STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics

BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systemat...

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Autores principales: O’Brien, Sinéad, Ng-Cordell, Elise, Astle, Duncan E., Scerif, Gaia, Baker, Kate
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683428/
https://www.ncbi.nlm.nih.gov/pubmed/31387522
http://dx.doi.org/10.1186/s11689-019-9278-9
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author O’Brien, Sinéad
Ng-Cordell, Elise
Astle, Duncan E.
Scerif, Gaia
Baker, Kate
author_facet O’Brien, Sinéad
Ng-Cordell, Elise
Astle, Duncan E.
Scerif, Gaia
Baker, Kate
author_sort O’Brien, Sinéad
collection PubMed
description BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s11689-019-9278-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-66834282019-08-09 STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics O’Brien, Sinéad Ng-Cordell, Elise Astle, Duncan E. Scerif, Gaia Baker, Kate J Neurodev Disord Research BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s11689-019-9278-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-06 /pmc/articles/PMC6683428/ /pubmed/31387522 http://dx.doi.org/10.1186/s11689-019-9278-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
O’Brien, Sinéad
Ng-Cordell, Elise
Astle, Duncan E.
Scerif, Gaia
Baker, Kate
STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
title STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
title_full STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
title_fullStr STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
title_full_unstemmed STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
title_short STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
title_sort stxbp1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683428/
https://www.ncbi.nlm.nih.gov/pubmed/31387522
http://dx.doi.org/10.1186/s11689-019-9278-9
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