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CHD8-related disorders redefined: an expanding spectrum of dystonic phenotypes

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Titel: CHD8-related disorders redefined: an expanding spectrum of dystonic phenotypes
Autoren: Ugo Sorrentino, Sylvia Boesch, Diane Doummar, Claudia Ravelli, Tereza Serranova, Elisabetta Indelicato, Juliane Winkelmann, Lydie Burglen, Robert Jech, Michael Zech
Quelle: J Neurol
Journal of Neurology
Verlagsinformationen: Springer Science and Business Media LLC, 2024.
Publikationsjahr: 2024
Schlagwörter: Adult, 0301 basic medicine, 0303 health sciences, Adolescent, ddc, 3. Good health, Short Commentary, Movement disorders, Dystonia, Exome sequencing, Autism, DNA-Binding Proteins, Young Adult, 03 medical and health sciences, Phenotype, Neurodevelopmental Disorders, Dystonic Disorders, Child, Preschool, Humans, Female, Child, Frameshift Mutation, Dystonia/genetics [MeSH], Dystonia/diagnosis [MeSH], Transcription Factors/genetics [MeSH], Frameshift Mutation [MeSH], Neurodevelopmental Disorders/diagnosis [MeSH], DNA-Binding Proteins/genetics [MeSH], Neurodevelopmental Disorders/genetics [MeSH], Dystonia/etiology [MeSH], Dystonic Disorders/complications [MeSH], Phenotype [MeSH], Dystonic Disorders/diagnosis [MeSH], Child [MeSH], Adolescent [MeSH], Female [MeSH], Adult [MeSH], Humans [MeSH], Dystonic Disorders/physiopathology [MeSH], Dystonic Disorders/genetics [MeSH], Young Adult [MeSH], Dystonia/physiopathology [MeSH], Child, Preschool [MeSH], Transcription Factors
Beschreibung: Background Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems. However, the complete phenotypic spectrum of CHD8-related disorders is still undefined. In 2021, our group described two singular female patients with CHD8-related neurodevelopmental disorder and striking dystonic manifestations, prompting the suggestion that dystonia should be considered a possible component of this condition. Case series presentation We describe three additional unrelated female individuals, each carrying a different CHD8 frameshift variant and whose clinical presentations were primarily characterized by young-onset dystonia. Their dystonic manifestations were remarkably heterogeneous and ranged from focal, exercise-dependent, apparently isolated forms to generalized permanent phenotypes accompanied by spasticity and tremor. Neurocognitive impairment and autistic behaviors, typical of CHD8-related disorders, were virtually absent or at the mild end of the spectrum. Conclusions This work validates our previous observation that dystonia is part of the phenotypic spectrum of CHD8-related neurodevelopmental disorders with potential female preponderance, raising new challenges and opportunities in the diagnosis and management of this condition. It also highlights the importance of in-depth neurologic phenotyping of patients carrying variants associated with neurodevelopmental disorders, as the connection between neurodevelopmental and movement disorders is proving closer than previously appreciated.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1432-1459
0340-5354
DOI: 10.1007/s00415-024-12271-x
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/38441608
https://repository.publisso.de/resource/frl:6509772
https://epub.ub.uni-muenchen.de/117648/
https://mediatum.ub.tum.de/1770808
Rights: CC BY
Dokumentencode: edsair.doi.dedup.....7a2e3550b01f47f083338f401ac5f5da
Datenbank: OpenAIRE
Beschreibung
Abstract:Background Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems. However, the complete phenotypic spectrum of CHD8-related disorders is still undefined. In 2021, our group described two singular female patients with CHD8-related neurodevelopmental disorder and striking dystonic manifestations, prompting the suggestion that dystonia should be considered a possible component of this condition. Case series presentation We describe three additional unrelated female individuals, each carrying a different CHD8 frameshift variant and whose clinical presentations were primarily characterized by young-onset dystonia. Their dystonic manifestations were remarkably heterogeneous and ranged from focal, exercise-dependent, apparently isolated forms to generalized permanent phenotypes accompanied by spasticity and tremor. Neurocognitive impairment and autistic behaviors, typical of CHD8-related disorders, were virtually absent or at the mild end of the spectrum. Conclusions This work validates our previous observation that dystonia is part of the phenotypic spectrum of CHD8-related neurodevelopmental disorders with potential female preponderance, raising new challenges and opportunities in the diagnosis and management of this condition. It also highlights the importance of in-depth neurologic phenotyping of patients carrying variants associated with neurodevelopmental disorders, as the connection between neurodevelopmental and movement disorders is proving closer than previously appreciated.
ISSN:14321459
03405354
DOI:10.1007/s00415-024-12271-x