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Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature
Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, KMT2D (34–76%) or KDM6A (9–13%). Previously, representative neurobehavioral deficits of KS were recapitulated...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582441/ https://www.ncbi.nlm.nih.gov/pubmed/36276984 http://dx.doi.org/10.3389/fgene.2022.1007046 |
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author | Kalinousky, Allison J. Rapp, Tyler Hijazi, Hadia Johnson, Jennifer Bjornsson, Hans Tomas Harris, Jacqueline R. |
author_facet | Kalinousky, Allison J. Rapp, Tyler Hijazi, Hadia Johnson, Jennifer Bjornsson, Hans Tomas Harris, Jacqueline R. |
author_sort | Kalinousky, Allison J. |
collection | PubMed |
description | Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, KMT2D (34–76%) or KDM6A (9–13%). Previously, representative neurobehavioral deficits of KS were recapitulated in a mouse model, emphasizing the role of KMT2D in brain development, specifically in ongoing hippocampal neurogenesis in the granule cell layer of the dentate gyrus. Interestingly, anxiety, a phenotype that has a known association with decreased hippocampal neurogenesis, has been anecdotally reported in individuals with KS. In this study, anxiety and behavior were assessed in a cohort of 60 individuals with molecularly confirmed KS and 25 unaffected biological siblings, via questionnaires (SCARED/GAS-ID and CBCL/ABCL). Participant age ranged from 4 to 43 years old, with 88.3% of participants having a pathogenic variant in KMT2D, and the rest having variants in KDM6A. In addition, data was collected on adaptive function and positive affect/quality of life in participants with KS using appropriate online surveys including ABAS-III and PROMIS Positive Affect. Survey scores were compared within the KS participants across age groups and between KS participants and their unaffected siblings. We found that children with KS have significantly higher anxiety scores and total behavior problem scores than their unaffected siblings (p = 0.0225, p < 0.0001). Moreover, a large proportion of affected individuals (22.2% of children and 60.0% of adults) surpassed the established threshold for anxiety; this may even be an underestimate given many patients are already treated for anxiety. In this sample, anxiety levels did not correlate with level of cognitive or adaptive function in any KS participants, but negatively correlated with positive affect in children with KS (p = 0.0005). These findings indicate that anxiety is a common neurobehavioral feature of KS. Providers should therefore carefully screen individuals with KS for anxiety as well as other behavioral issues in order to allow for prompt intervention. Neurobehavioral anxiety measures may also prove to be important outcome measures for clinical trials in KS. |
format | Online Article Text |
id | pubmed-9582441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95824412022-10-21 Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature Kalinousky, Allison J. Rapp, Tyler Hijazi, Hadia Johnson, Jennifer Bjornsson, Hans Tomas Harris, Jacqueline R. Front Genet Genetics Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, KMT2D (34–76%) or KDM6A (9–13%). Previously, representative neurobehavioral deficits of KS were recapitulated in a mouse model, emphasizing the role of KMT2D in brain development, specifically in ongoing hippocampal neurogenesis in the granule cell layer of the dentate gyrus. Interestingly, anxiety, a phenotype that has a known association with decreased hippocampal neurogenesis, has been anecdotally reported in individuals with KS. In this study, anxiety and behavior were assessed in a cohort of 60 individuals with molecularly confirmed KS and 25 unaffected biological siblings, via questionnaires (SCARED/GAS-ID and CBCL/ABCL). Participant age ranged from 4 to 43 years old, with 88.3% of participants having a pathogenic variant in KMT2D, and the rest having variants in KDM6A. In addition, data was collected on adaptive function and positive affect/quality of life in participants with KS using appropriate online surveys including ABAS-III and PROMIS Positive Affect. Survey scores were compared within the KS participants across age groups and between KS participants and their unaffected siblings. We found that children with KS have significantly higher anxiety scores and total behavior problem scores than their unaffected siblings (p = 0.0225, p < 0.0001). Moreover, a large proportion of affected individuals (22.2% of children and 60.0% of adults) surpassed the established threshold for anxiety; this may even be an underestimate given many patients are already treated for anxiety. In this sample, anxiety levels did not correlate with level of cognitive or adaptive function in any KS participants, but negatively correlated with positive affect in children with KS (p = 0.0005). These findings indicate that anxiety is a common neurobehavioral feature of KS. Providers should therefore carefully screen individuals with KS for anxiety as well as other behavioral issues in order to allow for prompt intervention. Neurobehavioral anxiety measures may also prove to be important outcome measures for clinical trials in KS. Frontiers Media S.A. 2022-10-06 /pmc/articles/PMC9582441/ /pubmed/36276984 http://dx.doi.org/10.3389/fgene.2022.1007046 Text en Copyright © 2022 Kalinousky, Rapp, Hijazi, Johnson, Bjornsson and Harris. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Kalinousky, Allison J. Rapp, Tyler Hijazi, Hadia Johnson, Jennifer Bjornsson, Hans Tomas Harris, Jacqueline R. Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature |
title | Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature |
title_full | Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature |
title_fullStr | Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature |
title_full_unstemmed | Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature |
title_short | Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature |
title_sort | neurobehavioral phenotype of kabuki syndrome: anxiety is a common feature |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582441/ https://www.ncbi.nlm.nih.gov/pubmed/36276984 http://dx.doi.org/10.3389/fgene.2022.1007046 |
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