Academic Learning Profiles Across Disorders of KMT2 Gene Family: Superimposed and Distinct Features Across Kabuki, Wiedemann-Steiner and ODLURO Syndromes.
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| Název: | Academic Learning Profiles Across Disorders of KMT2 Gene Family: Superimposed and Distinct Features Across Kabuki, Wiedemann-Steiner and ODLURO Syndromes. |
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| Autoři: | Ng R; Kennedy Krieger Institute, Baltimore, Maryland, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Meier L; Kennedy Krieger Institute, Baltimore, Maryland, USA., O'Donnell-Luria A; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Harris J; Kennedy Krieger Institute, Baltimore, Maryland, USA.; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. |
| Zdroj: | Journal of intellectual disability research : JIDR [J Intellect Disabil Res] 2025 Nov; Vol. 69 (11), pp. 1295-1303. Date of Electronic Publication: 2025 Aug 05. |
| Způsob vydávání: | Journal Article |
| Jazyk: | English |
| Informace o časopise: | Publisher: Blackwell Scientific Publications on behalf of the Royal Society for Mentally Handicapped Children and Adults Country of Publication: England NLM ID: 9206090 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2788 (Electronic) Linking ISSN: 09642633 NLM ISO Abbreviation: J Intellect Disabil Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, UK : Blackwell Scientific Publications on behalf of the Royal Society for Mentally Handicapped Children and Adults, 1992- |
| Výrazy ze slovníku MeSH: | Hematologic Diseases*/genetics , Hematologic Diseases*/physiopathology , Hematologic Diseases*/complications , Abnormalities, Multiple*/physiopathology , Abnormalities, Multiple*/genetics , Vestibular Diseases*/physiopathology , Vestibular Diseases*/genetics , Vestibular Diseases*/complications , Intellectual Disability*/physiopathology , Intellectual Disability*/genetics , Face*/abnormalities , Face*/physiopathology , Learning Disabilities*/physiopathology , Learning Disabilities*/genetics , Learning Disabilities*/etiology , Histone-Lysine N-Methyltransferase*/genetics, Humans ; Child ; Male ; Female ; Adolescent ; Myeloid-Lymphoid Leukemia Protein/genetics |
| Abstrakt: | Objectives: Kabuki syndrome (KS), Wiedemann-Steiner syndrome (WSS) and O'Donnell-Luria-Rodan (ODLURO) syndrome are rare disorders caused by pathogenic variants in histone lysine methyltransferases, specifically the KMT2 gene family. All of these disorders are commonly associated with intellectual disability. Recent studies found overlap between KS and WSS cognitive phenotypes, suggesting shared disease pathogenesis. In contrast, the neuropsychological profile of ODLURO remains largely unknown. This study examines the academic learning concerns across the syndromes to better understand their cognitive profiles and provide guidance for clinical care. Methods: Fifty caregivers participated in this study, 25 with a child with WSS (Mean age = 12.85 years, SD = 1.82), 14 with KS (Mean age = 12.06, SD = 5.91) and 11 with ODLURO (Mean age = 12.43, SD = 4.69). All caregivers completed the Colorado Learning Difficulties Questionnaire, a parent-screening inventory of learning/academic challenges, specifically in reading, math and spatial skills. Results: Results suggest shared deficits in spatial skills, but different patterns of academic learning concerns across syndromes. Those with WSS were rated to show unique challenges in math and spatial domains, while those with ODLURO show global difficulties across areas. Individuals with KS were rated to show the most significant challenges in spatial skills, but comparable reading and math concerns. Conclusions: Study results support recent publications on the overlapping cognitive profile in WSS and KS, specifically with distinct deficits in visual spatial processing. In contrast, ODLURO is associated with more generalised cognitive difficulties that warrant further investigation. Disruption of KMT2 genes may have common and individual effects on neurodevelopment that necessitate cross-syndrome research to illuminate gene-brain-behaviour relationships. (© 2025 MENCAP and John Wiley & Sons Ltd.) |
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| Grant Information: | K23HD101646 National Institute of Child Health and Human Development; Kabuki Syndrome Foundation; Wiedemann-Steiner Syndrome Foundation; KAT6 Foundation; Manton Center for Orphan Disease Research at Boston Children's Hospital; Rubinstein-Taybi Syndrome Children's Foundation; Sekel-Bredenstein Fund |
| Contributed Indexing: | Keywords: KMT2A; KMT2D; KMT2E; academic skills; cognitive behaviour; epigenetics; genetics; histone methyltransferase; intellectual disability; learning disability |
| Substance Nomenclature: | EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) |
| SCR Disease Name: | Kabuki syndrome |
| Entry Date(s): | Date Created: 20250805 Date Completed: 20251031 Latest Revision: 20251031 |
| Update Code: | 20251031 |
| DOI: | 10.1111/jir.70017 |
| PMID: | 40762104 |
| Databáze: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Objectives: Kabuki syndrome (KS), Wiedemann-Steiner syndrome (WSS) and O'Donnell-Luria-Rodan (ODLURO) syndrome are rare disorders caused by pathogenic variants in histone lysine methyltransferases, specifically the KMT2 gene family. All of these disorders are commonly associated with intellectual disability. Recent studies found overlap between KS and WSS cognitive phenotypes, suggesting shared disease pathogenesis. In contrast, the neuropsychological profile of ODLURO remains largely unknown. This study examines the academic learning concerns across the syndromes to better understand their cognitive profiles and provide guidance for clinical care.<br />Methods: Fifty caregivers participated in this study, 25 with a child with WSS (Mean age = 12.85 years, SD = 1.82), 14 with KS (Mean age = 12.06, SD = 5.91) and 11 with ODLURO (Mean age = 12.43, SD = 4.69). All caregivers completed the Colorado Learning Difficulties Questionnaire, a parent-screening inventory of learning/academic challenges, specifically in reading, math and spatial skills.<br />Results: Results suggest shared deficits in spatial skills, but different patterns of academic learning concerns across syndromes. Those with WSS were rated to show unique challenges in math and spatial domains, while those with ODLURO show global difficulties across areas. Individuals with KS were rated to show the most significant challenges in spatial skills, but comparable reading and math concerns.<br />Conclusions: Study results support recent publications on the overlapping cognitive profile in WSS and KS, specifically with distinct deficits in visual spatial processing. In contrast, ODLURO is associated with more generalised cognitive difficulties that warrant further investigation. Disruption of KMT2 genes may have common and individual effects on neurodevelopment that necessitate cross-syndrome research to illuminate gene-brain-behaviour relationships.<br /> (© 2025 MENCAP and John Wiley & Sons Ltd.) |
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| ISSN: | 1365-2788 |
| DOI: | 10.1111/jir.70017 |