title: GRIN2A: an aptly named gene for speech dysfunction.
abstract: OBJECTIVE
  To delineate the specific speech deficits in individuals with epilepsy-aphasia syndromes associated with mutations in the glutamate receptor subunit gene GRIN2A.
  
  
  METHODS
  We analyzed the speech phenotype associated with GRIN2A mutations in 11 individuals, aged 16 to 64 years, from 3 families. Standardized clinical speech assessments and perceptual analyses of conversational samples were conducted.
  
  
  RESULTS
  Individuals showed a characteristic phenotype of dysarthria and dyspraxia with lifelong impact on speech intelligibility in some. Speech was typified by imprecise articulation (11/11, 100%), impaired pitch (monopitch 10/11, 91%) and prosody (stress errors 7/11, 64%), and hypernasality (7/11, 64%). Oral motor impairments and poor performance on maximum vowel duration (8/11, 73%) and repetition of monosyllables (10/11, 91%) and trisyllables (7/11, 64%) supported conversational speech findings. The speech phenotype was present in one individual who did not have seizures.
  
  
  CONCLUSIONS
  Distinctive features of dysarthria and dyspraxia are found in individuals with GRIN2A mutations, often in the setting of epilepsy-aphasia syndromes; dysarthria has not been previously recognized in these disorders. Of note, the speech phenotype may occur in the absence of a seizure disorder, reinforcing an important role for GRIN2A in motor speech function. Our findings highlight the need for precise clinical speech assessment and intervention in this group. By understanding the mechanisms involved in GRIN2A disorders, targeted therapy may be designed to improve chronic lifelong deficits in intelligibility.
authors.affiliation: From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Turner
authors.affiliation: From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia.
authors.forename: Angela K
authors.initials: AK
authors.lastname: Mayes
authors.affiliation: From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Verhoeven
authors.affiliation: From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Mandelstam
authors.affiliation: From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia.
authors.forename: Angela T
authors.initials: AT
authors.lastname: Morgan
authors.affiliation: From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia. scheffer@unimelb.edu.au.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D001039:Aphasia, Broca / Q000235:genetics; D001072:Apraxias / Q000235:genetics*; D004401:Dysarthria / Q000235:genetics*; D004827:Epilepsy / Q000150:complications; D005260:Female; D006801:Humans; D007806:Language Disorders / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011597:Psychomotor Performance; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D013064:Speech Disorders / Q000235:genetics*; D013065:Speech Intelligibility; D055815:Young Adult
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate