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Communication impairments are commonly reported, yet specific speech and language diagnoses have not been delineated, preventing prognostic counseling and targeted therapies. Here, we characterized speech and language in 38 female individuals, aged 1.69\u201324.34\u2009years, with pathogenic and likely pathogenic <jats:italic>DDX3X<\/jats:italic> variants (missense, <jats:italic>n<\/jats:italic>\u2009=\u200913; nonsense, <jats:italic>n<\/jats:italic>\u2009=\u200912; frameshift, <jats:italic>n<\/jats:italic>\u2009=\u20097; splice site, <jats:italic>n<\/jats:italic>\u2009=\u20093; synonymous, <jats:italic>n<\/jats:italic>\u2009=\u20092; deletion, <jats:italic>n<\/jats:italic>\u2009=\u20091). Standardized speech, language, motor, social, and adaptive behavior assessments were administered. All participants had gross motor deficits in infancy (34\/34), and fine motor deficits were common throughout childhood (94%; 32\/34). Intellectual disability was reported in 86% (24\/28) of participants over 4\u2009years of age. Expressive, receptive, and social communication skills were, on average, severely impaired. However, receptive language was significantly stronger than expressive language ability. Over half of the assessed participants were minimally verbal (66%; 22\/33; range\u2009=\u20092\u2009years 2\u2009months\u201324\u2009years 4\u2009months; mean\u2009=\u20098\u2009years; <jats:italic>SD<\/jats:italic>\u2009=\u20096\u2009years) and augmented speech with sign language, gestures, or digital devices. A quarter of the cohort had childhood apraxia of speech (25%; 9\/36). Despite speech and language impairments, social motivation was a relevant strength. Many participants used augmentative and alternative communication (AAC), underscoring the need for early, tailored, and comprehensive AAC intervention.<\/jats:p>","DOI":"10.1002\/ajmg.b.32971","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T12:18:44Z","timestamp":1709209124000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Speech and language in <i>DDX3X<\/i>\u2010neurodevelopmental disorder: A call for early augmentative and alternative communication intervention"],"prefix":"10.1002","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5412-738X","authenticated-orcid":false,"given":"Elana J.","family":"Forbes","sequence":"first","affiliation":[{"name":"Speech &amp; Language Murdoch Children's Research Institute  Melbourne Victoria Australia"},{"name":"School of Psychological Sciences Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2822-6522","authenticated-orcid":false,"given":"Lottie D.","family":"Morison","sequence":"additional","affiliation":[{"name":"Speech &amp; 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Language Murdoch Children's Research Institute  Melbourne Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7405","authenticated-orcid":false,"given":"Angela T.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Speech &amp; Language Murdoch Children's Research Institute  Melbourne Victoria Australia"},{"name":"Department of Audiology and Speech Pathology University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000289"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1044\/aac16.1.10"},{"key":"e_1_2_10_5_1","volume-title":"The children's communication checklist, in CCC\u20102","author":"Bishop D. 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