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It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene\u2013brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering.<\/jats:p>\n               <jats:p>We studied a four-generation family, 16 family members were included in genotyping analysis. T1-weighted and diffusion-weighted MRI scans were conducted on seven family members (six male; aged 9\u201363 years) with two age and sex matched controls without stuttering (n = 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography.<\/jats:p>\n               <jats:p>We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca\u2019s area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold of P &amp;lt; 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (left P = 0.017; right P = 0.037), and a larger right globus pallidus was associated with more severe stuttering (rho = 0.86, P = 0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype.<\/jats:p>\n               <jats:p>Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca\u2019s area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering.<\/jats:p>","DOI":"10.1093\/brain\/awab364","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T19:24:29Z","timestamp":1633461869000},"page":"1177-1188","source":"Crossref","is-referenced-by-count":18,"title":["Atypical development of Broca\u2019s area in a large family with inherited stuttering"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-0910","authenticated-orcid":false,"given":"Daisy G Y","family":"Thompson-Lake","sequence":"first","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Scerri","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville 3052 , Australia"},{"name":"Department of Medical Biology, University of Melbourne , 1G Royal Parade, Parkville 305 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Block","sequence":"additional","affiliation":[{"name":"Discipline of Speech Pathology, School of Allied Health, Human Services & Sport, La Trobe University , Bundoora 3086 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J","family":"Turner","sequence":"additional","affiliation":[{"name":"Speech and Language, Murdoch Children\u2019s Research Institute , Parkville 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheena","family":"Reilly","sequence":"additional","affiliation":[{"name":"Speech and Language, Murdoch Children\u2019s Research Institute , Parkville 3052 , Australia"},{"name":"Menzies Health Institute Queensland, Griffith University , Southport 4215 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaina","family":"Kefalianos","sequence":"additional","affiliation":[{"name":"Speech and Language, Murdoch Children\u2019s Research Institute , Parkville 3052 , Australia"},{"name":"Department of Audiology and Speech Pathology, University of Melbourne , Parkville 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra F","family":"Bonthrone","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Helbig","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 \u00a0 USA"},{"name":"The Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia , Philadelphia, PA 19104 \u00a0 USA"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 \u00a0 USA"},{"name":"Department of Neurology, University of Pennsylvania, Perelman School of Medicine , Philadelphia, PA 19104 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5132-0774","authenticated-orcid":false,"given":"Melanie","family":"Bahlo","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville 3052 , Australia"},{"name":"Department of Medical Biology, University of Melbourne , 1G Royal Parade, Parkville 305 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid E","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Melbourne, Austin Hospital , Heidelberg 3084 , Australia"},{"name":"Department of Paediatrics, University of Melbourne, Royal Children's Hospital , Parkville 3052 , Australia"},{"name":"Murdoch Children\u2019s Research Institute , Parkville 3052 , Australia"},{"name":"Florey Institute of Neuroscience and Mental Health , Parkville 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Melbourne, Austin Hospital , Heidelberg 3084 , Australia"},{"name":"Murdoch Children\u2019s Research Institute , Parkville 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique J","family":"Li\u00e9geois","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7405","authenticated-orcid":false,"given":"Angela T","family":"Morgan","sequence":"additional","affiliation":[{"name":"Speech and Language, Murdoch Children\u2019s Research Institute , Parkville 3052 , Australia"},{"name":"Department of Audiology and Speech Pathology, University of Melbourne , Parkville 3052 , Australia"},{"name":"Department of Paediatrics, University of Melbourne, Royal Children's Hospital , Parkville 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"issue":"2","key":"2023020110260392800_awab364-B1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jfludis.2012.11.002","article-title":"Epidemiology of stuttering: 21st century advances","volume":"38","author":"Yairi","year":"2013","journal-title":"J Fluency Disord."},{"issue":"10","key":"2023020110260392800_awab364-B2","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1044\/2017_JSLHR-S-16-0205","article-title":"The history of stuttering by 7 years of age: Follow-up of a prospective community cohort","volume":"60","author":"Kefalianos","year":"2017","journal-title":"J Speech Lang Hear Res."},{"issue":"6","key":"2023020110260392800_awab364-B3","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1044\/1092-4388(2002\/088)","article-title":"Epidemiology of stuttering in the community across the entire life span","volume":"45","author":"Craig","year":"2002","journal-title":"J Speech Lang Hear Res."},{"issue":"1","key":"2023020110260392800_awab364-B4","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1038\/s41598-017-04357-6","article-title":"Hemodynamics of speech production: An fNIRS investigation of children who stutter","volume":"7","author":"Walsh","year":"2017","journal-title":"Sci Rep."},{"issue":"7","key":"2023020110260392800_awab364-B5","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1044\/2018_JSLHR-S-17-0353","article-title":"Stuttering and labor market outcomes in the United 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