Genetic Etiologies of Dystonia with Anarthria/Aphonia
Anika Ménétrey, Eriberto Rayco, Maziar Emamikhah Abarghouei, Susan H. Fox, Anthony E. Lang, George M. Ibrahim, Carolina Gorodetsky, Christos GanosAbstract
Background
Dystonia with anarthria and/or aphonia (DAnAp) represents a distinctive phenotype manifesting across lifespan. Frequently associated with genetic disorders, early recognition is critical for diagnosis and management.
Objectives
To provide practical recommendations for the clinical evaluation of patients with DAnAp, enhancing recognition and facilitating targeted diagnostic workup.
Methods
We retrospectively reviewed patients with dystonia and anarthria/aphonia due to established genetic causes across the lifespan at The Hospital for Sick Children and Toronto Western Hospital. Demographic, clinical, genetic, and neuroradiological data were reviewed. Cases were categorized based on the age of onset of neurological symptoms: neonatal (0–4 weeks), infantile (4 weeks – 1 year), early childhood (1–8 years), late childhood/adolescence (8–18 years) and adulthood (>18 years).
Results
Fifty‐four patients were included, with a mean age of 15.8 years at last assessment (range: 17 months–53 years). We identified 39 distinct genetic etiologies including channelopathies, G‐protein‐related disorders, developmental and epileptic encephalopathies and metabolic disorders. Most (92%) presented before the age of 8 years, with symptom onset in infancy (37%), early childhood (32%) and neonatal period (24%); only four presented later. Early‐onset cases demonstrated more severe phenotypes, including global developmental delay (100% of neonatal cases), seizures (54% of neonatal cases) and absent speech acquisition. Therapeutic interventions included deep brain stimulation in 12 patients, targeted gene or disease‐specific therapies were available for three patients in our cohort.
Conclusion
Dystonia with anarthria/aphonia is genetically heterogeneous and predominantly early‐onset, with severe neurodevelopmental impairment. Early genetic diagnosis is essential to guide management as targeted therapies emerge.