Adult Phenotype of CHD2-Associated Disorders

Background and Objectives Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of...

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Autores: Rong, Marlene, Ali, Quratulain Zulfiqar, Aledo-Serrano, Angel, Bayat, Allan, Devinsky, Orrin, Qaiser, Farah, Chandran, Ilakkiah, Ali, Anum, Fasano, Alfonso, Bassett, Anne S., Andrade, Danielle M.
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/7629
Acceso en línea:https://hdl.handle.net/10641/7629
Access Level:acceso abierto
Palabra clave:Clinical Neurology
Genetics(clinical)
Journal Article
Yes
yes
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spelling Adult Phenotype of CHD2-Associated DisordersRong, MarleneAli, Quratulain ZulfiqarAledo-Serrano, AngelBayat, AllanDevinsky, OrrinQaiser, FarahChandran, IlakkiahAli, AnumFasano, AlfonsoBassett, Anne S.Andrade, Danielle M.Clinical NeurologyGenetics(clinical)Journal ArticleYesyesBackground and Objectives Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants. Methods Patients 18 years or older with likely pathogenic or pathogenic (LP/P) CHD2 variants were included. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder, and adaptive behavioral skills of patients. Results In this prospective study, 14 unrelated adult patients (age range: 18–45 years, median: 21 years) with LP/P CHD2 variants were described. Eleven novel variants were identified. No genotype-phenotype correlations were identified. 79% of adults still have ongoing seizures. Photosensitivity was present in 64% of adult patients. Autism spectrum disorder was diagnosed in 71% of patients. Only 29% were able to read and understand material at a sixth-grade level or higher. Behavioral issues were reported in 100% of adult patients, and 71% had internalizing features, such as anxiety. Self-injurious behaviors were present in 50%. Only 43% could ambulate independently. Additional characteristics included reflux (36%), constipation (71%), and abnormal pain responsiveness (43%). 1 patient presented with nonepileptic breath-holding spells leading to cyanosis. No patient could perform all basic activities of daily living independently, all the time. Higher seizure severity was associated with worse nonseizure outcomes (p = 0.04). Discussion Most adults with CHD2 continue to have seizures, and seizure severity is associated with worse comorbidities such as maladaptive behaviors, gait, gastrointestinal, sleep, and abnormal pain responsiveness. Longevity has not been systematically studied in this group of patients. Here we describe a group of adult patients (up to 45 years of age) and the natural history of this condition. These data may provide prognostic insights for families of pediatric patients and help identify key points to be addressed in future precision trials for patients with CHD2 variants.Facultad de Ciencias Experimentales20242024-11-2520242024-11-25journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/7629reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/76292026-06-11T12:44:57Z
dc.title.none.fl_str_mv Adult Phenotype of CHD2-Associated Disorders
title Adult Phenotype of CHD2-Associated Disorders
spellingShingle Adult Phenotype of CHD2-Associated Disorders
Rong, Marlene
Clinical Neurology
Genetics(clinical)
Journal Article
Yes
yes
title_short Adult Phenotype of CHD2-Associated Disorders
title_full Adult Phenotype of CHD2-Associated Disorders
title_fullStr Adult Phenotype of CHD2-Associated Disorders
title_full_unstemmed Adult Phenotype of CHD2-Associated Disorders
title_sort Adult Phenotype of CHD2-Associated Disorders
dc.creator.none.fl_str_mv Rong, Marlene
Ali, Quratulain Zulfiqar
Aledo-Serrano, Angel
Bayat, Allan
Devinsky, Orrin
Qaiser, Farah
Chandran, Ilakkiah
Ali, Anum
Fasano, Alfonso
Bassett, Anne S.
Andrade, Danielle M.
author Rong, Marlene
author_facet Rong, Marlene
Ali, Quratulain Zulfiqar
Aledo-Serrano, Angel
Bayat, Allan
Devinsky, Orrin
Qaiser, Farah
Chandran, Ilakkiah
Ali, Anum
Fasano, Alfonso
Bassett, Anne S.
Andrade, Danielle M.
author_role author
author2 Ali, Quratulain Zulfiqar
Aledo-Serrano, Angel
Bayat, Allan
Devinsky, Orrin
Qaiser, Farah
Chandran, Ilakkiah
Ali, Anum
Fasano, Alfonso
Bassett, Anne S.
Andrade, Danielle M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias Experimentales
dc.subject.none.fl_str_mv Clinical Neurology
Genetics(clinical)
Journal Article
Yes
yes
topic Clinical Neurology
Genetics(clinical)
Journal Article
Yes
yes
description Background and Objectives Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants. Methods Patients 18 years or older with likely pathogenic or pathogenic (LP/P) CHD2 variants were included. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder, and adaptive behavioral skills of patients. Results In this prospective study, 14 unrelated adult patients (age range: 18–45 years, median: 21 years) with LP/P CHD2 variants were described. Eleven novel variants were identified. No genotype-phenotype correlations were identified. 79% of adults still have ongoing seizures. Photosensitivity was present in 64% of adult patients. Autism spectrum disorder was diagnosed in 71% of patients. Only 29% were able to read and understand material at a sixth-grade level or higher. Behavioral issues were reported in 100% of adult patients, and 71% had internalizing features, such as anxiety. Self-injurious behaviors were present in 50%. Only 43% could ambulate independently. Additional characteristics included reflux (36%), constipation (71%), and abnormal pain responsiveness (43%). 1 patient presented with nonepileptic breath-holding spells leading to cyanosis. No patient could perform all basic activities of daily living independently, all the time. Higher seizure severity was associated with worse nonseizure outcomes (p = 0.04). Discussion Most adults with CHD2 continue to have seizures, and seizure severity is associated with worse comorbidities such as maladaptive behaviors, gait, gastrointestinal, sleep, and abnormal pain responsiveness. Longevity has not been systematically studied in this group of patients. Here we describe a group of adult patients (up to 45 years of age) and the natural history of this condition. These data may provide prognostic insights for families of pediatric patients and help identify key points to be addressed in future precision trials for patients with CHD2 variants.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-11-25
2024
2024-11-25
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/7629
url https://hdl.handle.net/10641/7629
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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