Ruth O Braden1,2, David J Amor1,2,3,4, Simon E Fisher5,6, Cristina Mei1,7, Candace T Myers8, Heather Mefford8, Deepak Gill9, Siddharth Srivastava10, Lindsay C Swanson10, Himanshu Goel11, Ingrid E Scheffer1,2,3,12,13, Angela T Morgan1,2,3,4. 1. Murdoch Children's Research Institute, Parkville, VIC, Australia. 2. Department of Audiology and Speech Pathology and Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia. 3. The Royal Children's Hospital, Parkville, VIC, Australia. 4. Victorian Clinical Genetics Service, Parkville, VIC, Australia. 5. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands. 6. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. 7. Orygen and Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia. 8. Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA. 9. TY Nelson Department of Neurology, The Children's Hospital at Westmead, Sydney, NSW, Australia. 10. Department of Neurology, Boston Children's Hospital, Boston, MA, USA. 11. Hunter Genetics, John Hunter Hospital, New Lambton Heights, NSW, Australia. 12. Austin Health, Heidelberg, Melbourne, VIC, Australia. 13. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
Abstract
AIM: To delineate the speech and language phenotype of a cohort of individuals with FOXP1-related disorder. METHOD: We administered a standardized test battery to examine speech and oral motor function, receptive and expressive language, non-verbal cognition, and adaptive behaviour. Clinical history and cognitive assessments were analysed together with speech and language findings. RESULTS: Twenty-nine patients (17 females, 12 males; mean age 9y 6mo; median age 8y [range 2y 7mo-33y]; SD 6y 5mo) with pathogenic FOXP1 variants (14 truncating, three missense, three splice site, one in-frame deletion, eight cytogenic deletions; 28 out of 29 were de novo variants) were studied. All had atypical speech, with 21 being verbal and eight minimally verbal. All verbal patients had dysarthric and apraxic features, with phonological deficits in most (14 out of 16). Language scores were low overall. In the 21 individuals who carried truncating or splice site variants and small deletions, expressive abilities were relatively preserved compared with comprehension. INTERPRETATION: FOXP1-related disorder is characterized by a complex speech and language phenotype with prominent dysarthria, broader motor planning and programming deficits, and linguistic-based phonological errors. Diagnosis of the speech phenotype associated with FOXP1-related dysfunction will inform early targeted therapy. What this paper adds Individuals with FOXP1-related disorder have a complex speech and language phenotype. Dysarthria, which impairs intelligibility, is the dominant feature of the speech profile. No participants were receiving speech therapy for dysarthria, but were good candidates for therapy Features of speech apraxia occur alongside persistent phonological errors. Language abilities are low overall; however, expressive language is a relative strength.
AIM: To delineate the speech and language phenotype of a cohort of individuals with FOXP1-related disorder. METHOD: We administered a standardized test battery to examine speech and oral motor function, receptive and expressive language, non-verbal cognition, and adaptive behaviour. Clinical history and cognitive assessments were analysed together with speech and language findings. RESULTS: Twenty-nine patients (17 females, 12 males; mean age 9y 6mo; median age 8y [range 2y 7mo-33y]; SD 6y 5mo) with pathogenic FOXP1 variants (14 truncating, three missense, three splice site, one in-frame deletion, eight cytogenic deletions; 28 out of 29 were de novo variants) were studied. All had atypical speech, with 21 being verbal and eight minimally verbal. All verbal patients had dysarthric and apraxic features, with phonological deficits in most (14 out of 16). Language scores were low overall. In the 21 individuals who carried truncating or splice site variants and small deletions, expressive abilities were relatively preserved compared with comprehension. INTERPRETATION: FOXP1-related disorder is characterized by a complex speech and language phenotype with prominent dysarthria, broader motor planning and programming deficits, and linguistic-based phonological errors. Diagnosis of the speech phenotype associated with FOXP1-related dysfunction will inform early targeted therapy. What this paper adds Individuals with FOXP1-related disorder have a complex speech and language phenotype. Dysarthria, which impairs intelligibility, is the dominant feature of the speech profile. No participants were receiving speech therapy for dysarthria, but were good candidates for therapy Features of speech apraxia occur alongside persistent phonological errors. Language abilities are low overall; however, expressive language is a relative strength.
Authors: Antony Kaspi; Angela T Morgan; Michael S Hildebrand; Victoria E Jackson; Ruth Braden; Olivia van Reyk; Tegan Howell; Simone Debono; Mariana Lauretta; Lottie Morison; Matthew J Coleman; Richard Webster; David Coman; Himanshu Goel; Mathew Wallis; Gabriel Dabscheck; Lilian Downie; Emma K Baker; Bronwyn Parry-Fielder; Kirrie Ballard; Eva Harrold; Shaun Ziegenfusz; Mark F Bennett; Erandee Robertson; Longfei Wang; Amber Boys; Simon E Fisher; David J Amor; Ingrid E Scheffer; Melanie Bahlo Journal: Mol Psychiatry Date: 2022-09-18 Impact factor: 13.437
Authors: Lottie D Morison; Ruth O Braden; David J Amor; Amanda Brignell; Bregje W M van Bon; Angela T Morgan Journal: Eur J Hum Genet Date: 2022-04-18 Impact factor: 5.351