biostudies-literatureUnknown8(10)Doummar DOriginally 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.Annals of clinical and translational neurology1986-1990https://www.ebi.ac.uk/biostudies/studies/S-EPMC8528468biostudies-literatureChildhood-onset progressive dystonia associated with pathogenic truncating variants in CHD8.PMC8528468Burglen LDoummar DDevos DGhoumid JKranz GZech MCif LZimprich FQebibo LDavion JBRavelli CTreven MKrenn MDemailly DfalseChildhood-onset progressive dystonia associated with pathogenic truncating variants in CHD8.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.2021-01-01T00:00:00Z2021 Oct2024-11-15T15:42:24.422Z2024-11-15T15:42:24.422ZS-EPMC85284683441511710.1002/acn3.51444