Open AccessChildhood‐onset progressive dystonia associated with pathogenic truncating variants in CHD8
Author(s) -
Doummar Diane,
Treven Marco,
Qebibo Leila,
Devos David,
Ghoumid Jamal,
Ravelli Claudia,
Kranz Gottfried,
Krenn Martin,
Demailly Diane,
Cif Laura,
Davion JeanBaptiste,
Zimprich Fritz,
Burglen Lydie,
Zech Michael
Publication year - 2021
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51444
Subject(s) - dystonia , medicine , exome sequencing , frameshift mutation , autism spectrum disorder , nonsense , phenotype , deep brain stimulation , neurodevelopmental disorder , intellectual disability , autism , pediatrics , bioinformatics , genetics , gene , psychiatry , disease , biology , parkinson's disease
Originally described as a risk factor for autism, CHD8 loss‐of‐function variants have recently been associated with a wider spectrum of neurodevelopmental abnormalities. We further expand the CHD8 ‐related phenotype with the description of two unrelated patients who presented with childhood‐onset progressive dystonia. Whole‐exome sequencing conducted in two independent laboratories revealed a CHD8 nonsense variant in one patient and a frameshift variant in the second. The patients had strongly overlapping phenotypes characterized by generalized dystonia with mild‐to‐moderate neurodevelopmental comorbidity. Deep brain stimulation led to clinical improvement in both cases. We suggest that CHD8 should be added to the growing list of neurodevelopmental disorder‐associated genes whose mutations can also result in dystonia‐dominant phenotypes.