title: A highly penetrant form of childhood apraxia of speech due to deletion of 16p11.2.
abstract: Individuals with heterozygous 16p11.2 deletions reportedly suffer from a variety of difficulties with speech and language. Indeed, recent copy-number variant screens of children with childhood apraxia of speech (CAS), a specific and rare motor speech disorder, have identified three unrelated individuals with 16p11.2 deletions. However, the nature and prevalence of speech and language disorders in general, and CAS in particular, is unknown for individuals with 16p11.2 deletions. Here we took a genotype-first approach, conducting detailed and systematic characterization of speech abilities in a group of 11 unrelated children ascertained on the basis of 16p11.2 deletions. To obtain the most precise and replicable phenotyping, we included tasks that are highly diagnostic for CAS, and we tested children under the age of 18 years, an age group where CAS has been best characterized. Two individuals were largely nonverbal, preventing detailed speech analysis, whereas the remaining nine met the standard accepted diagnostic criteria for CAS. These results link 16p11.2 deletions to a highly penetrant form of CAS. Our findings underline the need for further precise characterization of speech and language profiles in larger groups of affected individuals, which will also enhance our understanding of how genetic pathways contribute to human communication disorders.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Evelina
authors.initials: E
authors.lastname: Fedorenko
authors.affiliation: Language and Literacy Group, Murdoch Childrens Research Institute, Melbourne, VIC, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Morgan
authors.affiliation: Language and Literacy Group, Murdoch Childrens Research Institute, Melbourne, VIC, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murray
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Cardinaux
authors.affiliation: Language and Literacy Group, Murdoch Childrens Research Institute, Melbourne, VIC, Australia.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mei
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Tager-Flusberg
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.|McGovern Institute for Brain Research, Cambridge, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kanwisher
mesh_terms: D000293:Adolescent; D001072:Apraxias / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D017384:Sequence Deletion / Q000235:genetics*; D013064:Speech Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology