Genetic Etiologies of Dystonia with Anarthria/Aphonia.
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.
To provide practical recommendations for the clinical evaluation of patients with DAnAp, enhancing recognition and facilitating targeted diagnostic workup.
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).
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.
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.
To provide practical recommendations for the clinical evaluation of patients with DAnAp, enhancing recognition and facilitating targeted diagnostic workup.
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).
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.
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.
Authors
Ménétrey Ménétrey, Rayco Rayco, Abarghouei Abarghouei, Fox Fox, Lang Lang, Ibrahim Ibrahim, Gorodetsky Gorodetsky, Ganos Ganos
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