{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T05:59:31Z","timestamp":1767765571695,"version":"3.48.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"NIH NCATS","doi-asserted-by":"crossref","award":["1U01TR002764-01A"],"award-info":[{"award-number":["1U01TR002764-01A"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"NIH National Human Genome Research Institute","doi-asserted-by":"crossref","award":["U24HG006834"],"award-info":[{"award-number":["U24HG006834"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Speech and language delay (SLD) is one of the most prevalent developmental conditions in childhood, with post-pandemic data indicating a notable increase in identified cases. Within this group, expressive language disorder (ELD) frequently appears alongside neurodevelopmental disorders such as autism spectrum disorder (ASD), epilepsy, and intellectual disability. Although awareness of ELD has grown, the role of genetic testing in its evaluation remains unclear, as such testing is not routinely pursued for isolated expressive language concerns. This gap highlights the need to better define the diagnostic value of genetic analysis and to examine the interval between an ELD diagnosis and the return of genetic testing results. Methods: This study investigated genetic contributions to ELD using the National Brain Gene Registry (BGR), a multisite database of rare neurodevelopmental disorders. Participants with ICD-10 code F80.1 were identified through electronic health records; demographic data, comorbidities, genetic variants, inheritance patterns, age at diagnosis, and timing of interventions were analyzed. Results: Of 687 BGR participants, 32 (4.7%) had documented ELD. The cohort, aged 3\u201319 years, presented with common comorbidities like developmental delays, ASD, epilepsy, and hypotonia. Across 42 genes, 49 unique variants were identified: 26 pathogenic or likely pathogenic, 22 variants of uncertain significance, and one benign variant. Seventeen variants were de novo, and 10 participants carried multiple variants. Most children (80%) received an expressive language diagnosis prior to genetic testing, with reports returned an average of 1.5 years following the diagnosis. Conclusions: Overall, children with ELD commonly carry genetic variants and neurodevelopmental comorbidities, yet genetic testing is typically pursued well after diagnosis and does not currently alter early management. These findings underscore the need for clearer, evidence-based guidelines to define when genetic testing adds diagnostic or prognostic value in the evaluation of ELD.<\/jats:p>","DOI":"10.3390\/genes17010061","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Genetic Testing in Pediatric Expressive Language Delay: Evidence from the National Brain Gene Registry"],"prefix":"10.3390","volume":"17","author":[{"given":"Shivani","family":"Waghmare","sequence":"first","affiliation":[{"name":"Howard University College of Medicine, Washington, DC 20001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-804X","authenticated-orcid":false,"given":"Alexa M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Children\u2019s National Medical Center, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Bouska","sequence":"additional","affiliation":[{"name":"Children\u2019s National Medical Center, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1707-5938","authenticated-orcid":false,"given":"Ana","family":"Moreno Chaza","sequence":"additional","affiliation":[{"name":"Children\u2019s National Medical Center, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Gropman","sequence":"additional","affiliation":[{"name":"Children\u2019s National Medical Center, Washington, DC 20010, USA"},{"name":"St. Jude\u2019s Children\u2019s Research Hospital, Memphis, TN 38105-3678, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","unstructured":"(2025, February 25). Quick Statistics About Voice, Speech, Language|NIDCD, Available online: https:\/\/www.nidcd.nih.gov\/health\/statistics\/quick-statistics-voice-speech-language."},{"key":"ref_2","unstructured":"(2025, February 24). Speech_Pathology_Research_Brief.pdf. Available online: https:\/\/www.komodohealth.com\/perspectives\/louder-than-words-pediatric-speech-disorders-skyrocket-throughout-pandemic\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1542\/pir.2017-0325","article-title":"How young children learn language and speech","volume":"40","author":"Feldman","year":"2019","journal-title":"Pediatr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1044\/1058-0360(2008\/08-0064)","article-title":"Is expressive language disorder an accurate diagnostic category?","volume":"18","author":"Leonard","year":"2009","journal-title":"Am. J. Speech Lang. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sansavini, A., Favilla, M.E., Guasti, M.T., Marini, A., Millepiedi, S., Di Martino, M.V., Vecchi, S., Battajon, N., Bertolo, L., and Capirci, O. (2021). Developmental language disorder: Early predictors, age for the diagnosis, and diagnostic tools. A scoping review. Brain Sci., 11.","DOI":"10.3390\/brainsci11050654"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1080\/15374416.2013.822306","article-title":"Merely misunderstood? Receptive, expressive, and pragmatic language in young children with disruptive behavior disorders","volume":"43","author":"Gremillion","year":"2014","journal-title":"J. Clin. Child. Adolesc. Psychol."},{"key":"ref_7","unstructured":"Morgan, A., Fisher, S.E., Scheffer, I., and Hildebrand, M. (2016). FOXP2-related speech and language disorder. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_8","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2016). GRIN2A-related disorders. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_9","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2017). UNC80 Deficiency. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_10","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2020). MN1 C-terminal truncation syndrome. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1044\/2022_AJSLP-21-00328","article-title":"The language profile of preschool children with 22q11.2 deletion syndrome and the relationship with speech intelligibility","volume":"32","author":"Everaert","year":"2023","journal-title":"Am. J. Speech Lang. Pathol."},{"key":"ref_12","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2012). Zar-Kessler CPitt-Hopkins Syndrome. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ridd.2017.11.010","article-title":"A meta-analysis of the association between vocalizations and expressive language in children with autism spectrum disorder","volume":"72","author":"McDaniel","year":"2018","journal-title":"Res. Dev. Disabil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1038\/s41380-022-01879-y","article-title":"Correction: Genetic aetiologies for childhood speech disorder: Novel pathways co-expressed during brain development","volume":"28","author":"Kaspi","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s11689-024-09530-3","article-title":"The Brain Gene Registry: A data snapshot","volume":"16","author":"Baldridge","year":"2024","journal-title":"J. Neurodev. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Plug, M.B., van Wijngaarden, V., de Wilde, H., van Binsbergen, E., Stegeman, I., van den Boogaard, M.H., and Smit, A.L. (2021). Clinical characteristics and genetic etiology of children with developmental language disorder. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.651995"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1001\/jama.2013.3239","article-title":"New approaches to molecular diagnosis","volume":"309","author":"Korf","year":"2013","journal-title":"JAMA"},{"key":"ref_18","first-page":"55","article-title":"Approach to Developmental Screening and Surveillance in Young Children","volume":"112","author":"Koopman","year":"2025","journal-title":"Am. Fam. Physician."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2025072219","DOI":"10.1542\/peds.2025-072219","article-title":"Genetic Evaluation of the Child with Intellectual Disability or Global Developmental Delay: Clinical Report","volume":"156","author":"Rodan","year":"2025","journal-title":"Pediatrics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/cge.13389","article-title":"Enrichment of rare copy number variation in children with developmental language disorder","volume":"94","author":"Kalnak","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00439-023-02636-z","article-title":"Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder","volume":"143","author":"Yahia","year":"2024","journal-title":"Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/ana.24251","article-title":"Clinical whole exome sequencing inchild neurology practice","volume":"76","author":"Srivastava","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1001\/jama.2023.24647","article-title":"Screening for speech and language delay and disorders in children 5 years or younger: Evidence report and systematic review for the US preventive services task force","volume":"331","author":"Feltner","year":"2024","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"US Preventive Services Task Force, Barry, M.J., Nicholson, W.K., Silverstein, M., Chelmow, D., Coker, T.R., Davis, E.M., Donahue, K.E., Ja\u00e9n, C.R., and Li, L. (2024). Screening for speech and language delay and disorders in children: US prev33entive services task force recommendation statement. JAMA, 331, 329\u2013334.","DOI":"10.1001\/jama.2023.26952"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/jcpp.13858","article-title":"Annual Research Review: Early intervention viewed through the lens of developmental neuroscience","volume":"65","author":"Nelson","year":"2024","journal-title":"J. Child. Psychol. Psychiatry"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T05:27:18Z","timestamp":1767763638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["genes17010061"],"URL":"https:\/\/doi.org\/10.3390\/genes17010061","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2026,1,5]]}}}