Purpose:

Chromosome 16p11.2 deletion syndrome (OMIM #611913) is a rare genetic condition resulting from the partial deletion of approximately 35 genes located at Chromosome 16. Affected people exhibit a variable clinical profile, featuring mild dysmorphisms, motor problems, developmental delay, mild intellectual disability (ID), socialization deficits and/or autism spectrum disorder (ASD) traits, and problems with language. Specifically, a precise characterization of the speech, language, and communication (dis)abilities of people with this condition is still pending.

Method:

We used standardized tests and samples of naturalistic speech to provide a longitudinal profile of the speech, language, and communication problems of a boy with Chromosome 16p11.2 deletion syndrome and without ID or ASD.

Results:

The proband shows impaired expressive abilities as well as problems with receptive language, dysprosody, and ASD-like communication deficits, such as impaired interactive skills, perseverative verbal behavior, overabundance of tangential responses, and lack of metapragmatic awareness and communicative use of gaze, meeting the criteria for social pragmatic communication disorder.

Conclusions:

Our results support the view that language and communication impairment should be regarded as one core symptom of Chromosome 16p11.2 deletion syndrome, even without a diagnosis of ASD or ID. Clinical implications of our results, with a focus on therapeutic interventions for children with 16p11.2 deletion syndrome and no ASD or ID, are also discussed.

Supplemental Material:

https://doi.org/10.23641/asha.21561714

References

  • Adams, C. (2002). Practitioner review: The assessment of language pragmatics.The Journal of Child Psychology and Psychiatry, 43(8), 973–987. https://doi.org/10.1111/1469-7610.00226
  • Adams, R. C., Tapia, C., & Council on children with disabilities. (2013). Early intervention, IDEA Part C services, and the medical home: Collaboration for best practice and best outcomes.Pediatrics, 132(4), e1073–e1088. https://doi.org/10.1542/peds.2013-2305
  • Ahtam, B., Link, N., Hoff, E., Grant, P. E., & Kiho, I. (2019). Altered structural brain connectivity involving the dorsal and ventral language pathways in 16p11.2 deletion syndrome.Brain Imaging and Behavior, 13(2), 430–445. https://doi.org/10.1007/s11682-018-9859-3
  • American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
  • American Speech-Language-Hearing Association. (2007). Childhood apraxia of speech [Technical report]. https://www.asha.org/policy/tr2007-00278/
  • Bachmann-Gagescu, R., Mefford, H. C., Cowan, C., Glew, G. M., Hing, A. V., Wallace, S., Bader, P. I., Hamati, A., Reitnauer, P. J., Smith, R., Stockton, D. W., Muhle, H., Helbig, I., Eichler, E. E., Ballif, B. C., Rosenfeld, J., & Tsuchiya, K. D. (2010). Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity.Genetics in Medicine, 12(10), 641–647. https://doi.org/10.1097/GIM.0b013e3181ef4286
  • Baird, G., Simonoff, E., Pickles, A., Chandler, S., Loucas, T., Meldrum, D., & Charman, T. (2006). Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: The Special Needs and Autism Project (SNAP).The Lancet, 368(9531), 210–215. https://doi.org/10.1016/S0140-6736(06)69041-7
  • Ballif, B. C., Hornor, S. A., Jenkins, E., Madan-Khetarpal, S., Surti, U., Jackson, K. E., Asamoah, A., Brock, P. L., Gowans, G. C., Conway, R. L., Graham, J. M., Jr., Medne, L., Zackai, E. H., Shaikh, T. H., Geoghegan, J., Selzer, R. R., Eis, P. S., Bejjani, B. A., & Shaffer, L. G. (2007). Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2.Nature Genetics, 39(9), 1071–1073. https://doi.org/10.1038/ng2107
  • Barge-Schaapveld, D. Q. C. M., Maas, S. M., Polstra, A., Knegt, L. C., & Hennekam, R. C. M. (2011). The atypical 16p11.2 deletion: A not so atypical microdeletion syndrome?.American Journal of Medical Genetics Part A, 155(5), 1066–1072. https://doi.org/10.1002/ajmg.a.33991
  • Baron-Cohen, S., Leslie, A. M., & Frith, U. (1985). Does the autistic child have a “theory of mind”?.Cognition, 21(1), 37–46. https://doi.org/10.1016/0010-0277(85)90022-8
  • Berman, J. I., Chudnovskaya, D., Blaskey, L., Kuschner, E., Mukherjee, P., Buckner, R., Nagarajan, S., Chung, W. K., Sherr, E. H., & Roberts, T. P. (2016). Relationship between M100 auditory evoked response and auditory radiation microstructure in 16p11.2 deletion and duplication carriers.American Journal of Neuroradiology, 37(6), 1178–1184. https://doi.org/10.3174/ajnr.A4687
  • Berman, J. I., Chudnovskaya, D., Blaskey, L., Kuschner, E., Mukherjee, P., Buckner, R., Nagarajan, S., Chung, W. K., Spiro, J. E., Sherr, E. H., & Roberts, T. P. (2015). Abnormal auditory and language pathways in children with 16p11.2 deletion.NeuroImage: Clinical, 9, 50–57. https://doi.org/10.1016/J.Nicl.2015.07.006
  • Bijlsma, E. K., Gijsbers, A. C., Schuurs-Hoeijmakers, J. H., Van Haeringen, A., Fransen van de Putte, D. E., Anderlid, B. M., Lundin, J., Lapunzina, P., Pérez Jurado, L. A., Delle Chiaie, B., Loeys, B., Menten, B., Oostra, A., Verhelst, H., Amor, D. J., Bruno, D. L., van Essen, A. J., Hordijk, R., & Ruivenkamp, C. A. L. (2009). Extending the phenotype of recurrent rearrangements of 16p11.2: Deletions in mentally retarded patients without autism and in normal individuals.European Journal of Medical Genetics, 52(2–3), 77–87. https://doi.org/10.1016/j.ejmg.2009.03.006
  • Blackmon, K., Thesen, T., Green, S., Ben-Avi, E., Wang, X., Fuchs, B., Kuzniecky, R., & Devinsky, O. (2018). Focal cortical anomalies and language impairment in 16p11.2 deletion and duplication syndrome.Cerebral Cortex, 28(7), 2422–2430. https://doi.org/10.1093/cercor/bhx143
  • Bochukova, E. G., Huang, N., Keogh, J., Henning, E., Purmann, C., Blaszczyk, K., Saeed, S., Hamilton-Shield, J., Clayton-Smith, J., O'Rahilly, S., Hurles, M. E., & Farooqi, I. S. (2010). Large, rare chromosomal deletions associated with severe early-onset obesity.Nature, 463(7281), 666–670. https://doi.org/10.1038/nature08689
  • Brock, J., Jarrold, C., Farran, E. K., Laws, G., & Riby, D. M. (2007). Do children with Williams syndrome really have good vocabulary knowledge? Methods for comparing cognitive and linguistic abilities in developmental disorders.Clinical Linguistics & Phonetics, 21(9), 673–688. https://doi.org/10.1017/CBO9781107415324.004
  • Chandler, S., Charman, T., Baird, G., Simonoff, E., Loucas, T., Meldrum, D., Scott, M., & Pickles, A. (2007). Validation of the social communication questionnaire in a population cohort of children with autism spectrum disorders.Journal of the American Academy of Child & Adolescent Psychiatry, 46(10), 1324–1332. https://doi.org/10.1097/chi.0b013e31812f7d8d
  • Chang, Y. S., Owen, J. P., Pojman, N. J., Thieu, T., Bukshpun, P., Wakahiro, M. L., Marco, E. J., Berman, J. I., Spiro, J. E., Chung, W. K., Buckner, R. L., Roberts, T. P. L., Nagarajan, S. S., Sherr, E. H., & Mukherjee, P. (2016). Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications.Human Brain Mapping, 37(8), 2833–2848. https://doi.org/10.1002/hbm.23211
  • Charlop-Christy, M. H., Carpenter, M., Le, L., LeBlanc, L. A., & Kellet, K. (2002). Using the Picture Exchange Communication System (PECS) with children with autism: Assessment of PECS acquisition, speech, social-communicative behavior, and problem behavior.Journal of Applied Behavior Analysis, 35(3), 213–231. https://doi.org/10.1901/jaba.2002.35-213
  • Charman, T., Baird, G., Simonoff, E., Loucas, T., Chandler, S., Meldrum, D., & Pickles, A. (2007). Efficacy of three screening instruments in the identification of autistic-spectrum disorders.The British Journal of Psychiatry, 191(6), 554–559. https://doi.org/10.1192/bjp.bp.107.040196
  • Chung, W. K., Roberts, T. P., Sherr, E. H., Snyder, L. G., & Spiro, J. E. (2021). 16p11.2 deletion syndrome.Current Opinion in Genetics and Development, 68, 49–56. https://doi.org/10.1016/j.gde.2021.01.011
  • Clahsen, H., & Almazan, M. (1998). Syntax and morphology in Williams syndrome.Cognition, 68(3), 167–198. https://doi.org/10.1016/S0010-0277(98)00049-3
  • Condouris, K., Meyer, E., & Tager-Flusberg, H. (2003). The relationship between standardized measures of language and measures of spontaneous speech in children with autism.American Journal of Speech-Language Pathology, 12(3), 349–358. https://doi.org/10.1044/1058-0360(2003/080)
  • Conti-Ramsden, G. (1996). CLAN (Computerized Language Analysis).Child Language Teaching and Therapy, 12(3), 345–349. https://doi.org/10.1177/026565909601200308
  • Demopoulos, C., Kothare, H., Mizuiri, D., Henderson-Sabes, J., Fregeau, B., Tjernagel, J., Houde, J. F., Sherr, E. H., & Nagarajan, S. S. (2018). Abnormal speech motor control in individuals with 16p11.2 deletions.Scientific Reports, 8(1), 1274. https://doi.org/10.1038/s41598-018-19751-x
  • Diez-Itza, E., Martínez, V., Pérez, V., & Fernández-Urquiza, M. (2018). Explicit oral narrative intervention for students with Williams syndrome.Frontiers in Psychology, 8, 2337. https://doi.org/10.3389/fpsyg.2017.02337
  • Diez-Itza, E., Viejo, A., & Fernández-Urquiza, M. (2022). Pragmatic profiles of adults with fragile X syndrome and Williams syndrome.Brain Sciences, 12(3), 385. https://doi.org/10.3390/brainsci12030385
  • Eaves, L. C., Wingert, H. D., Ho, H. H., & Mickelson, E. C. (2006). Screening for autism spectrum disorders with the social communication questionnaire.Journal of Developmental and Behavioral Pediatrics, 27(Suppl. 2), S95–S103. https://doi.org/10.1097/00004703-200604002-00007
  • Esposito, C. M., Enrico, P., Sciortino, D., Caletti, E., Marchetti, G. B., Cesaretti, C., Oldani, L., Fiorentini, A., & Brambilla, P. (2021). Case report: The association between chromosomal anomalies and Cluster A personality disorders: The case of two siblings with 16p11.2 deletion and a review of the literature.Frontiers in Psychiatry, 12, 689359. https://doi.org/10.3389/fpsyt.2021.689359
  • Fedorenko, E., Morgan, A., Murray, E., Cardinaux, A., Mei, C., Tager-Flusberg, H., Fisher, S. E., & Kanwisher, N. (2016). A highly penetrant form of childhood apraxia of speech due to deletion of 16p11.2.European Journal of Human Genetics, 24(2), 302–306. https://doi.org/10.1038/ejhg.2015.149
  • Feng, J., Chen, S., Wang, Y., Liu, Q., Yang, M., Li, X., Nie, C., Qin, J., Chen, H., Yuan, X., Huang, Y., & Zhang, Q. (2019). Maternal exposure to cadmium impairs cognitive development of male offspring by targeting the Coronin-1a signaling pathway.Chemosphere, 225, 765–774. https://doi.org/10.1016/j.chemosphere.2019.03.094
  • Fernandez, B. A., Roberts, W., Chung, B., Weksberg, R., Meyn, S., Szatmari, P., Joseph-George, A. M., MacKay, S., Whitten, K., Noble, B., Vardy, C., Crosbie, V., Luscombe, S., Tucker, E., Turner, L., Marshall, C. R., & Scherer, S. W. (2010). Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder.Journal of Medical Genetics, 47(3), 195–203. https://doi.org/10.1136/jmg.2009.069369
  • Fernández-Urquiza, M., Diez-Itza, E., & Cortiñas, S. (2017). PREP-CORP: Sistema de etiquetado pragmático de corpus clínicos de Lengua oral [PREP-CORP: PRagmatic Evaluation Protocol for the analysis of oral CORPora from clinical populations].In M. C. Fernández López, M. Martí Sánchez, & A. M. Ruiz Martínez (Eds.), Aplicaciones de la lingüística (pp. 167–183). Universidad de Alcalá.
  • Fernández-Urquiza, M., Viejo, A., Cortiñas, S., Huelmo, J., Medina, B., García, I., & Diez-Itza, E. (2015). Perfiles pragmáticos comparados de síndromes genéticos neuroevolutivos (síndrome de Williams, síndrome de down y síndrome de X Frágil) [Pragmatic profiles of neurodevelopmental syndromes with a genetic basis (Williams syndrome, Down syndrome, and Fragile-X syndrome)].In F. Diéguez-Vide (Ed.), Temas de lingüística clínica (pp. 89–90). Horsori Editorial.
  • Fidler, D. J., Lunkenheimer, E., & Hahn, L. (2011). Emerging behavioral phenotypes and dynamic systems theory.International Review of Research in Developmental Disabilities, 40, 17–42. https://doi.org/10.1016/B978-0-12-374478-4.00002-2
  • Gallardo-Paúls, B. (2005). Categorías inferenciales en pragmática clínica.Revista de Neurologia [Inferential categories in clinical pragmatics], 41(Suppl. 1), 65–71. https://doi.org/10.33588/rn.41S01.2005373
  • Ganz, J. B., & Simpson, R. L. (2004). Effects on communicative requesting and speech development of the Picture Exchange Communication System in children with characteristics of autism.Journal of Autism and Developmental Disorders, 34(4), 395–409. https://doi.org/10.1023/b:jadd.0000037416.59095.d7
  • Ghebranious, N., Giampietro, P. F., Wesbrook, F. P., & Rezkalla, S. H. (2007). A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation.American Journal of Medical Genetics Part A, 143A(13), 1462–1471. https://doi.org/10.1002/ajmg.a.31837
  • Giaroli, G., Bass, N., Strydom, A., Rantell, K., & McQuillin, A. (2014). Does rare matter? Copy number variants at 16p11.2 and the risk of psychosis: A systematic review of literature and meta-analysis.Schizophrenia Research, 159(2–3), 340–346. https://doi.org/10.1016/j.schres.2014.09.025
  • Goldenberg, P. (2018). An update on common chromosome microdeletion and microduplication syndromes.Pediatric Annals, 47(5), e198–e203. https://doi.org/10.3928/19382359-20180419-01
  • Grice, H. P. (1975). Logic and conversation.In J. Cole & P. Morgan (Eds.), Syntax and semantics volume 3: Speech acts (pp. 41–58). Academic Press.
  • Guha, S., Rees, E., Darvasi, A., Ivanov, D., Ikeda, M., Bergen, S. E., Magnusson, P. K., Cormican, P., Morris, D., Gill, M., Cichon, S., Rosenfeld, J. A., Lee, A., Gregersen, P. K., Kane, J. M., Malhotra, A. K., Rietschel, M., Nöthen, M. M., Degenhardt, F., & Wellcome Trust Case Control Consortium 2. (2013). Implication of a rare deletion at distal 16p11.2 in schizophrenia.JAMA Psychiatry, 70(3), 253–260. https://doi.org/10.1001/2013.jamapsychiatry.71
  • Hanson, 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., Chen, Q., D'Angelo, D., Moreno-de-Luca, A., Orr, P. T., Boomer, K. B., Evans, D. W., Kanne, S., Berry, L., Miller, F. K., & Chungm, W. K. (2015). The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population.Biological Psychiatry, 77(9), 785–793. https://doi.org/10.1016/j.biopsych.2014.04.021
  • Hanson, E., Nasir, R. H., Fong, A., Lian, A., Hundley, R., Shen, Y., Wu, B. L., Holm, I. A., Miller, D. T., & 16p11.2 Study Group Clinicians. (2010). Cognitive and behavioral characterization of 16p11.2 deletion syndrome.Journal of Developmental and Behavioral Pediatrics, 31(8), 649–657. https://doi.org/10.1097/DBP.0b013e3181ea50ed
  • Hempel, M., Rivera Brugués, N., Wagenstaller, J., Lederer, G., Weitensteiner, A., Seidel, H., Meitinger, T., & Strom, T. M. (2009). Microdeletion syndrome 16p11.2-p12.2: Clinical and molecular characterization.American Journal of Medical Genetics Part A, 149A(10), 2106–2112. https://doi.org/10.1002/ajmg.a.33042
  • Hippolyte, L., Maillard, A. M., Rodriguez-Herreros, B., Pain, A., Martin-Brevet, S., Ferrari, C., Conus, P., Macé, A., Hadjikhani, N., Metspalu, A., Reigo, A., Kolk, A., Männik, K., Barker, M., Isidor, B., le Caignec, C., Mignot, C., Schneider, L., Mottron, L., & Jacquemont, S. (2016). The number of genomic copies at the 16p11.2 locus modulates language, verbal memory, and inhibition.Biological Psychiatry, 80(2), 129–139. https://doi.org/10.1016/j.biopsych.2015.10.021
  • Jacquemont, S., Reymond, A., Zufferey, F., Harewood, L., Walters, R. G., Kutalik, Z., Martinet, D., Shen, Y., Valsesia, A., Beckmann, N. D., Thorleifsson, G., Belfiore, M., Bouquillon, S., Campion, D., de Leeuw, N., de Vries, B. B. A., Esko, T., Fernandez, B. A., Fernández-Aranda, F., & Froguel, P. (2011). Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.Nature, 478(7367), 97–102. https://doi.org/10.1038/nature10406
  • Jenkins, J., III., Chow, V., Blaskey, L., Kuschner, E., Qasmieh, S., Gaetz, L., Edgar, J. C., Mukherjee, P., Buckner, R., Nagarajan, S. S., Chung, W. K., Spiro, J. E., Sherr, E. H., Berman, J. I., & Roberts, T. P. L. (2016). Auditory evoked M100 response latency is delayed in children with 16p11.2 deletion but not 16p11.2 duplication.Cerebral Cortex, 26(5), 1957–1964. https://doi.org/10.1093/cercor/bhv008
  • Jenna, L., & Danahy, E. K. (2020). Examining social communication effects of a picture communication board in a child with autism.Perspectives of the ASHA Special Interest Groups, 5(2), 492–505. https://doi.org/10.1044/2020_PERSP-19-00113
  • Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., Gauthier, L. D., Brand, H., Solomonson, M., Watts, N. A., Rhodes, D., Singer-Berk, M., England, E. M., Seaby, E. G., Kosmicki, J. A., & MacArthur, D. G. (2020). The mutational constraint spectrum quantified from variation in 141,456 humans.Nature, 581(7809), 434–443. https://doi.org/10.1038/s41586-020-2308-7
  • Karmiloff-Smith, A. (1998). Development itself is the key to understanding developmental disorders.Trends in Cognitive Sciences, 2(10), 389–398. https://doi.org/10.1016/S1364-6613(98)01230-3
  • Ketelaars, M. P., Cuperus, J. M., van Daal, J., Jansonius, K., & Verhoeven, L. (2009). Screening for pragmatic language impairment: The potential of the children's communication checklist.Research in Developmental Disabilities, 30(5), 952–960. https://doi.org/10.1016/j.ridd.2009.01.006
  • Kim, S. H., Green-Snyder, L., Lord, C., Bishop, S., Steinman, K. J., Bernier, R., Hanson, E., Goin-Kochel, R. P., & Chung, W. K. (2020). Language characterization in 16p11.2 deletion and duplication syndromes.American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 183(6), 380–391. https://doi.org/10.1002/ajmg.b.32809
  • Klusek, J., Martin, G. E., & Losh, M. (2014). A comparison of pragmatic language in boys with autism and fragile X syndrome.Journal of Speech, Language, and Hearing Research, 57(5), 1692–1707. https://doi.org/10.1044/2014_JSLHR-L-13-0064
  • Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., Gilliam, T. C., Nowak, N. J., Cook, E. H., Jr., Dobyns, W. B., & Christian, S. L. (2008). Recurrent 16p11.2 microdeletions in autism.Human Molecular Genetics, 17(4), 628–638. https://doi.org/10.1093/hmg/ddm376
  • Laws, G., & Bishop, D. V. M. (2004). Pragmatic language impairment and social deficits in Williams syndrome: A comparison with Down's syndrome and specific language impairment.International Journal of Language & Communication Disorders, 39(1), 45–64. https://doi.org/10.1080/13682820310001615797
  • Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O'Donnell-Luria, A. H., Ware, J. S., Hill, A. J., Cummings, B. B., Tukiainen, T., Birnbaum, D. P., Kosmicki, J. A., Duncan, L. E., Estrada, K., Zhao, F., Zou, J., Pierce-Hoffman, E., Berghout, J., …Exome Aggregation Consortium. (2016). Analysis of protein-coding genetic variation in 60,706 humans.Nature, 536(7616), 285–291. https://doi.org/10.1038/nature19057
  • Luyster, R. J., Kadlec, M. B., Carter, A., & Tager-Flusberg, H. (2008). Language assessment and development in toddlers with autism spectrum disorders.Journal of Autism and Developmental Disorders, 38(8), 1426–1438. https://doi.org/10.1007/s10803-007-0510-1
  • MacWhinney, B. (2000). The CHILDES project: Tools for analyzing talk. Taylor & Francis Group.
  • Maillard, A. M., Ruef, A., Pizzagalli, F., Migliavacca, E., Hippolyte, L., Adaszewski, S., Dukart, J., Ferrari, C., Conus, P., Männik, K., Zazhytska, M., Siffredi, V., Maeder, P., Kutalik, Z., Kherif, F., Hadjikhani, N., 16p11.2 Exome Aggregation Consortium, Beckmann, J. S., Reymond, A., … Jacquemont, S. (2015). The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity.Molecular Psychiatry, 20(1), 140–147. https://doi.org/10.1038/mp.2014.145
  • Martorella, M., Barford, K., Winkler, B., & Deppmann, C. D. (2017). Emergent role of Coronin-1a in neuronal signaling.Vitamins and Hormones, 104, 113–131. https://doi.org/10.1016/bs.vh.2016.10.002
  • Mefford, H. C., Muhle, H., Ostertag, P., von Spiczak, S., Buysse, K., Baker, C., Franke, A., Malafosse, A., Genton, P., Thomas, P., Gurnett, C. A., Schreiber, S., Bassuk, A. G., Guipponi, M., Stephani, U., Helbig, I., & Eichler, E. E. (2010). Genome-wide copy number variation in epilepsy: Novel susceptibility loci in idiopathic generalized and focal epilepsies.PLoS Genetics, 6(5), Article e1000962. https://doi.org/10.1371/journal.pgen.1000962
  • Mei, C., Fedorenko, E., Amor, D. J., Boys, A., Hoeflin, C., Carew, P., Burgess, T., Fisher, S. E., & Morgan, A. T. (2018). Deep phenotyping of speech and language skills in individuals with 16p11.2 deletion.European Journal of Human Genetics, 26(5), 676–686. https://doi.org/10.1038/s41431-018-0102-x
  • Menon, S., Goldfarb, D., Ho, C. T., Cloer, E. W., Boyer, N. P., Hardie, C., Bock, A. J., Johnson, E. C., Anil, J., Major, M. B., & Gupton, S. L. (2021). The TRIM9/TRIM67 neuronal interactome reveals novel activators of morphogenesis.Molecular Biology of the Cell, 32(4), 314–330. https://doi.org/10.1091/mbc.E20-10-0622
  • Millar, D. C., Light, J. C., & Schlosser, R. W. (2006). The impact of augmentative and alternative communication intervention on the speech production of individuals with developmental disabilities: A research review.Journal of Speech, Language, and Hearing Research, 49(2), 248–264. https://doi.org/10.1044/1092-4388(2006/021)
  • Monfort, M., & Juárez, A. (2006). La práctica de la comunicación bimodal [Bimodal communication]. Entha Ediciones.
  • Monfort, M., & Sánchez, A. J. (1988). Registro Fonológico Inducido [Elicited Phonological Register].Revista de Logopedia, Foniatría y Audiología, 8(2), 88–96. https://doi.org/10.1016/S0214-4603(88)75430-3
  • Mullen, S. A., Carvill, G. L., Bellows, S., Bayly, M. A., Berkovic, S. F., Dibbens, L. M., Scheffer, I. E., & Mefford, H. C. (2013). Copy number variants are frequent in genetic generalized epilepsy with intellectual disability.Neurology, 81(17), 1507–1514. https://doi.org/10.1212/WNL.0b013e3182a95829
  • Newborg, J., Stock, J. R., & Wnek, L. (1996). Inventario de Desarrollo Battelle. TEA Ediciones.
  • Niarchou, M., Chawner, S. J. R. A., Doherty, J. L., Maillard, A. M., Jacquemont, S., Chung, W. K., Green-Snyder, L. A., Bernier, R. A., Goin-Kochel, R. P., Hanson, E., Linden, D. E. J., Linden, S. C., Raymond, F. L., Skuse, D., Hall, J., Owen, M. J., & Van Den Bree, M. B. M. (2019). Psychiatric disorders in children with 16p11.2 deletion and duplication.Translational Psychiatry, 9(1), Article No. 8. https://doi.org/10.1038/s41398-018-0339-8
  • Norbury, C. F. (2014). Practitioner review: Social (pragmatic) communication disorder conceptualization, evidence and clinical implications.The Journal of Child Psychology and Psychiatry, 55(3), 204–216. https://doi.org/10.1111/jcpp.12154
  • Owen, J. P., Bukshpun, P., Pojman, N., Thieu, T., Chen, Q., Lee, J., D'Angelo, D., Glenn, O. A., Hunter, J. V., Berman, J. I., Roberts, T. P., Buckner, R., Nagarajan, S. S., Mukherjee, P., & Sherr, E. H. (2018). Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2.Radiology, 286(1), 217–226. https://doi.org/10.1148/radiol.2017162934
  • Owen, J. P., Chang, Y. S., Pojman, N. J., Bukshpun, P., Wakahiro, M. L. J., Marco, E. J., Berman, J. I., Spiro, J. E., Chung, W. K., Buckner, R. L., Roberts, T. P. L., Nagarajan, S. S., Sherr, E. H., & Mukherjee, P. (2014). Aberrant white matter microstructure in children with 16p11.2 deletions.Journal of Neuroscience, 34(18), 6214–6223. https://doi.org/10.1523/JNEUROSCI.4495-13.2014
  • Philofsky, A., Fidler, D. J., & Hepburn, S. (2007). Pragmatic language profiles of school-age children with autism spectrum disorders and Williams syndrome.American Journal of Speech-Language Pathology, 16(4), 368–380. https://doi.org/10.1044/1058-0360(2007/040)
  • Qureshi, A. Y., Mueller, S., Snyder, A. Z., Mukherjee, P., Berman, J. I., Roberts, T. P. L., Nagarajan, S. S., Spiro, J. E., Chung, W. K., Sherr, E. H., & Buckner, R. L. (2014). Opposing brain differences in 16p11.2 deletion and duplication carriers.Journal of Neuroscience, 34(34), 11199–11211. https://doi.org/10.1523/JNEUROSCI.1366-14.2014
  • Raca, G., Baas, B. S., Kirmani, S., Laffin, J. J., Jackson, C. A., Strand, E. A., Jakielski, K. J., & Shriberg, L. D. (2013). Childhood apraxia of speech (CAS) in two patients with 16p11.2 microdeletion syndrome.European Journal of Human Genetics, 21(4), 455–459. https://doi.org/10.1038/ejhg.2012.165
  • Rice, M. L., Smolik, F., Perpich, D., Thompson, T., Rytting, N., & Blossom, M. (2010). Mean length of utterance levels in 6-month intervals for children 3 to 9 years with and without language impairments.Journal of Speech, Language, and Hearing Research, 53(2), 333–349. https://doi.org/10.1044/1092-4388(2009/08-0183)
  • Rosenfeld, J. A., Coppinger, J., Bejjani, B. A., Girirajan, S., Eichler, E. E., Shaffer, L. G., & Ballif, B. C. (2010). Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications.Journal of Neurodevelopmental Disorders, 2(1), 26–38. https://doi.org/10.1007/s11689-009-9037-4
  • Ruffman, T., Garnham, W., & Rideout, P. (2001). Social understanding in autism: Eye gaze as a measure of core insights.The Journal of Child Psychology and Psychiatry, 42(8), 1083–1094. https://doi.org/10.1111/1469-7610.00807
  • Rutter, M., Bailey, A., & Lord, C. (2003). SCQ: Social Communication Questionnaire. Western Psychological Services.
  • Sacks, H., Schegloff, E. A., & Jefferson, G. (1974). A simplest systematics for the organization of turn-taking for conversation.Language, 50(4), 696–735. https://doi.org/10.2307/412243
  • Samocha, K. E., Robinson, E. B., Sanders, S. J., Stevens, C., Sabo, A., McGrath, L. M., Kosmicki, J. A., Rehnström, K., Mallick, S., Kirby, A., Wall, D. P., MacArthur, D. G., Gabriel, S. B., DePristo, M., Purcell, S. M., Palotie, A., Boerwinkle, E., Buxbaum, J. D., Cook, E. H., Jr., … Daly, M. J. (2014). A framework for the interpretation of de novo mutation in human disease.Nature Genetics, 46(9), 944–950. https://doi.org/10.1038/ng.3050
  • Santos, P. D. A., Bordini, D., Scattolin, M., Asevedo, G. R. D. C., Caetano, S. C., Paula, C. S., Perissinoto, J., & Tamanaha, A. C. (2021). O impacto da implementação do Picture Exchange Communication System—PECS na compreensão de instruções em crianças com Transtorno do Espectro do Autismo [The use of the Picture Exchange Communication System—PECS to improve verbal commands addressed to children with autism spectrum disorder].CoDAS, 33(2), Article e20200041. https://doi.org/10.1590/2317-1782/20202020041
  • Schaaf, C. P., Goin-Kochel, R. P., Nowell, K. P., Hunter, J. V., Aleck, K. A., Cox, S., Patel, A., Bacino, C. A., & Shinawi, M. (2011). Expanding the clinical spectrum of the 16p11.2 chromosomal rearrangements: Three patients with syringomyelia.European Journal of Human Genetics, 19(2), 152–156. https://doi.org/10.1038/ejhg.2010.168
  • Scheffer, I. E., Grinton, B. E., Heron, S. E., Kivity, S., Afawi, Z., Iona, X., Goldberg-Stern, H., Kinali, M., Andrews, I., Guerrini, R., Marini, C., Sadleir, L. G., Berkovic, S. F., & Dibbens, L. M. (2012). PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures.Neurology, 79(21), 2104–2108. https://doi.org/10.1212/WNL.0b013e3182752c6c
  • Schlosser, R. W. (2003). The efficacy of augmentative and alternative communication. Elsevier.
  • Semel, E., Wayne, W., & Secord, A. (2006). Clinical Evaluation of Language Fundamentals. Spanish Edition (CELF-4). Psychological Corporation.
  • Shimojima, K., Inoue, T., Fujii, Y., Ohno, K., & Yamamoto, T. (2009). A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and hemivertebrae.European Journal of Medical Genetics, 52(6), 433–435. https://doi.org/10.1016/j.ejmg.2009.09.007
  • 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., Clark, G., Lee, J., Proud, M., Stocco, A., Rodriguez, D. L., Kozel, B. A., Sparagana, S., Roeder, E. R., McGrew, S. G., … Lupski, J. R. (2010). Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size.Journal of Medical Genetics, 47(5), 332–341. https://doi.org/10.1136/jmg.2009.073015
  • Shiow, L. R., Roadcap, D. W., Paris, K., Watson, S. R., Grigorova, I. L., Lebet, T., An, J., Xu, Y., Jenne, C. N., Föger, N., Sorensen, R. U., Goodnow, C. C., Bear, J. E., Puck, J. M., & Cyster, J. G. (2008). The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency.Nature Immunology, 9(11), 1307–1315. https://doi.org/10.1038/ni.1662
  • Shiro, M., Diez-Itza, E., & Fernández-Urquiza, M. (2019). Evaluative language and component structure of oral narratives in Williams syndrome.In E. Aguilar Mediavilla, L. Buil-Legaz, R. López-Penadés, V. A. Sánchez-Azanza, & D. Adrover-Roig (Eds.), Atypical language development in romance languages (pp. 235–252). John Benjamins. https://doi.org/10.1075/z.223.14shi
  • Stefansson, H., Meyer-Lindenberg, A., Steinberg, S., Magnusdottir, B., Morgen, K., Arnarsdottir, S., Bjornsdottir, G., Walters, G. B., Jonsdottir, G. A., Doyle, O. M., Tost, H., Grimm, O., Kristjansdottir, S., Snorrason, H., Davidsdottir, S. R., Gudmundsson, L. J., Jonsson, G. F., Stefansdottir, B., Helgadottir, I., & Stefansson, K. (2014). CNVs conferring risk of autism or schizophrenia affect cognition in controls.Nature, 505(7483), 361–366. https://doi.org/10.1038/nature12818
  • Steinman, K. J., Spence, S. J., Ramocki, M. B., Proud, M. B., Kessler, S. K., Marco, E. J., Green Snyder, L. A., D'Angelo, D., Chen, Q., Chung, W. K., Sherr, E. H., & on behalf of the Simons VIP Consortium. (2016). 16p11.2 deletion and duplication: Characterizing neurologic phenotypes in a large clinically ascertained cohort.American Journal of Medical Genetics Part A, 170(11), 2943–2955. https://doi.org/10.1002/ajmg.a.37820
  • Swineford, L. B., Thurm, A., Baird, G., Wetherby, A. M., & Swedo, S. (2014). Social (pragmatic) communication disorder: A research review of this new DSM-5 diagnostic category.Journal of Neurodevelopmental Disorders, 6(1), 41. https://doi.org/10.1186/1866-1955-6-41
  • Szelest, M., Stefaniak, M., Ręka, G., Jaszczuk, I., & Lejman, M. (2021). Three case reports of patients indicating the diversity of molecular and clinical features of 16p11.2 microdeletion anomaly.BMC Medical Genomics, 14(1), 76. https://doi.org/10.1186/s12920-021-00929-8
  • Tager-Flusberg, H. (2007). Evaluating the theory-of-mind hypothesis of autism.Current Directions in Psychological Science, 16(6), 311–315. https://doi.org/10.1111/j.1467-8721.2007.00527.x
  • Tager-Flusberg, H., Rogers, S., Cooper, J., Landa, R., Lord, C., Paul, R., Rice, M., Stoel-Gammon, C., Wetherby, A., & Yoder, P. (2009). Defining spoken language benchmarks and selecting measures of expressive language development for young children with autism spectrum disorders.Journal of Speech, Language, and Hearing Research, 52(3), 643–652. https://doi.org/10.1044/1092-4388(2009/08-0136)
  • Topal, Z., Demir Samurcu, N., Taskiran, S., Tufan, A. E., & Semerci, B. (2018). Social communication disorder: A narrative review on current insights.Neuropsychiatric Disease and Treatment, 14, 2039–2046. https://doi.org/10.2147/NDT.S121124
  • Van Den Heuvel, E., Manders, E., Swillen, A., & Zink, I. (2016). Developmental trajectories of structural and pragmatic language skills in school-aged children with Williams syndrome.Journal of Intellectual Disability Research, 60(10), 903–919. https://doi.org/10.1111/jir.12329
  • Volden, J., Coolican, J., Garon, N., White, J., & Bryson, S. (2009). Brief report: Pragmatic language in autism spectrum disorder: Relationships to measures of ability and disability.Journal of Autism and Developmental Disorders, 39(2), 388–393. https://doi.org/10.1007/s10803-008-0618-y
  • Walker, M. (1987, March, 29–April). The Makaton vocabulary: Uses and effectiveness [Conference paper]. International Afasic Symposium of Specific and Language Disorders in Children, Reading, United Kingdom. https://files.eric.ed.gov/fulltext/ED291193.pdf
  • Walsh, K. M., & Bracken, M. B. (2011). Copy number variation in the dosage-sensitive 16p11.2 interval accounts for only a small proportion of autism incidence: A systematic review and meta-analysis.Genetics in Medicine, 13(5), 377–384. https://doi.org/10.1097/GIM.0b013e3182076c0c
  • Walters, R. G., Jacquemont, S., Valsesia, A., De Smith, A. J., Martinet, D., Andersson, J., Falchi, M., Chen, F., Andrieux, J., Lobbens, S., Delobel, B., Stutzmann, F., El-Sayed Moustafa, J. S., Chèvre, J.-C., Lecoeur, C., Vatin, V., Bouquillon, S., Buxton, J. L., Boute, O., … Beckmann, J. S. (2010). A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.Nature, 463(7281), 671–675. https://doi.org/10.1038/nature08727
  • Wechsler, D. (2015). Escala de Inteligencia de Wechsler Para Niños-V (WISC-V) [Wechsler Intelligence Scale for Children–Fifth Edition (WISC-V)]. Pearson.
  • Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., Platt, O. S., Ruderfer, D. M., Walsh, C. A., Altshuler, D., Chakravarti, A., Tanzi, R. E., Stefansson, K., Santangelo, S. L., Gusella, J. F., …for the Autism Consortium. (2008). Association between microdeletion and microduplication at 16p11. 2 and autism.New England Journal of Medicine, 358(7), 667–675. https://doi.org/10.1056/NEJMoa075974
  • Wimmer, H., & Perner, J. (1983). Beliefs about beliefs: Representation and constraining function of wrong beliefs in young children's understanding of deception.Cognition, 13(1), 103–128. https://doi.org/10.1016/0010-0277(83)90004-5
  • Zufferey, F., Sherr, E. H., Beckmann, N. D., Hanson, E., Maillard, A. M., Hippolyte, L., Macé, A., Ferrari, C., Kutalik, Z., Andrieux, J., Aylward, E., Barker, M., Bernier, R., Bouquillon, S., Conus, P., Delobel, B., Faucett, W. A., Goin-Kochel, R. P., Grant, E., …on behalf of the 16p11.2 European Consortium Simons VIP Consortium. (2012). A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders.Journal of Medical Genetics, 49(10), 660–668. https://doi.org/10.1136/jmedgenet-2012-101203

Additional Resources