Genetic Studies of Language Disorders

Developmental language disorder (DLD) is estimated to affect 8 per cent of primary school-aged children, and has lasting impacts on academic achievement and social-emotional and behavioural outcomes. DLD is classified as a severe and persistent impairment in the acquisition, understanding, production or use of language, occurring in the absence of comorbid neurodevelopmental disorder. The phenotype of DLD is well established, yet there is relatively limited understanding of its aetiology. A complex interaction of genetic variants and environmental factors is thought to be the cause. To date, linkage and association analyses have implicated a handful of genes in DLD populations, including CMIP and ATP2C2. While many of these variants are common in DLD, they are not consistently associated with severe language impairment, and many overlap with chromosome regions commonly associated with neurodevelopmental disorders such as intellectual disability. The effects of alternate genetic models such as copy number and rare variants may provide a gateway to understanding the complex genetic pathways of this disorder. Pleiotropy and generalisation are also important considerations in understanding the genetic architecture of DLD. Here we outline the phenotype of DLD and provide an overview of recently identified gene pathways implicated in this disorder.

Keywords

language language disorder genetics genes population genetics phenotype environment child

Information

Type: Chapter
Information: Language Development
Individual Differences in a Social Context
, pp. 45 - 77
DOI: https://doi.org/10.1017/9781108643719.005 [Opens in a new window]
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Alarcon, M., Abrahams, B. S., Stone, J. L., Duvall, J. A., Perederiy, J. V., Bomar, J. M., … Geschwind, D. H. (2008). Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. American Journal of Human Genetics, 82(1), 150–159. doi:10.1016/j.ajhg.2007.09.005CrossRef Google Scholar PubMed

American Speech-Language-Hearing Association (ASHA). (2007). Ad Hoc Committee on Childhood Apraxia of Speech. Rockville (MD). www.asha.org/policy/PS2007-00277/Google Scholar

Arking, D. E., Cutler, D. J., Brune, C. W., Teslovich, T. M., West, K., Ikeda, M., … Chakravarti, A. (2008). A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. American Journal of Human Genetics, 82(1), 160–164. doi:10.1016/j.ajhg.2007.09.015Google Scholar

Bacon, C., & Rappold, G. A. (2012). The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders. Human Genetics, 131(11), 1687–1698. doi:10.1007/s00439-012-1193-zCrossRef Google Scholar PubMed

Barnett, C. P., & Van Bon, B. W. (2015). Monogenic and chromosomal causes of isolated speech and language impairment. Journal of Medical Genetics, 52(11), 719–729. doi:10.1136/jmedgenet-2015-103161Google Scholar

Bartlett, C. W., Flax, J. F., Logue, M. W., Vieland, V. J., Bassett, A. S., Tallal, P., & Brzustowicz, L. M. (2002). A major susceptibility locus for specific language impairment is located on 13q21. American Journal of Human Genetics, 71(1), 45–55. doi:10.1086/341095Google Scholar

Beckmann, J. S., Estivill, X., & Antonarakis, S. E. (2007). Copy number variants and genetic traits: Closer to the resolution of phenotypic to genotypic variability. Nature Reviews Genetics, 8(8), 639–646. doi:10.1038/nrg2149Google Scholar

Beitchman, J. H., Brownlie, E. B., & Bao, L. (2014). Age 31 mental health outcomes of childhood language and speech disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 53(10), 1102–1110. doi:10.1016/j.jaac.2014.07.006CrossRef Google Scholar PubMed

Bishop, D. V. M., North, T., & Donlan, C. (1995). Genetic basis of specific language impairment: Evidence from a twin study. Developmental Medicine & Child Neurology, 37(1), 56–71. doi:10.1111/j.1469-8749.1995.tb11932.xGoogle Scholar

Bishop, D. V. M., Snowling, M. J., Thompson, P. A., & Greenhalgh, T. (2016). CATALISE: A multinational and multidisciplinary Delphi consensus study: Identifying language impairments in children. PLoS ONE, 11(7). doi:10.1371/journal.pone.0158753CrossRef Google Scholar PubMed

Bishop, D. V. M., Snowling, M. J., Thompson, P. A., & Greenhalgh, T. (2017). Phase 2 of CATALISE: A multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology. Journal of Child Psychology and Psychiatry, 58(10), 1068–1080. doi:10.1111/jcpp.12721Google Scholar

Blair, D. R., Lyttle, C. S., Mortensen, J. M., Bearden, C. F., Jensen, A. B., Khiabanian, H., … Rzhetsky, A. (2013). A nondegenerate code of deleterious variants in mendelian loci contributes to complex disease risk. Cell, 155(1), 70–80. doi:10.1016/j.cell.2013.08.030Google Scholar

Border, R., Johnson, E. C., Evans, L. M., Smolen, A., Berley, N., Sullivan, P. F., & Keller, M. C. (2019). No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. American Journal of Psychiatry, 176(5), 376–387. doi:10.1176/appi.ajp.2018.18070881CrossRef Google Scholar PubMed

Bretherton, L., Prior, M., Bavin, E., Cini, E., Eadie, P., & Reilly, S. (2014). Developing relationships between language and behaviour in preschool children from the Early Language in Victoria Study: Implications for intervention. Emotional and Behavioural Difficulties, 19(1), 7–27. doi:10.1080/13632752.2013.854956Google Scholar

Brignell, A., Williams, K., Jachno, K., Prior, M., Reilly, S., & Morgan, A. T. (2018). Patterns and predictors of language development from 4 to 7 years in verbal children with and without Autism Spectrum Disorder. Journal of Autism and Developmental Disorders, 10, 3282–3295. doi:10.1007/s10803-018-3565-2CrossRef Google Scholar

Carrion-Castillo, A., Van Bergen, E., Vino, A., Van Zuijen, T., de Jong, P. F., Francks, C., & Fisher, S. E. (2016). Evaluation of results from genome-wide studies of language and reading in a novel independent dataset. Genes, Brain and Behavior, 15(6), 531–541. doi:10.1111/gbb.12299Google Scholar

Catroppa, C., & Anderson, V. (2004). Recovery and predictors of language skills two years following pediatric traumatic brain injury. Brain and Language, 88(1), 68–78. doi:10.1016/S0093-934X(03)00159-7CrossRef Google Scholar PubMed

Catts, H. W., Adlof, S. M., Hogan, T. P., & Weismer, S. E. (2005). Are specific language impairment and dyslexia distinct disorders? Journal of Speech, Language, and Hearing Research, 48(6), 1378–1396. doi:10.1044/1092-4388(2005/096)Google Scholar

Centanni, T. M., Green, J. R., Iuzzini-Seigel, J., Bartlett, C. W., & Hogan, T. P. (2015). Evidence for the multiple hits genetic theory for inherited language impairment: A case study. Frontiers in Genetics, 6, 272. doi:10.3389/fgene.2015.00272Google Scholar

Chen, X. S., Reader, R. H., Hoischen, A., Veltman, J. A., Simpson, N. H., Francks, C., … Fisher, S. E. (2017). Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment. Scientific Reports, 7, 46105. doi:10.1038/srep46105Google Scholar

Clegg, J., Hollis, C., Mawhood, L., & Rutter, M. (2005). Developmental language disorders – a follow-up in later adult life. Cognitive, language and psychosocial outcomes. Journal of Child Psychology and Psychiatry, 46(2), 128–149. doi:10.1111/j.1469-7610.2004.00342.xGoogle Scholar

Cleland, J., Wood, S., Hardcastle, W., Wishart, J., & Timmins, C. (2010). Relationship between speech, oromotor, language and cognitive abilities in children with Down’s syndrome. International Journal of Language & Communication Disorders, 45(1), 83–95. doi:10.3109/13682820902745453Google Scholar

Coe, B. P., Witherspoon, K., Rosenfeld, J. A., van Bon, B. W. M., Vulto-van Silfhout, A. T., Bosco, P., … Eichler, E. E. (2014). Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nature Genetics, 46(10), 1063–1071. doi:10.1038/ng.3092Google Scholar

Constantino, J. N. (2018). Deconstructing autism: From unitary syndrome to contributory developmental endophenotypes. International Review of Psychiatry, 30(1), 18–24. doi:10.1080/09540261.2018.1433133Google Scholar

Conti-Ramsden, G., Botting, N., Simkin, Z., & Knox, E. (2001). Follow-up of children attending infant language units: Outcomes at 11 years of age. International Journal of Language & Communication Disorders, 36(2), 207–219. doi:10.1080/1368282012121313682820902745453Google Scholar

Dale, P. S., Simonoff, E., Bishop, D. V., Eley, T. C., Oliver, B., Price, T. S., … Plomin, R. (1998). Genetic influence on language delay in two-year-old children. Nature Neuroscience, 1(4), 324–328. doi:10.1038/1142CrossRef Google Scholar PubMed

Devanna, P., Chen, X. S., Ho, J., Gajewski, D., Smith, S. D., Gialluisi, A., … Vernes, S. C. (2017). Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders. Molecular Psychiatry, 23(5), 1375–1384. doi:10.1038/mp.2017.30Google Scholar

Docking, K., Munro, N., Marshall, T., & Togher, L. (2016). Narrative skills of children treated for brain tumours: The impact of tumour and treatment related variables on microstructure and macrostructure. Brain Injury, 30(8), 1005–1018. doi:10.3109/02699052.2016.1147602Google Scholar

Eadie, P., Conway, L., Hallenstein, B., Mensah, F. K., McKean, C., & Reilly, S. (2018). Quality of life in children with developmental language disorder. International Journal of Language & Communication Disorders, 53(4), 799–810. doi:10.1111/1460-6984.12385Google Scholar

Eadie, P., Morgan, A. T., Ukoumunne, O. C., Ttofari Eecen, K., Wake, M., & Reilly, S. (2015). Speech sound disorder at 4 years: Prevalence, comorbidities, and predictors in a community cohort of children. Developmental Medicine & Child Neurology, 57(6), 578–584. doi:10.1111/dmcn.12635Google Scholar

Eeles, R. A., Kote-Jarai, Z., Giles, G. G., Al Olama, A. A., Guy, M., Jugurnauth, S. K., … Easton, D. F. (2008). Multiple newly identified loci associated with prostate cancer susceptibility. Nature Genetics, 40(3), 316–321. doi:10.1038/ng.90Google Scholar

Eicher, J. D., Powers, N. R., Miller, L. L., Akshoomoff, N., Amaral, D. G., Bloss, C. S., … Gruen, J. R. (2013). Genome-wide association study of shared components of reading disability and language impairment. Genes, Brain and Behavior, 12(8), 792–801. doi:10.1111/gbb.12085Google Scholar

Eising, E., Carrion-Castillo, A., Vino, A., Strand, E. A., Jakielski, K. J., Scerri, T. S., … Fisher, S. E. (2018). A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development. Molecular Psychiatry, 24, 1065–1078. doi:10.1038/s41380-018-0020-xGoogle Scholar

Ercan-Sencicek, A. G., Davis Wright, N. R., Sanders, S. J., Oakman, N., Valdes, L., Bakkaloglu, B., … Grigorenko, E. L. (2012). A balanced t(10;15) translocation in a male patient with developmental language disorder. European Journal of Medical Genetics, 55(2), 128–131. doi:10.1016/j.ejmg.2011.12.005Google Scholar

Estruch, S. B., Graham, S. A., Deriziotis, P., & Fisher, S. E. (2016). The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers. Scientific Reports, 6, 20911 doi:10.1038/srep20911Google Scholar

Evans, P. D., Mueller, K. L., Gamazon, E. R., Cox, N. J., & Tomblin, J. B. (2015). A genome-wide sib-pair scan for quantitative language traits reveals linkage to chromosomes 10 and 13. Genes, Brain and Behavior, 14(5), 387–397. doi:10.1111/gbb.12223CrossRef Google Scholar PubMed

Ewing-Cobbs, L., & Barnes, M. (2002). Linguistic outcomes following traumatic brain injury in children. Seminars in Pediatric Neurology, 9(3), 209–217. doi:10.1053/spen.2002.35502Google Scholar

Falcaro, M., Pickles, A., Newbury, D. F., Addis, L., Banfield, E., Fisher, S. E., … SLI Consortium. (2008). Genetic and phenotypic effects of phonological short‐term memory and grammatical morphology in specific language impairment. Genes, Brain and Behavior, 7(4), 393–402. doi:10.1111/j.1601-183X.2007.00364.xGoogle Scholar

Fedorenko, E., Morgan, A., Murray, E., Cardinaux, A., Mei, C., Tager-Flusberg, H., … 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. doi:10.1038/ejhg.2015.149CrossRef Google Scholar PubMed

Feuk, L., Kalervo, A., Lipsanen-Nyman, M., Skaug, J., Nakabayashi, K., Finucane, B., … Hannula-Jouppi, K. (2006). Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia. American Journal of Human Genetics, 79(5), 965–972 doi:10.1086/508902Google Scholar

Fisher, S. E., & Scharff, C. (2009). FOXP2 as a molecular window into speech and language. Trends in Genetics, 25(4), 166–177. doi:10.1016/j.tig.2009.03.002Google Scholar

Franic, S., Groen-Blokhuis, M. M., Dolan, C. V., Kattenberg, M. V., Pool, R., Xiao, X., … Boomsma, D. I. (2015). Intelligence: Shared genetic basis between Mendelian disorders and a polygenic trait. European Journal of Human Genetics, 23(10), 1378–1383 doi:10.1038/ejhg.2015.3Google Scholar

Gialluisi, A., Andlauer, T. F. M., Mirza-Schreiber, N., Moll, K., Becker, J., Hoffmann, P., … Schulte-Körne, G. (2019). Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia. Translational Psychiatry, 9(77), 1–77. doi:10.1038/s41398-019-0402-0CrossRef Google Scholar PubMed

Gialluisi, A., Newbury, D. F., Wilcutt, E. G., Olson, R. K., DeFries, J. C., Brandler, W. M., … Fisher, S. E. (2014). Genome-wide screening for DNA variants associated with reading and language traits. Genes, Brain and Behavior, 13(7), 686–701. doi:10.1111/gbb.12158Google Scholar

Graham, S. A., & Fisher, S. E. (2013). Decoding the genetics of speech and language. Current Opinions in Neurobiology, 23(1), 43–51. doi:10.1016/j.conb.2012.11.006CrossRef Google Scholar PubMed

Grove, J., Ripke, S., Als, T. D., Mattheisen, M., Walters, R. K., Won, H., & Børglum, A. D. (2019). Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 51(3), 431–444. doi:10.1038/s41588-019-0344-8Google Scholar

Gunasekara, C. J., Scott, C. A., Laritsky, E., Baker, M. S., MacKay, H., Duryea, J. D., … Waterland, R. A. (2019). A genomic atlas of systemic interindividual epigenetic variation in humans. Genome Biology, 20(1), 105–116. doi:10.1186/s13059-019-1708-1Google Scholar

Haarbauer-Krupa, J., King, T. Z., Wise, J., Gillam, S., Trapani, J., Weissman, B., & DePompei, R. (2019). Early elementary school outcome in children with a history of traumatic brain injury before age 6 years. The Journal of Head Trauma Rehabilitation, 34(2), 111–121. doi:10.1097/HTR.0000000000000414Google Scholar

Hamdan, F. F., Daoud, H., Rochefort, D., Piton, A., Gauthier, J., Langlois, M., … Michaud, J. L. (2010). De novo mutations in foxp1 in cases with intellectual disability, autism, and language impairment. American Journal of Human Genetics, 87(8), 671–678. doi:10.1016/j.ajhg.2010.09.017Google Scholar

Harlaar, N., Meaburn, E. L., Hayiou-Thomas, M. E., Wellcome Trust Case Control Consortium, Davis, O. S., Docherty, S., … Plomin, R. (2014). Genome-wide association study of receptive language ability of 12-year-olds. Journal of Speech Language and Hearing Research, 57(1), 96–105. doi:10.1044/1092-4388(2013/12-0303)CrossRef Google Scholar PubMed

Hayiou-Thomas, M. E., Oliver, B., & Plomin, R. (2005). Genetic influences on specific versus nonspecific language impairment in 4-year-old twins. Journal of Learning Disabilities, 38(3), 222–232. doi:10.1177/00222194050380030401Google Scholar

Heijmans, B. T., Tobi, E. W., Stein, A. D., Putter, H., Blauw, G. J., Susser, E. S., … Lumey, L. H. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceeding of the National Academy of Science USA, 105(44), 17046–17049. doi:10.1073/pnas.0806560105Google Scholar

Horn, D., Kapeller, J., Rivera-Brugués, N., Moog, U., Lorenz-Depiereux, B., Eck, S., … Strom, T. M. (2010). Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Human Mutation, 31(11), e1851–1860. doi:10.1002/humu.21362Google Scholar

Kalnak, N., Stamouli, S., Peyrard-Janvid, M., Rabkina, I., Becker, M., Klingberg, T., … Tammimies, K. (2018). Enrichment of rare copy number variation in children with developmental language disorder. Clinical Genetics, 94(3–4), 313–320. doi:10.1111/cge.13389Google Scholar

Koolen, D. A, Vissers, L. E., Nillesen, W., Smeets, D., van Ravenswaaij, C. M., Sistermans, E. A., … de Vries, B. B. (2004). A novel microdeletion, del(2)(q22.3q23.3) in a mentally retarded patient, detected by array-based comparative genomic hybridization. Clinical Genetics, 65(5), 429–429. doi:10.1111/j.0009-9163.2004.00245.xGoogle Scholar

Kornilov, S. A., Rakhlin, N., Koposov, R., Lee, M., Yrigollen, C., Caglayan, A. O., … Grigorenko, E. L. (2016). Genome-wide association and exome sequencing study of language disorder in an isolated population. Pediatrics, 137(4), e20152469. doi:10.1542/peds.2015-2469Google Scholar

Kraft, S. J., & DeThorne, L. S. (2014). The brave new world of epigenetics: Embracing complexity in the study of speech and language disorders. Current Developmental Disorders Reports, 1(3), 207–214. doi:10.1007/s40474-014-0024-4Google Scholar

Krapohl, E., Patel, H., Newhouse, S., Curtis, C. J., von Stumm, S., Dale, P. S., … Plomin, R. (2018). Multi-polygenic score approach to trait prediction. Molecular Psychiatry, 23(5), 1368–1374. doi:10.1038/mp.2017.163Google Scholar

Küpers, L. K., Monnereau, C., Sharp, G. C., Yousefi, P., Salas, L. A., Ghantous, A., … Felix, J. F. (2019). Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight. Nature Communications, 10(1), 1893–1904. doi:10.1038/s41467-019-09671-3Google Scholar

Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F., & Monaco, A. P. (2001). A forkhead-domain gene is mutated in a severe speech and language disorder. Nature, 413(6855), 519–523. doi:10.1038/35097076CrossRef Google Scholar

Lambert, J. C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., … Amouyel, P. (2009). Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nature Genetics, 41(10), 1094–1099. doi:10.1038/ng.439Google Scholar

Law, J., Mcbean, L., & Rush, R. (2011). Communication skills in a population of primary school-aged children raised in an area of pronounced social disadvantage. International Journal of Language & Communication Disorders, 46(6), 657–664. doi:10.1111/j.1460-6984.2011.00036.xGoogle Scholar

Lee, J. J., Wedow, R., Okbay, A., Kong, E., Maghzian, O., Zacher, M., … Cesarini, D. (2018). Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nature Genetics, 50(8), 1112–1121. doi:10.1038/s41588-018-0147-3CrossRef Google Scholar PubMed

Le Gall, J., Nizon, M., Pichon, O., Andrieux, J., Audebert-Bellanger, S., Baron, S., … Busa, T. (2017). Sex chromosome aneuploidies and copy-number variants: A further explanation for neurodevelopmental prognosis variability? European Journal of Human Genetics, 25(8), 930–934. doi:10.1038/ejhg.2017.93Google Scholar

Lennon, P. A., Cooper, M. L., Peiffer, D. A., Gunderson, K. L., Patel, A., Peters, S., … Bacino, C. A. (2007). Deletion of 7q31.1 supports involvement of foxp2 in language impairment: Clinical report and review. American Journal of Medical Genetics Part A, 143a(8), 791–798. doi:10.1002/ajmg.a.31632Google Scholar

Lewis, B. A., & Thompson, L. A. (1992). A study of developmental speech and language disorders in twins. Journal of Speech Hearing Research, 35(5), 1086–1094. doi:10.1044/jshr.3505.1086Google Scholar

Liégeois, F. J., Mahony, K., Connelly, A., Pigdon, L., Tournier, J. D., & Morgan, A. T. (2013). Pediatric traumatic brain injury: Language outcomes and their relationship to the arcuate fasciculus. Brain and Language, 127(3), 388–398.Google Scholar

Liégeois, F. J., Turner, S. J., Mayes, A., Bonthrone, A. F., Boys, A., Smith, L., … Morgan, A. T. (2019). Dorsal language stream anomalies in an inherited speech disorder. Brain, 142(4), 966–977.Google Scholar

Lionel, A. C., Crosbie, J., Barbosa, N., Goodale, T., Thiruvahindrapuram, B., Rickaby, J., … Scherer, S. W. (2011). Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. Science Translational Medicine, 3(95), 95ra75. doi:10.1126/scitranslmed.3002464Google Scholar

Locke, A., Ginsborg, J., & Peers, I. (2002). Development and disadvantage: Implications for the early years and beyond. International Journal of Language & Communication Disorders, 37(1), 3–15. doi:10.1080/13682820110089911Google Scholar

Lozano, R., Vino, A., Lozano, C., Fisher, S. E., & Deriziotis, P. (2015). A de novo FOXP1 variant in a patient with autism, intellectual disability and severe speech and language impairment. European Journal of Human Genetics, 23(12), 1702–1707. doi:10.1038/ejhg.2015.66Google Scholar

Luciano, M., Evans, D. M., Hansell, N. K., Medland, S. E., Montgomery, G. W., Martin, N. G., … Bates, T. C. (2013). A genome-wide association study for reading and language abilities in two population cohorts. Genes, Brain and Behavior, 12(6), 645–652. doi:10.1111/gbb.12053CrossRef Google Scholar PubMed

MacDermot, K. D., Bonora, E., Sykes, N., Coupe, A. M., Lai, C. S., Vernes, S. C., … Fisher, S. E. (2005). Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits. American Journal of Human Genetics, 76(6), 1074–1080. doi:10.1086/430841Google Scholar

McKean, C., Reilly, S., Bavin, E. L., Bretherton, L., Cini, E., Conway, L., … Mensah, F. (2017). Language outcomes at 7 years: Early predictors and co-occurring difficulties. Pediatrics, 139(3), e20161684. doi:10.1542/peds.2016-1684CrossRef Google Scholar PubMed

Mei, C., Fedorenko, E., Amor, D. J., Boys, A., Hoeflin, C., Carew, P., … 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. doi:10.1038/s41431-018-0102-xGoogle Scholar

Mei, C., Reilly, S., Reddihough, D., Mensah, F., Pennington, L., & Morgan, A. T. (2016). Language outcomes of children with cerebral palsy aged 5 years and 6 years: A population-based study. Developmental Medicine and Child Neurology, 58(6), 605–611. doi:10.1111/dmcn.12957Google Scholar

Moralli, D., Nudel, R., Chan, M. T. M., Green, C. M., Volpi, E. V., Benítez-Burraco, A., … García-Bellido, P. (2015). Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2. Molecular Cytogenetics, 8(1), 36. doi:10.1186/s13039-015-0148-1Google Scholar

Morgan, A. T., Fisher, S. E., Scheffer, I. E., & Hildebrand, M. (2017). FOXP2-related speech and language disorders. Seattle, WA: University of Washington. Available at GeneReviews®, www.ncbi.nlm.nih.gov/books/NBK368474/Google Scholar

Morgan, A. T., Mei, C., Da Costa, A., Fifer, J., Lederer, D., Benoit, V., … White, S. M. (2015). Speech and language in a genotyped cohort of individuals with Kabuki syndrome. American Journal of Medical Genetics, Part A, 167(7), 1483–1492.Google Scholar

Morgan, A. T., van Haaften, L., van Hulst, K., Edley, C., Mei, C., Tan, T. Y., … Koolen, D. A. (2018). Early speech development in Koolen de Vries syndrome limited by oral praxis and hypotonia. European Journal of Human Genetics, 26, 75–84. doi:10.1038/s41431-017-0035-9Google Scholar

Mountford, H. S., & Newbury, D. F. (2018). The genomic landscape of language: insights into evolution. Journal of Language Evolution, 3(1), 49–58. doi:10.1093/jole/lzx019Google Scholar

Newbury, D. F., Gibson, J. L., Conti-Ramsden, G., Pickles, A., Durkin, K., & Toseeb, U. (2019). Using polygenic profiles to predict variation in language and psychosocial outcomes in early and middle childhood. Journal of Speech, Language, and Hearing Research, 62, 3381–3396. epub ahead of print. doi:10.1044/2019_JSLHR-L-19-0001Google Scholar

Newbury, D. F., Mari, F., Sadighi Akha, E., MacDermot, K. D., Canitano, R., Monaco, A. P., … Knight, S. J. (2013). Dual copy number variants involving 16p11 and 6q22 in a case of childhood apraxia of speech and pervasive developmental disorder. European Journal of Human Genetics, 21(4), 361–365. doi:10.1038/ejhg.2012.166Google Scholar

Newbury, D. F., Paracchini, S., Scerri, T. S., Winchester, L., Addis, L., Richardson, A. J., … Monaco, A. P. (2011). Investigation of dyslexia and SLI risk variants in reading- and language-impaired subjects. Behavior Genetics, 41(1), 90–104. doi:10.1007/s10519-010-9424-3Google Scholar

Newbury, D. F., Winchester, L., Addis, L., Paracchini, S., Buckingham, L.-L., Clark, A., … Monaco, A. P. (2009). CMIP and ATP2C2 modulate phonological short-term memory in language impairment. American Journal of Human Genetics, 85(2), 264–272. doi:10.1016/j.ajhg.2009.07.004Google Scholar

Nicolia, V., Cavallaro, R. A., López-González, I., Maccarrone, M., Scarpa, S., Ferrer, I., & Fuso, A. (2017). DNA methylation profiles of selected pro-inflammatory cytokines in Alzheimer disease. Journal of Neuropathology & Experimental Neurology, 76(1), 27–31. doi:10.1093/jnen/nlw099Google Scholar

Nudel, R., Simpson, N. H., Baird, G., O’Hare, A., Conti-Ramsden, G., Bolton, P. F., … Newbury, D. F. (2014). Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment. Genes, Brain and Behavior, 13(4), 418–429. doi:10.1111/gbb.12127Google Scholar

O’Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., … Eichler, E. E. (2011). Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature Genetics, 43(6), 585–589. doi:10.1038/ng.835Google Scholar

Park, G., Tan, J., Garcia, G., Kang, Y., Salvesen, G., & Zhang, Z. (2016). Regulation of histone acetylation by autophagy in Parkinson disease. Journal of Biological Chemistry, 291(7), 3531–3540. doi:10.1074/jbc.M115.675488Google Scholar

Peter, B., Matsushita, M., Oda, K., & Raskind, W. (2014). De novo microdeletion of BCL11A is associated with severe speech sound disorder. American Journal of Medical Genetics Part A, 164a(8), 2091–2096. doi:10.1002/ajmg.a.36599Google Scholar

Peter, B., Raskind, W. H., Matsushita, M., Lisowski, M., Vu, T., Berninger, V. W., … Brkanac, Z. (2011). Replication of CNTNAP2 association with nonword repetition and support for FOXP2 association with timed reading and motor activities in a dyslexia family sample. Journal of Neurodevelopmental Disorders, 3(1), 39–49. doi:10.1007/s11689-010-9065-0CrossRef Google Scholar

Raca, G., Baas, B. S., Kirmani, S., Laffin, J. J., Jackson, C. A., Strand, E. A., … 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 doi:10.1038/ejhg.2012.165Google Scholar

Reader, R. H., Covill, L. E., Nudel, R., & Newbury, D. F. (2014). Genome-wide studies of specific language impairment. Current Behavioral Neuroscience Reports, 1(4), 242–250. doi:10.1007/s40473-014-0024-zCrossRef Google Scholar PubMed

Reilly, S., Tomblin, B., Law, J., McKean, C., Mensah, F. K., Morgan, A. T., … Wake, M. (2014). Specific language impairment: A convenient label for whom? International Journal of Language & Communication Disorders, 49(4), 416–451. doi:10.1111/1460-6984.12102Google Scholar

Reilly, S., Wake, M., Bavin, E. L., Prior, M., Williams, J., Bretherton, L., … Ukoumunne, O. C. (2007). Predicting language at 2 years of age: A prospective community study. Pediatrics, 120(6), 1441–1449. doi:10.1542/peds.2007-0045Google Scholar

Reilly, S., Wake, M., Ukoumunne, O. C., Bavin, E., Prior, M., Cini, E., … Bretherton, L. (2010). Predicting language outcomes at 4 years of age: Findings from the Early Language in Victoria Study. Pediatrics, 126(6), 1530–1537. doi:10.1542/peds.2010-0254Google Scholar

Reuter, M. S., Riess, A., Moog, U., Briggs, T. A., Chandler, K. E., Rauch, A., … Zweier, C. (2017). FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum. Journal of Medical Genetics, 54(1), 64–72. doi:10.1136/jmedgenet-2016-104094Google Scholar

Rice, M. L. (2012). Toward epigenetic and gene regulation models of specific language impairment: Looking for links among growth, genes, and impairments. Journal of Neurodevelopmental Disorders, 4(1), 27. doi:10.1186/1866-1955-4-27Google Scholar

Rietveld, C. A., Medland, S. E., Derringer, J., Yang, J., Esko, T., Martin, N. W., … Koellinger, P. D. (2013). GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. Science, 340(6139), 1467–1471. doi:10.1126/science.1235488Google Scholar

Ripke, S., Neale, B. M., Corvin, A., Walters, J. T. R., Farh, K.-H., Holmans, P. A., … O’Donovan, M. C. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427.Google Scholar

Rocca, M. S., Pecile, V., Cleva, L., Speltra, E., Selice, R., Di Mambro, A., … Ferlin, A. (2016). The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype. Andrology, 4(2), 328–334. doi:10.1111/andr.12146Google Scholar

Sanders, S. J., He, X., Willsey, A. J., Ercan-Sencicek, A. G., Samocha, K. E., Cicek, A. E., … State, M. A. (2015). Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron, 87(6), 1215–1233. doi:10.1016/j.neuron.2015.09.016Google Scholar

Scerri, T. S., Morris, A. P., Buckingham, L. L., Newbury, D. F., Miller, L. L., Monaco, A. P., … Paracchini, S. (2011). DCDC2, KIAA0319 and CMIP are associated with reading-related traits. Biological Psychiatry, 70(3), 237–245. doi:10.1016/j.biopsych.2011.02.005Google Scholar

Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427. doi: 10.1038/nature13595Google Scholar

Sciberras, E., Mueller, K. L., Efron, D., Bisset, M., Anderson, V., Schilpzand, E. J., … Nicholson, J. M. (2014). Language problems in children with ADHD: A community-based study. Pediatrics, 5, 793–800. doi:10.1542/peds.2013-3355Google Scholar

Shriberg, L. D., Tomblin, J. B., & McSweeny, J. L. (1999). Prevalence of speech delay in 6-year-old children and comorbidity with language impairment. Journal of Speech, Language, and Hearing Research, 42(6), 1461–1481. doi:10.1044/jslhr.4206.1461Google Scholar

Simpson, N. H., Ceroni, F., Reader, R. H., Covill, L. E., Knight, J. C., SLI Consortium, … Newbury, D. F. (2015). Genome-wide analysis identifies a role for common copy number variants in specific language impairment. European Journal of Human Genetics, 23(10), 1370–1377. doi:10.1038/ejhg.2014.296Google Scholar

SLI Consortium. (2002). A genomewide scan identifies two novel loci involved in specific language impairment. American Journal of Human Genetics, 70(2), 384–398. doi:10.1086/338649Google Scholar

Smith, S. D. (2011). Approach to epigenetic analysis in language disorders. Journal of Neurodevelopmental Disorders, 3(4), 356–364. doi:10.1007/s11689-011-9099-yGoogle Scholar

Snijders Blok, L., Rousseau, J., Twist, J., Ehresmann, S., Takaku, M., Venselaar, H., … Campeau, P. M. (2018). CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language. Nature Communications, 9(1), 4619. doi:10.1038/s41467-018-06014-6Google Scholar

Soblet, J., Dimov, I., Graf von Kalckreuth, C., Cano-Chervel, J., Baijot, S., Pelc, K., … Deconinck, N. (2018). BCL11a frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems. American Journal of Medical Genetics Part A, 176(1), 201–208. doi:10.1002/ajmg.a.38479Google Scholar

Sollis, E., Graham, S. A., Vino, A., Froehlich, H., Vreeburg, M., Dimitropoulou, D., … Fisher, S. E. (2015). Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder. Human Molecular Genetics, 25(3), 546–557. doi:10.1093/hmg/ddv495Google Scholar

Spinath, F. M., Price, T. S., Dale, P. S., & Plomin, R. (2004). The genetic and environmental origins of language disability and ability. Child Development, 75(2), 445–454. doi:10.1111/j.1467-8624.2004.00685.xGoogle Scholar

Srivastava, S., Cohen, J. S., Vernon, H., Baranano, K., McClellan, R., Jamal, L., … Fatemi, A. (2014). Clinical whole exome sequencing in child neurology practice. Annals of Neurology, 76(4), 473–483. doi:10.1002/ana.24251Google Scholar

St Clair, M. C., Pickles, A., Durkin, K., & Conti-Ramsden, G. (2011). A longitudinal study of behavioral, emotional and social difficulties in individuals with a history of specific language impairment (SLI). Journal of Communication Disorders, 44(2), 186–199. doi:10.1016/j.jcomdis.2010.09.004Google Scholar

St John, M., Ponchard, C., van Reyk, O., Mei, C., Pigdon, L., Amor, D. J., & Morgan, A. T. (2019). Speech and language in children with Klinefelter syndrome. Journal of Communication Disorders, 78, 84–96. doi:10.1016/j.jcomdis.2019.02.003Google Scholar

St Pourcain, B., Cents, R. A. M., Whitehouse, A. J. O., Haworth, C. M. A., Davis, O. S. P., O’Reilly, P. F., … Smith, G. D. (2014). Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nature Communications, 5(5), 4831. doi:10.1038/ncomms5831Google Scholar

Stromswold, K. (1998). Genetics of spoken language disorders. Human Biology, 70(2), 297–324. www.jstor.org/stable/41465640 Google Scholar

The 1000 Genomes Project Consortium. (2015). A global reference for human genetic variation. Nature, 526(7571), 68–74. doi:10.1038/nature15393Google Scholar

Thevenon, J., Callier, P., Andrieux, J., Delobel, B., David, A., Sukno, S., … Faivre, L. (2013). 12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech. European Journal of Human Genetics, 21(1), 82–88. doi:10.1038/ejhg.2012.116Google Scholar

Tomblin, J. B., O’Brien, M., Shriberg, L. D., Williams, C., Murray, J., Patil, S., … Ballard, K. (2009). Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2. Journal of Speech Language and Hearing Research, 52(5), 1157–1174. doi:10.1044/1092-4388(2009/07-0162)Google Scholar

Tomblin, J. B., Records, N. L., Buckwalter, P., Zhang, X., Smith, E., & O’Brien, M. (1997). Prevalence of specific language impairment in kindergarten children. Journal of Speech, Language, and Hearing Research, 40(6), 1245–1260. doi:10.1044/jslhr.4006.1245Google Scholar

Turner, S. J., Hildebrand, M. S., Block, S., Damiano, J., Fahey, M., Reilly, S., … Morgan, A. T. (2013). Small intragenic deletion in foxp2 associated with childhood apraxia of speech and dysarthria. American Journal of Medical Genetics Part A, 161a(9), 2321–2326. doi:10.1002/ajmg.a.36055Google Scholar

Van der Aa, N., Vandeweyer, G., Reyniers, E., Kenis, S., Dom, L., Mortier, G., … Kooy, R. F. (2012). Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2. Autism Research, 5(4), 277–281. doi:10.1002/aur.1240Google Scholar

Van Ijzendoorn, M. H., Belsky, J., & Bakermans-Kranenburg, M. J. (2012). Serotonin transporter genotype 5HTTLPR as a marker of differential susceptibility? A meta-analysis of child and adolescent gene-by-environment studies. Translational Psychiatry, 2, e147. doi:10.1038/tp.2012.73Google Scholar

Veltman, J. A., & Brunner, H. G. (2010). Understanding variable expressivity in microdeletion syndromes. Nature Genetics, 42(3), 192–193. doi:10.1038/ng0310-192Google Scholar

Vernes, S. C., Newbury, D. F., Abrahams, B. S., Winchester, L., Nicod, J., Groszer, M., … Fisher, S. E. (2008). A functional genetic link between distinct developmental language disorders. New England Journal of Medicine, 359(22), 2337–2345. doi:10.1056/NEJMoa0802828Google Scholar

Villanueva, P., Newbury, D. F., Jara, L., De Barbieri, Z., Mirza, G., Palomino, H. M., … Palomino, H. (2011). Genome-wide analysis of genetic susceptibility to language impairment in an isolated Chilean population. European Journal of Human Genetics, 19, 687–695. doi:10.1038/ejhg.2010.251Google Scholar

Virgin, H. W., & Todd, J. A. (2011). Metagenomics and personalized medicine. Cell, 147(1), 44–56. doi:10.1016/j.cell.2011.09.009CrossRef Google Scholar PubMed

Wainschtein, P., Jain, D., Zheng, Z., TOPMed Anthropometry Working Group, Cupples, L. A., Shadyab, A. H., … Visscher, P. M. (2019). Recovery of trait heritability from whole genome sequence data. bioRxiv, 588020. doi:10.1101/588020Google Scholar

Wake, M., Poulakis, Z., Hughes, E. K., Carey-Sargeant, C., & Rickards, F. W. (2005). Hearing impairment: A population study of age at diagnosis, severity, and language outcomes at 7–8 years. Archives of Disease in Childhood, 90(3), 238–244. doi:10.1136/adc.2003.039354Google Scholar

White, S. M., Morgan, A. T., Da Costa, A., Lacombe, D., Knight, S. J. L., Houlston, R., … Hurst, J. A. (2010). The phenotype of Floating-Harbor syndrome in 10 patients. American Journal of Medical Genetics, Part A, 152A(4), 821–829. doi:10.1002/ajmg.a.33294CrossRef Google Scholar PubMed

Whitehouse, A. J., Bishop, D. V., Ang, Q. W., Pennell, C. E., & Fisher, S. E. (2011). CNTNAP2 variants affect early language development in the general population. Genes, Brain and Behavior, 10(4), 451–456. doi:10.1111/j.1601-183X.2011.00684.xGoogle Scholar

World Health Organisation. (2010). ICD-10: International statistical classification of diseases and related health problems (10th rev. ed.). Geneva: World Health Organization. https://icd.who.int/browse10/2010/en#/F80-F89 Google Scholar

Zeesman, S., Nowaczyk, M. J., Teshima, I., Roberts, W., Cardy, J. O., Brian, J., … Scherer, S. W. (2006). Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2. American Journal of Medical Genetics Part A, 140(5), 509–514. doi:10.1002/ajmg.a.31110Google Scholar

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the HTML of this chapter is currently unknown and may be updated in the future.

Book contents

3 - Genetic Studies of Language Disorders

Summary