labeling ,Magnetic Resonance Imaging ,TR, repetition time ,PSI, processing speed index ,medicine.anatomical_structure ,Neurology ,Cerebral blood flow ,Vestibular Diseases ,lcsh:R858-859.7 ,Female ,CBF, cerebral blood flow ,medicine.medical_specialty ,Adolescent ,Cognitive Neuroscience ,MNI, Montreal Neurological Institute ,Brodmann area 6 and 9 ,Grey matter ,lcsh:Computer applications to medicine. Medical informatics ,050105 experimental psychology ,Article ,03 medical and health sciences ,VBM, voxel-based morphometry ,Middle frontal gyrus ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Abnormalities, Multiple ,lcsh:Neurology. Diseases of the nervous system ,PRI, perceptive reasoning index ,KS, kabuki syndrome ,Kabuki syndrome ,business.industry ,Dentate gyrus ,Precentral gyrus ,Voxel-based morphometry ,GM, grey matter ,WMI, working memory index ,medicine.disease ,Hematologic Diseases ,Face ,TPM, tissue probability map ,Spin Labels ,Neurology (clinical) ,FSIQ, full-scale intelligence quotient ,business ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - 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., Highlights • Kabuki syndrome children show decreased grey matter in precentral and frontal areas • Decreased rest cerebral blood flow is also observed in the same regions • Hippocampus and dentate gyrus volumes are reduced • Brain abnormalities, so far understudied, could underpin clinical deficits
- Published
- 2019