{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T08:12:52Z","timestamp":1771056772090,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,4]]},"group-title":"Neurology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rationale<\/jats:title>\n                  <jats:p>Neurodevelopmental disorders (NDDs) are characterised by significant challenges in communication, social interaction, and adaptive function, often impacting quality of life. Previous studies support genetic influences on the communication abilities of individuals with NDD, but were either limited to single genetic conditions or to small cohorts with a limited selection of communication measures.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We analysed caregiver-reported communication abilities in 79,518 individuals with NDD from the Simons Searchlight and SPARK registries: 4,439 with a CNV-based or monogenic NDD and 75,079 with autism spectrum disorder (ASD) without a known genetic cause (idiopathic ASD) as controls. For analysis, we a priori selected 10 communication-related measures based on their availability in the study cohorts, coverage of distinct communication aspects, and their frequent use in neurodevelopmental phenotyping, yielding 177,328 data points across all study cohorts. The individuals in the Searchlight registry were divided into a\n                    <jats:italic>Discovery<\/jats:italic>\n                    cohort (the 15 most prevalent genetic NDD conditions) and a\n                    <jats:italic>Confirmation<\/jats:italic>\n                    cohort (all other genetic NDD conditions). A second\n                    <jats:italic>Confirmation<\/jats:italic>\n                    cohort was generated using all individuals with genetic ASD forms from the SPARK registry. We then tested each of the three case cohorts and each genetic condition represented in the\n                    <jats:italic>Discovery<\/jats:italic>\n                    cohort against the ASD control cohort. Developmental trajectories were assessed through testing of participants grouped by age at evaluation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Measure-level analyses demonstrated significant associations between genetic status and communication abilities, differences in communication abilities between classes of genetic variants (monogenic vs. CNV-based NDDs), and variability between specific genetic NDD conditions. CNV-based NDDs showed milder communication impairment, outperforming idiopathic ASD controls in 9\/10 communication measures, whereas monogenic NDD conditions had more pervasive impairments, especially in verbal communication. Although impaired in verbal communication, five monogenic NDD conditions showed at least suggestive strengths in nonverbal and social communication relative to idiopathic ASD controls (\n                    <jats:italic>CSNK2A1<\/jats:italic>\n                    ,\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    ,\n                    <jats:italic>SETBP1<\/jats:italic>\n                    ,\n                    <jats:italic>MED13L<\/jats:italic>\n                    , and\n                    <jats:italic>PPP2R5D<\/jats:italic>\n                    ), specifically in using gestures. Developmental trajectory analyses revealed\n                    <jats:italic>STXBP1<\/jats:italic>\n                    as the gene group at highest risk of developmental stagnation in communication abilities.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings underscore the potential of precision speech-language pathology (SLP) approaches tailored to the specific verbal and nonverbal communication strengths and weaknesses of genetic groups. We also provide evidence for measurable improvements and declines in communication abilities with age at the group level, highlighting the need for developmentally informed care. By integrating genetic insights into clinical practice, precision SLP approaches may enhance communication outcomes and developmental progress and improve quality of life for individuals with genetic NDDs.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.03.26345484","type":"posted-content","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T01:30:29Z","timestamp":1770255029000},"source":"Crossref","is-referenced-by-count":0,"title":["Genotype-specific communication profiles in 79,518 individuals with neurodevelopmental disorders"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-2927","authenticated-orcid":false,"given":"Cristiane","family":"Hsu","sequence":"first","affiliation":[{"name":"TIRR Memorial Hermann Outpatient Rehabilitation, Memorial Hermann Health System, Houston, TX 77030, US"},{"name":"Department of Neurology, McGovern Medical School, UTHealth Houston, Houston, TX 77030, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-3112","authenticated-orcid":false,"given":"Alina","family":"Ivaniuk","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic Florida, Jacksonville, FL 32224, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Jimenez-Gomez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, TX 77030, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2591-432X","authenticated-orcid":false,"given":"Tobias","family":"Br\u00fcnger","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School, UTHealth Houston, Houston, TX 77030, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1596-5599","authenticated-orcid":false,"given":"Christian M.","family":"Bo\u00dfelmann","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, DE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-846X","authenticated-orcid":false,"given":"M. Scott","family":"Perry","sequence":"additional","affiliation":[{"name":"Jane and John Justin Institute for Mind Health, Cook Children\u2019s Medical Center, Fort Worth, TX 76104, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Phan","sequence":"additional","affiliation":[{"name":"TIRR Memorial Hermann Outpatient Rehabilitation, Memorial Hermann Health System, Houston, TX 77030, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5845-9610","authenticated-orcid":false,"given":"Ana","family":"Arenivas","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, US"},{"name":"Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7448-9986","authenticated-orcid":false,"given":"Haley O.","family":"Oyler","sequence":"additional","affiliation":[{"name":"SETBP1 Society, Austin, TX, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha N.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Kennedy Krieger Institute, Johns Hopkins School of Medicine, Center for Neuropsychological and Psychological Assessment\/Psychiatry and Behavioral Sciences, Baltimore, MD 21205, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-3301","authenticated-orcid":false,"given":"Costin","family":"Leu","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School, UTHealth Houston, Houston, TX 77030, US"},{"name":"Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School, UTHealth Houston, Houston, TX 77030, US"},{"name":"Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, US"},{"name":"Center of Neurogenetics, UTHealth Houston, Houston, TX 77030, US"},{"name":"Stanley Center for Psychiatric Research, Broad Institute of Harvard and M.I.T, Cambridge, MA 02142, US"},{"name":"Cook Children\u2019s Medical Center, Fort Worth, TX 76104, US"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026021323401285000_2026.02.03.26345484v2.1","unstructured":"American Psychiatric Association. 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