Childhood-onset progressive dystonia associated with pathogenic truncating variants in CHD8.

ABSTRACT: 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

SUBMITTER: Doummar D 

PROVIDER: S-EPMC8528468 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature