Objective: This study provides a comprehensive list of genetic causes in a large cohort of 53 pediatric and adult patients with dystonia and anarthria or aphonia.

Background: Dystonia is a movement disorder with various etiologies, many of which are genetic. Specific syndromic associations, like the co-occurrence of prominent dystonia with anarthria/aphonia may often guide diagnostic considerations. This study presents the largest cohort of genetically diagnosed pediatric and adult patients with dystonia and anarthria/aphonia.

Method: Data from Toronto Western Hospital and The Hospital for Sick Children, were analyzed. Fifty-three patients with dystonia with anarthria/aphonia and an established genetic diagnosis were included. 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 – 1year), early childhood (1 – 8 years), late childhood/adolescence (8 – 18 years) and adulthood (>18 years).

Results: The cohort of 53 patients had a mean age of 15.3 years (range: 17 months–53 years). Twenty-five patients were female, and 28 males; 13.2% (n = 7) had died prior to data collection. The largest group of patients (37.7%) had infantile onset, followed by early childhood (34%) and neonatal onset (24.5%). Only two cases had onset either in late childhood/adolescence (n=1) or adulthood (n=1). Genetic causes of dystonia with anarthria/aphonia according to symptom onset included: neonatal onset: KCNQ2, GNAO1, and sodium channel disorders; infantile onset: Lesch-Nyhan, BCAP31, Pantothenate kinase-associated neurodegeneration; onset in early childhood:

Beta-propeller protein-associated neurodegeneration, MECP2, UBE3A; later onset: X-linked adrenoleukodystrophy and neuronal ceroid lipofuscinosis. Global developmental delay, seizures as well as the complete absence of speech acquisition were most prominent in the neonatal and infantile-onset groups, correlating with the severity of the underlying genetic conditions.

Conclusion: This cohort provides a comprehensive understanding of the genetic causes of dystonia with anarthria/aphonia across various age groups. By analyzing 53 genetically confirmed cases, we identified several genetic and metabolic disorders, highlighting some of the complex genetic architecture underlying this clinical syndrome.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/from-syndrome-to-genetics-genetic-etiologies-of-dystonia-with-anarthria-aphonia/