Deep phenotyping of speech and language skills in individuals with 16p11.2 deletion
Open accessAbstract
Recurrent deletions of a ~600-kb region of 16p11.2 have been associated with a highly penetrant form of childhood apraxia of speech (CAS). Yet prior findings have been based on a small, potentially biased sample using retrospectively collected data. We examine the prevalence of CAS in a larger cohort of individuals with 16p11.2 deletion using a prospectively designed assessment battery. The broader speech and language phenotype associated with carrying this deletion was also examined. 55 participants with 16p11.2 deletion (47 children, 8 adults) underwent deep phenotyping to test for the presence of CAS and other speech and language diagnoses. Standardized tests of oral motor functioning, speech production, language, and non-verbal IQ were conducted. The majority of children (77%) and half of adults (50%) met criteria for CAS. Other speech outcomes were observed including articulation or phonological errors (i.e., phonetic and cognitive-linguistic errors, respectively), dysarthria (i.e., neuromuscular speech disorder), minimal verbal output, and even typical speech in some. Receptive and expressive language impairment was present in 73% and 70% of children, respectively. Co-occurring neurodevelopmental conditions (e.g., autism) and non-verbal IQ did not correlate with the presence of CAS. Findings indicate that CAS is highly prevalent in children with 16p11.2 deletion with symptoms persisting into adulthood for many. Yet CAS occurs in the context of a broader speech and language profile and other neurobehavioral deficits. Further research will elucidate specific genetic and neural pathways leading to speech and language deficits in individuals with 16p11.2 deletions, resulting in more targeted speech therapies addressing etiological pathways.
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Cites
Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
Faith, M. S., Carnell, S., & Kral, T. V. E. (2013) · Human Heredity · doi:10.1159/000353879 · Cited by 7,628 · see citing works
Wechsler Abbreviated Scale of Intelligence
Dumont, R., Willis, J. O., Veizel, K., & Zibulsky, J. (2014) · Wiley eBooks · doi:10.1002/9781118660584.ese2519 · Cited by 5,547 · see citing works
Wechsler Abbreviated Scale of Intelligence
Wechsler, D. (1999) · PsycTESTS Dataset · doi:10.1037/t15170-000 · Cited by 4,681 · see citing works
Peabody Picture Vocabulary Test
Campbell, J. M., & Dommestrup, A. K. (2010) · The Corsini Encyclopedia of Psychology · doi:10.1002/9780470479216.corpsy0649 · Cited by 3,787 · see citing works
Structural Variation of Chromosomes in Autism Spectrum Disorder
Marshall, C. R., Noor, A., Vincent, J. B., Lionel, A. C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.009 · Cited by 1,815 · see citing works
Peabody Picture Vocabulary Test
(2007) · Sage eBooks · doi:10.4135/9781412952644.n336 · Cited by 1,756 · see citing works
Kaufman Brief Intelligence Test
(2012) · SpringerReference · doi:10.1007/springerreference_183806 · Cited by 1,089 · see citing works
de López, K. M. J. (2010) · Cited by 877 · see citing works
Goldman‐Fristoe Test of Articulation 2
(2014) · Encyclopedia of Special Education · doi:10.1002/9781118660584.ese1037 · Cited by 846 · see citing works
Review of Goldman-Fristoe Test of Articulation.
Sherman, D. (1970) · Professional Psychology · doi:10.1037/h0020663 · Cited by 793 · see citing works
A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Girirajan, S., Rosenfeld, J. A., Cooper, G. M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S. E., Baker, C., et al. (2010) · Nature Genetics · doi:10.1038/ng.534 · Cited by 667 · see citing works
Frenchay Dysarthria Assessment
Enderby, P. (1980) · International Journal of Language & Communication Disorders · doi:10.3109/13682828009112541 · Cited by 601 · see citing works
Shriberg, L. D., & Kwiatkowski, J. (1982) · Journal of Speech and Hearing Disorders · doi:10.1044/jshd.4703.256 · Cited by 599 · see citing works
Wilkinson, G. S., & Robertson, G. J. (2006) · PsycTESTS Dataset · doi:10.1037/t27160-000 · Cited by 585 · see citing works
Shinawi, M., Liu, P., Kang, S.-H. L., Shen, J., Belmont, J. W., Scott, D. A., Probst, F. J., Craigen, W. J., Graham, B. H., Pursley, A., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2009.073015 · Cited by 580 · see citing works
An fMRI investigation of syllable sequence production
Bohland, J. W., & Guenther, F. H. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.04.173 · Cited by 545 · see citing works
Trouton, A., Spinath, F. M., & Plomin, R. (2002) · Twin Research · doi:10.1375/136905202320906255 · Cited by 410 · see citing works
Clinical Assessment of Oropharyngeal Motor Development in Young Children
Robbins, J., & Klee, T. M. (1987) · Journal of Speech and Hearing Disorders · doi:10.1044/jshd.5203.271 · Cited by 364 · see citing works
Diagnostic Evaluation of Articulation and Phonology
Dodd, B. J., Hua, Z., Crosbie, S., Holm, A., & Ozanne, A. (2002) · Cited by 354 · see citing works
Fernandez, B. A., Roberts, W., Chung, B., Weksberg, R., Meyn, S., Szatmari, P., Joseph-George, A. M., MacKay, S., Whitten, K., Noble, B., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2009.069369 · Cited by 335 · see citing works
American Speech-Language-Hearing Association (ASHA)
McNeilly, L. G. (2017) · Springer eBooks · doi:10.1007/978-3-319-56782-2_2148-3 · Cited by 319 · see citing works
School-Age Follow-Up of Children With Childhood Apraxia of Speech
Lewis, B. A., Freebairn, L. A., Hansen, A. J., Iyengar, S. K., & Taylor, H. G. (2004) · Language Speech and Hearing Services in Schools · doi:10.1044/0161-1461(2004/014 · Cited by 302 · see citing works
Bijlsma, E. K., Gijsbers, A. C. J., Schuurs-Hoeijmakers, J. H. M., van Haeringen, A., Fransen van de Putte, D. E., Anderlid, B.-M., Lundin, J., Lapunzina, P., Pérez Jurado, L. A., Delle Chiaie, B., et al. (2009) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2009.03.006 · Cited by 282 · see citing works
Self-citationHanson, E., Bernier, R., Porche, K., Jackson, F. I., Goin-Kochel, R. P., Snyder, L. G., Snow, A. V., Wallace, A. S., Campe, K. L., Zhang, Y., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.04.021 · Cited by 277 · see citing works
Kaufman Brief Intelligence Test
Gray, S. A. O. (2012) · Springer eBooks · doi:10.1007/978-1-4419-1698-3_237 · Cited by 260 · see citing works
Developmental Apraxia of Speech
Shriberg, L. D., Aram, D., & Kwiatkowski, J. (1997) · Journal of Speech Language and Hearing Research · doi:10.1044/jslhr.4002.273 · Cited by 222 · see citing works
Steinman, K. J., Spence, S. J., Ramocki, M. B., Proud, M. B., Kessler, S. K., Marco, E. J., Green Snyder, L., D'Angelo, D., Chen, Q., Chung, W. K., et al. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37820 · Cited by 218 · see citing works
Rosenfeld, J. A., Coppinger, J., Bejjani, B. A., Girirajan, S., Eichler, E. E., Shaffer, L. G., & Ballif, B. C. (2010) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9037-4 · Cited by 207 · see citing works
Differential Diagnosis of Children with Suspected Childhood Apraxia of Speech
Murray, E. L., McCabe, P., Heard, R. C., & Ballard, K. J. (2014) · Journal of Speech Language and Hearing Research · doi:10.1044/2014_jslhr-s-12-0358 · Cited by 195 · see citing works
Comprehensive Test of Phonological Processing–Second Edition
Wagner, R. K., Torgesen, J. K., Rashotte, C. A., et al. (2013) · PsycTESTS Dataset · doi:10.1037/t52630-000 · Cited by 182 · see citing works
Encoding, memory, and transcoding deficits in Childhood Apraxia of Speech
Shriberg, L. D., Lohmeier, H. L., Strand, E. A., & Jakielski, K. J. (2012) · Clinical Linguistics & Phonetics · doi:10.3109/02699206.2012.655841 · Cited by 161 · see citing works
A systematic review of treatment outcomes for children with childhood apraxia of speech.
Murray, E., Mccabe, P., & Ballard, K. (2014) · American Journal of Speech-Language Pathology · doi:10.1044/2014_ajslp-13-0035 · Cited by 112 · see citing works
Holm, A., Farrier, F., & Dodd, B. J. (2008) · International Journal of Language & Communication Disorders · doi:10.1080/13682820701445032 · Cited by 101 · see citing works
Who to Refer for Speech Therapy at 4 Years of Age Versus Who to “Watch and Wait”?
Morgan, A. T., Eecen, K. T., Pezic, A., et al. (2017) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2017.02.059 · Cited by 92 · see citing works
Self-citationFunctional Characterization of the Human Speech Articulation Network
Basilakos, A., Smith, K. G., Fillmore, P., Fridriksson, J., & Fedorenko, E. G. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx100 · Cited by 88 · see citing works
Self-citationThe number of genomic copies at the 16p11.2 locus modulates language, verbal memory, and inhibition
Hippolyte, L., Maillard, A. M., Rodriguez-Herreros, B., Pain, A., Martin-Brevet, S., Ferrari, C., Conus, P., Macé, A., Hadjikhani, N., Metspalu, A., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.021 · Cited by 84 · see citing works
A highly penetrant form of childhood apraxia of speech due to deletion of 16p11.2
Fedorenko, E. G., Morgan, A. T., Murray, E. L., Cardinaux, A. L., Mei, C., Tager-Flusberg, H. B., Fisher, S. E., & Kanwisher, N. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.149 · Cited by 75 · see citing works
Self-citationVerbal Motor Production Assessment for Children
Hayden, D., & Square, P. A. (1999) · PsycTESTS Dataset · doi:10.1037/t15167-000 · Cited by 75 · see citing works
A Review of Standardized Tests of Nonverbal Oral and Speech Motor Performance in Children
McCauley, R. J., & Strand, E. A. (2008) · American Journal of Speech-Language Pathology · doi:10.1044/1058-0360(2008/007 · Cited by 73 · see citing works
Newbury, D. F., Mari, F., Akha, E. S., MacDermot, K. D., Canitano, R., Monaco, A. P., Taylor, J. C., Renieri, A., Fisher, S. E., & Knight, S. J. L. (2012) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.166 · Cited by 70 · see citing works
Self-citationSpeech and Language: Translating the Genome
Deriziotis, P., & Fisher, S. E. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.07.002 · Cited by 62 · see citing works
Self-citationLaffin, J. J. S., Raca, G., Jackson, C. A., Strand, E. A., Jakielski, K. J., & Shriberg, L. D. (2012) · Genetics in Medicine · doi:10.1038/gim.2012.72 · Cited by 59 · see citing works
Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome
Raca, G., Baas, B. S., Kirmani, S., Laffin, J. J. S., Jackson, C. A., Strand, E. A., Jakielski, K. J., & Shriberg, L. D. (2012) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.165 · Cited by 58 · see citing works
Intervention for childhood apraxia of speech
Morgan, A. T., & Vogel, A. P. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006278.pub2 · Cited by 54 · see citing works
Self-citationThe phenotype of Floating–Harbor syndrome in 10 patients
White, S. M., Morgan, A. T., Costa, A. D., et al. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33294 · Cited by 54 · see citing works
Self-citationBrisset, S., Capri, Y., Briand‐Suleau, A., Tosca, L., Gras, D., Fauret‐Amsellem, A., Pineau, D., Saada, J., Ortonne, V., Verloès, A., et al. (2015) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2015.07.001 · Cited by 42 · see citing works
Speech and language in a genotyped cohort of individuals with Kabuki syndrome
Morgan, A. T., Mei, C., Costa, A. D., Fifer, J. M., Lederer, D., Benoît, V., McMillin, M. J., Buckingham, K. J., Bamshad, M. J., Pope, K., et al. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37026 · Cited by 39 · see citing works
Self-citationAbnormal auditory and language pathways in children with 16p11.2 deletion
Berman, J., Chudnovskaya, D., Blaskey, L. G., Kuschner, E. S., Mukherjee, P., Buckner, R., Nagarajan, S. S., Chung, W. K., Spiro, J. E., Sherr, E. H., et al. (2015) · NeuroImage Clinical · doi:10.1016/j.nicl.2015.07.006 · Cited by 23 · see citing works
Requests for clarification and children's speech responses: Changing `pasghetti' to `spaghetti'
Gozzard, H., Baker, E., & McCabe, P. (2008) · Child Language Teaching and Therapy · doi:10.1177/0265659008096292 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 8
- Morgan A, Gunther T. Clinical management of articulation impairment in children. In: Dodd B, Morgan A, (eds). Intervention Case Studies of Child Speech Impairment. London: J&R Press; 2017.
- Dodd B. Clinical management of phonological impairment in children. In: Dodd B, Morgan A, (eds). Intervention Case Studies of Child Speech Impairment. London: J&R Press; 2017.
- Morgan A, Murray E. Clinical management of motor speech disorders. In: Dodd B, Morgan A, (eds). Intervention Case Studies of Child Speech Impairment.. London: J&R Press; 2017.
- Wiig EH, Secord WA, Semel E. Clinical Evaluation of Language Fundamentals Preschool-2: Australian Standardised Edition. Sydney: Harcourt Assessment; 2006.
- Semel E, Wiig EH, Secord WA. Clinical Evaluation of Language Fundamentals-4: Australian Standardised Edition. Sydney: Pear- son; 2006.
- Zimmerman IL, Steiner VG, Pond RE. Preschool Language Scales-5: Australian and New Zealand Language Adapted Edition. Sydney: Pearson; 2011.
- Wiig EH, Semel E, Secord WA. Clinical Evaluation of Language Fundamentals-5. San Antonio: Pearson; 2013.
- Wagner R, Torgesen J, Rashotte C, Pearson NA. Comprehensive Test of Phonological Processing-2. Pro-Ed: Austin; 2013.
Cited by
Sorted by citations
16p11.2 Copy Number Variations and Neurodevelopmental Disorders
Rein, B., & Yan, Z. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.001 · Cited by 160 · see citing works
Agarwalla, S., Arroyo, N. S., Long, N. E., O'Brien, W. T., Abel, T., & Bandyopadhyay, S. (2020) · Genes, Brain and Behavior · doi:10.1111/gbb.12681 · Cited by 26 · see citing works
- Authors
- Mei, C., Fedorenko, E., Amor, D. J., Boys, A., Hoeflin, C., Carew, P., Burgess, T., Fisher, S. E., & Morgan, A. T.
- Affiliations
- Murdoch Children's Research Institute (AU)
- Massachusetts General Hospital (US)
- The University of Melbourne (AU)
- Victorian Clinical Genetics Services (AU)
- Massachusetts Institute of Technology (US)
- Max Planck Institute for Psycholinguistics (NL)
- Corresponding author
- Morgan, Angela T.
- ORCID
- Venue
- European Journal of Human Genetics
- Published
- 2018-02-14
- Volume
- 26
- Issue
- 5
- Pages
- 676-686
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC5945616
- OpenAlex
- W2790446932
- Cited by
- 80
- References
- 49
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 15 · 2023: 12 · 2022: 16 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 5
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Simons Foundation
- Max-Planck-Gesellschaft
- State Government of Victoria
- Simons Center for the Social Brain, Massachusetts Institute of Technology
- Medical Research Council
- National Health and Medical Research Council (1116976, 1105008)
- Topics
- Social Sciences › Psychology › Developmental and Educational Psychology › Language Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- 16p11.2 deletion, childhood apraxia of speech, deep phenotyping, prevalence, dysarthria, phonological errors, articulation errors, non-verbal IQ, autism comorbidity, neurodevelopmental disorders, speech therapy
- MeSH terms
- Adolescent, Adult, Apraxias, Autistic Disorder, Calcium-Binding Proteins, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 16, Female, Humans, Language, Male, Intellectual Disability, Nerve Tissue Proteins, Phenotype, Retrospective Studies, Speech, Speech Disorders, Cohort Studies, Sequence Deletion, T-Box Domain Proteins, Chromosome Disorders
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