Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3)
BackgroundChromatin Modifying Disorders (CMD) have emerged as one of the most rapidly expanding genetic disorders associated with autism spectrum disorders (ASD). Motor impairments are also prevalent in CMD and may play a role in the neurodevelopmental phenotype. Evidence indicates that neurodevelop...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1244176/full |
| _version_ | 1797635668754563072 |
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| author | Maya C. Ayoub Jeffrey T. Anderson Bianca E. Russell Rujuta B. Wilson |
| author_facet | Maya C. Ayoub Jeffrey T. Anderson Bianca E. Russell Rujuta B. Wilson |
| author_sort | Maya C. Ayoub |
| collection | DOAJ |
| description | BackgroundChromatin Modifying Disorders (CMD) have emerged as one of the most rapidly expanding genetic disorders associated with autism spectrum disorders (ASD). Motor impairments are also prevalent in CMD and may play a role in the neurodevelopmental phenotype. Evidence indicates that neurodevelopmental outcomes in CMD may be treatable postnatally; thus deep phenotyping of these conditions can improve clinical screening while improving the development of treatment targets for pharmacology and for clinical trials. Here, we present developmental phenotyping data on individuals with Bohring-Optiz Syndrome (BOS – ASXL1) and Bainbridge-Ropers Syndrome (BRS – ASXL3) related disorders, two CMDs highly penetrant for motor and developmental delays.ObjectivesTo phenotype the motor and neurodevelopmental profile of individuals with ASXL1 and ASXL3 related disorders (BOS and BRS). To provide a preliminary report on the association of motor impairments and ASD.MethodsNeurodevelopmental and motor phenotyping was conducted on eight individuals with pathogenic ASXL1 variants and seven individuals with pathogenic ASXL3 variants, including medical and developmental background intake, movement and development questionnaires, neurological examination, and quantitative gait analysis.ResultsAverage age of first developmental concerns was 4 months for individuals with BOS and 9 months in BRS. 100% of individuals who underwent the development questionnaire met a diagnosis of developmental coordination disorder. 71% of children with BOS and 0% of children with BRS noted movement difficulty greatly affected classroom learning. Participants with BRS and presumed diagnoses of ASD were reported to have more severe motor impairments in recreational activities compared to those without ASD. This was not the case for the individuals with BOS.ConclusionMotor impairments are prevalent and pervasive across the ASXL disorders with and without ASD, and these impairments negatively impact engagement in school-based activities. Unique neurodevelopmental and motor findings in our data include a mixed presentation of hypo and hypertonia in individuals with BOS across a lifespan. Individuals with BRS exhibited hypotonia and greater variability in motor skills. This deep phenotyping can aid in appropriate clinical diagnosis, referral to interventions, and serve as meaningful treatment targets in clinical trials. |
| first_indexed | 2024-03-11T12:24:36Z |
| format | Article |
| id | doaj.art-4f77f8783d88493bb50e12046ebd365c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-11T12:24:36Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-4f77f8783d88493bb50e12046ebd365c2023-11-06T13:05:44ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-11-011710.3389/fnins.2023.12441761244176Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3)Maya C. Ayoub0Jeffrey T. Anderson1Bianca E. Russell2Rujuta B. Wilson3Division of Child Neurology, Department of Pediatrics, UCLA Health, Los Angeles, CA, United StatesDepartment of Medicine, UCLA Health, UCLA David Geffen School of Medicine, Los Angeles, CA, United StatesDivision of Clinical Genetics, Department of Human Genetics, UCLA Health, UCLA David Geffen School of Medicine, Los Angeles, CA, United StatesDivision of Child Psychiatry, Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, UCLA David Geffen School of Medicine, Los Angeles, CA, United StatesBackgroundChromatin Modifying Disorders (CMD) have emerged as one of the most rapidly expanding genetic disorders associated with autism spectrum disorders (ASD). Motor impairments are also prevalent in CMD and may play a role in the neurodevelopmental phenotype. Evidence indicates that neurodevelopmental outcomes in CMD may be treatable postnatally; thus deep phenotyping of these conditions can improve clinical screening while improving the development of treatment targets for pharmacology and for clinical trials. Here, we present developmental phenotyping data on individuals with Bohring-Optiz Syndrome (BOS – ASXL1) and Bainbridge-Ropers Syndrome (BRS – ASXL3) related disorders, two CMDs highly penetrant for motor and developmental delays.ObjectivesTo phenotype the motor and neurodevelopmental profile of individuals with ASXL1 and ASXL3 related disorders (BOS and BRS). To provide a preliminary report on the association of motor impairments and ASD.MethodsNeurodevelopmental and motor phenotyping was conducted on eight individuals with pathogenic ASXL1 variants and seven individuals with pathogenic ASXL3 variants, including medical and developmental background intake, movement and development questionnaires, neurological examination, and quantitative gait analysis.ResultsAverage age of first developmental concerns was 4 months for individuals with BOS and 9 months in BRS. 100% of individuals who underwent the development questionnaire met a diagnosis of developmental coordination disorder. 71% of children with BOS and 0% of children with BRS noted movement difficulty greatly affected classroom learning. Participants with BRS and presumed diagnoses of ASD were reported to have more severe motor impairments in recreational activities compared to those without ASD. This was not the case for the individuals with BOS.ConclusionMotor impairments are prevalent and pervasive across the ASXL disorders with and without ASD, and these impairments negatively impact engagement in school-based activities. Unique neurodevelopmental and motor findings in our data include a mixed presentation of hypo and hypertonia in individuals with BOS across a lifespan. Individuals with BRS exhibited hypotonia and greater variability in motor skills. This deep phenotyping can aid in appropriate clinical diagnosis, referral to interventions, and serve as meaningful treatment targets in clinical trials.https://www.frontiersin.org/articles/10.3389/fnins.2023.1244176/fullBohring-Opitz syndromeASXL1Bainbridge-Ropers syndromeASXL3chromatin modifying disordersautism |
| spellingShingle | Maya C. Ayoub Jeffrey T. Anderson Bianca E. Russell Rujuta B. Wilson Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) Frontiers in Neuroscience Bohring-Opitz syndrome ASXL1 Bainbridge-Ropers syndrome ASXL3 chromatin modifying disorders autism |
| title | Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) |
| title_full | Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) |
| title_fullStr | Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) |
| title_full_unstemmed | Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) |
| title_short | Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) |
| title_sort | examining the neurodevelopmental and motor phenotypes of bohring opitz syndrome asxl1 and bainbridge ropers syndrome asxl3 |
| topic | Bohring-Opitz syndrome ASXL1 Bainbridge-Ropers syndrome ASXL3 chromatin modifying disorders autism |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1244176/full |
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