{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:07:41Z","timestamp":1790431661276,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pathogenic variants in the non\u2010coding spliceosomal gene RNU4\u20102 underlie ReNU syndrome, one of the most prevalent monogenic causes of neurodevelopmental disorders, accounting for ~0.4% of cases. Despite increasing recognition, little is known about the longitudinal behavioral and neuropsychiatric phenotype of affected individuals. We report two patients with RNU4\u20102 variants, providing a comprehensive description of their developmental trajectories from infancy to adolescence. Both exhibited global developmental delay, impaired adaptive functioning, and significant language deficits. Distinctive features included persistent attention deficits and Autistic Spectrum Disorder, which emerged as hallmarks of the Syndrome. Case\u2010specific differences were notable: one patient developed self\u2010injurious behavior and social anxiety during adolescence, while the other presented with epilepsy and structural brain anomalies. Neuroimaging revealed convergent features, including white matter reduction, corpus callosum thinning, and ventricular dysmorphisms. Our findings highlight the importance of early, individualized interventions, with particular emphasis on augmentative and alternative communication strategies and cognitive\u2010behavioral approaches to mitigate communicative frustration, behavioral dysregulation, and social anxiety. This study provides the first longitudinal neuropsychiatric characterization of RNU4\u20102\u2010related disorder, delineating clinical hallmarks, and therapeutic windows. A better understanding of developmental trajectories in this condition is essential to optimize patient management and improve long\u2010term outcomes.<\/jats:p>","DOI":"10.1002\/ajmgb.70004","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:15:01Z","timestamp":1770959701000},"page":"205-211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Longitudinal Behavior Phenotype Hallmarks in RNU4\u20102 Syndrome: Implications for Clinical Management"],"prefix":"10.1002","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-4634","authenticated-orcid":false,"given":"Paola Francesca","family":"Ajmone","sequence":"first","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Service (UONPIA), Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Rigamonti","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Service (UONPIA), Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Brasca","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Service (UONPIA), Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Milani","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Ranci","family":"Ortigosa","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Service (UONPIA), Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-212X","authenticated-orcid":false,"given":"Maria","family":"Iascone","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, ASST Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Goisis","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, ASST Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalaura","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli, Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonella","family":"Costantino","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Service (UONPIA), Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Manual for the ASEBA School\u2010Age Forms and Profiles","author":"Achenbach T. 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