Research Themes in KAT6A Syndrome: A Scoping Review
Pathogenic variants in the <i>KAT6A</i> gene cause KAT6A syndrome, a neurodevelopmental disorder characterised by intellectual disability (ID), developmental delay, speech and language challenges, feeding difficulties, and skeletal abnormalities. This scoping review synthesises current k...
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2025-04-01
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| author | Tanya Tripathi Miya St John Jordan Wright Natacha Esber David J. Amor |
| author_facet | Tanya Tripathi Miya St John Jordan Wright Natacha Esber David J. Amor |
| author_sort | Tanya Tripathi |
| collection | DOAJ |
| description | Pathogenic variants in the <i>KAT6A</i> gene cause KAT6A syndrome, a neurodevelopmental disorder characterised by intellectual disability (ID), developmental delay, speech and language challenges, feeding difficulties, and skeletal abnormalities. This scoping review synthesises current knowledge on KAT6A syndrome, identifies key research themes, and supports the mission of advocacy groups like the KAT6 Foundation. A systematic search of five databases (Ovid MEDLINE, Ovid EMBASE, PubMed, Web of Science, and Scopus) was conducted from 1990 to 2024, including peer-reviewed articles, preprints, and conference abstracts published from 2022 onward. Of 771 citations retrieved, 111 full-text articles were reviewed, with 62 meeting the inclusion criteria. Data were synthesised into six themes: (1) the genotype and phenotype map, revealing a broad phenotypic spectrum with common features like ID, absent speech, and craniofacial dysmorphism, as well as rare features such as severe aplastic anaemia and pancraniosynostosis; (2) the neurodevelopmental profile, detailing communication deficits, sleep disturbances, and impaired adaptive functioning; (3) the epigenetic and developmental roles of <i>KAT6A</i>, highlighting its critical function in histone acetylation, chromatin remodelling, and gene regulation; (4) molecular biomarkers, identifying distinct DNA methylation episignatures and dysregulated cellular pathways; (5) drug discovery, with preliminary studies suggesting that pantothenate and L-carnitine may mitigate mitochondrial dysfunction and histone acetylation deficits, while RSPO2 overexpression reverses cognitive impairment in animal models; (6) phenotypic overlap with Rett syndrome and <i>KAT6B</i>-related disorders. This review underscores the complexity and variability of KAT6A syndrome, highlighting the need for multidisciplinary approaches to improving diagnosis, management, and development of therapies. Future research should focus on longitudinal studies, underrepresented phenotypes, biomarker identification, and robust therapeutic trials to enhance outcomes for affected individuals and their families. |
| format | Article |
| id | doaj-art-fd425006a5854f00a55bd3c6f7feca47 |
| institution | Kabale University |
| issn | 2673-8856 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | DNA |
| spelling | doaj-art-fd425006a5854f00a55bd3c6f7feca472025-08-20T03:27:18ZengMDPI AGDNA2673-88562025-04-01522110.3390/dna5020021Research Themes in KAT6A Syndrome: A Scoping ReviewTanya Tripathi0Miya St John1Jordan Wright2Natacha Esber3David J. Amor4Murdoch Children’s Research Institute, Parkville 3052, AustraliaMurdoch Children’s Research Institute, Parkville 3052, AustraliaMurdoch Children’s Research Institute, Parkville 3052, AustraliaKAT6 Foundation, 3 Louise Drive, West Nyack, NY 10994, USAMurdoch Children’s Research Institute, Parkville 3052, AustraliaPathogenic variants in the <i>KAT6A</i> gene cause KAT6A syndrome, a neurodevelopmental disorder characterised by intellectual disability (ID), developmental delay, speech and language challenges, feeding difficulties, and skeletal abnormalities. This scoping review synthesises current knowledge on KAT6A syndrome, identifies key research themes, and supports the mission of advocacy groups like the KAT6 Foundation. A systematic search of five databases (Ovid MEDLINE, Ovid EMBASE, PubMed, Web of Science, and Scopus) was conducted from 1990 to 2024, including peer-reviewed articles, preprints, and conference abstracts published from 2022 onward. Of 771 citations retrieved, 111 full-text articles were reviewed, with 62 meeting the inclusion criteria. Data were synthesised into six themes: (1) the genotype and phenotype map, revealing a broad phenotypic spectrum with common features like ID, absent speech, and craniofacial dysmorphism, as well as rare features such as severe aplastic anaemia and pancraniosynostosis; (2) the neurodevelopmental profile, detailing communication deficits, sleep disturbances, and impaired adaptive functioning; (3) the epigenetic and developmental roles of <i>KAT6A</i>, highlighting its critical function in histone acetylation, chromatin remodelling, and gene regulation; (4) molecular biomarkers, identifying distinct DNA methylation episignatures and dysregulated cellular pathways; (5) drug discovery, with preliminary studies suggesting that pantothenate and L-carnitine may mitigate mitochondrial dysfunction and histone acetylation deficits, while RSPO2 overexpression reverses cognitive impairment in animal models; (6) phenotypic overlap with Rett syndrome and <i>KAT6B</i>-related disorders. This review underscores the complexity and variability of KAT6A syndrome, highlighting the need for multidisciplinary approaches to improving diagnosis, management, and development of therapies. Future research should focus on longitudinal studies, underrepresented phenotypes, biomarker identification, and robust therapeutic trials to enhance outcomes for affected individuals and their families.https://www.mdpi.com/2673-8856/5/2/21KAT6A syndromeintellectual disabilitysyndromic disordersspeech and language challenges and phenotypic variability |
| spellingShingle | Tanya Tripathi Miya St John Jordan Wright Natacha Esber David J. Amor Research Themes in KAT6A Syndrome: A Scoping Review DNA KAT6A syndrome intellectual disability syndromic disorders speech and language challenges and phenotypic variability |
| title | Research Themes in KAT6A Syndrome: A Scoping Review |
| title_full | Research Themes in KAT6A Syndrome: A Scoping Review |
| title_fullStr | Research Themes in KAT6A Syndrome: A Scoping Review |
| title_full_unstemmed | Research Themes in KAT6A Syndrome: A Scoping Review |
| title_short | Research Themes in KAT6A Syndrome: A Scoping Review |
| title_sort | research themes in kat6a syndrome a scoping review |
| topic | KAT6A syndrome intellectual disability syndromic disorders speech and language challenges and phenotypic variability |
| url | https://www.mdpi.com/2673-8856/5/2/21 |
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