title: The clinical syndrome of dystonia with anarthria/aphonia.
abstract: OBJECTIVE
  In dystonia the formulation of a clinical syndrome is paramount to refine the list of etiologies. We here describe the rare association of dystonia with anarthria/aphonia, by examining a large cohort of patients, to provide a narrow field of underlying conditions and a practical algorithmic approach to reach diagnosis.
  
  
  METHODS
  We retrospectively reviewed cases, which were evaluated between 2005 and 2014, to identify those with dystonia combined with marked anarthria and/or aphonia. We reviewed demographic information, clinical characteristics, as well as clinico-genetic investigations. We evaluated video material where available.
  
  
  RESULTS
  From 860 cases with dystonia as the predominant motor feature, we identified 32 cases (3.7%) with anarthria/aphonia. Age at neurological symptom onset was variable, but the majority of cases (n = 20) developed symptoms within their first eight years of life. A conclusive diagnosis was reached in 27 cases. Monoamine neurotransmitter disorders, neurodegeneration with brain iron accumulation syndromes, hypomyelination with atrophy of the basal ganglia and cerebellum, and syndromes with inborn errors of metabolism were the most common diagnoses. Brain MRI was crucial for reaching a diagnosis by examining the structural integrity of the basal ganglia, the cerebral cortex, brain myelination and whether there was abnormal metal deposition. Pathophysiological mechanisms underlying anarthria/aphonia included dystonia, corticobulbar involvement, apraxia and abnormalities of brain development.
  
  
  CONCLUSIONS
  The spectrum of conditions that may present with the syndrome of dystonia with anarthria/aphonia is broad. Various causes may account for the profound speech disturbance. A practical brain MRI-based algorithm is provided to aid the diagnostic procedure.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK; Department of Neurology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Ganos
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK.
authors.forename: Belinda
authors.initials: B
authors.lastname: Crowe
authors.affiliation: Second Department of Neurology, University of Athens, Athens, Greece; Neurology Clinic, Philipps University, Marburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.affiliation: Institute of Neurology, CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kresojević
authors.affiliation: Institute of Neurology, CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Milica Ječmenica
authors.initials: MJ
authors.lastname: Lukić
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Funmilola
authors.initials: F
authors.lastname: Taiwo
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Bettina
authors.initials: B
authors.lastname: Balint
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Amit
authors.initials: A
authors.lastname: Batla
authors.affiliation: Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Roberto
authors.initials: R
authors.lastname: Erro
authors.affiliation: Institute of Neurology, CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.affiliation: Institute of Neurology, CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kostić
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK; Molecular Neurosciences, Developmental Neurosciences, UCL-Institute of Child Health, London, UK.
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK. Electronic address: K.bhatia@ucl.ac.uk.
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001044:Aphonia / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004421:Dystonia / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D002265:Carboxylic Ester Hydrolases; C576043:SERAC1 protein, human
keywords: Anarthria; Aphonia; Dystonia; Speech disorder