Childhood‐onset progressive dystonia associated with pathogenic truncating variants in CHD8

Diane Doummar (1) , Marco Treven (2) , Leila Qebibo (1) , David Devos (3) , Jamal Ghoumid (4) , Claudia Ravelli (1) , Gottfried Kranz , Martin Krenn (2, 5) , Diane Demailly (6) , Laura Cif (6) , Jean‐baptiste Davion (7) , Fritz Zimprich (2) , Lydie Burglen (1, 8) , Michael Zech (5)

1 CHU Trousseau [APHP]
2 Medizinische Universität Wien = Medical University of Vienna
3 LilNCog - Lille Neurosciences & Cognition - U 1172
4 RADEME - Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364
5 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
6 Service de Neurochirurgie [CHRU Montpellier]
7 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
8 BBF - Biodiversité et Biotechnologie Fongiques

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 dystoniadominant phenotypes.

Domaines: Neurosciences [q-bio.NC]; Pédiatrie; Génétique humaine

Diane Doummar, Marco Treven, Leila Qebibo, David Devos, Jamal Ghoumid, et al.. Childhood‐onset progressive dystonia associated with pathogenic truncating variants in CHD8. Annals of Clinical and Translational Neurology, In press, ⟨10.1002/acn3.51444⟩. ⟨hal-03348952⟩