Imaging Findings in a Child with RNU4-2 (ReNU) Syndrome: A Paediatric Neuroradiology Case Report

Imaging Findings in a Child with RNU4-2 (ReNU) Syndrome: A Paediatric Neuroradiology Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Imaging Findings in a Child with RNU4-2 (ReNU) Syndrome: A Paediatric Neuroradiology Case Report Conor Waters, Shauna Quinn, Olivia Carney, Aedín Ryan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8737785/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background RNU4-2–related neurodevelopmental disorder (ReNU syndrome) is an emerging genetic condition associated with global developmental delay and seizures. Neuroimaging findings are increasingly recognized but remain incompletely characterized. Case Presentation: We describe a 3½-year-old child presenting with seizure and a history developmental delay whose MRI demonstrated polymicrogyria, ventriculomegaly and dysgenesis of the corpus callosum. These findings, in conjunction with clinical and genetic assessment, supported the diagnosis of RNU4-2 syndrome. Conclusion This case highlights characteristic and potentially distinctive neuroimaging features of RNU4-2 syndrome, expanding the radiologic phenotype and potentially aiding early recognition in paediatric patients with seizures and developmental delay. RNU4-2 syndrome paediatric neuroradiology neurodevelopmental disorders magnetic resonance imaging Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction RNU4-2 syndrome is an emerging neurodevelopmental disorder caused by variations in the RNU4-2 gene, associated with global developmental delay, dysmorphic facial features and hypotonia [ 1 ]. Given the recent discovery of this disorder, first published in May 2024, the imaging features are still evolving [ 2 ]. RNU4-2 syndrome is thought to account for 0.4% of neurodevelopmental disorders [ 1 ]. Paediatric radiologists may encounter these cases in day to day practise and identification of the associated imaging findings can provide critical diagnostic clues. Reported imaging findings to date include corpus callosum hypoplasia, ventriculomegaly and reduced white matter volume [ 1 ]. This case report contains many of the previously described imaging features, with the addition of multiple findings not previously described in RNU4-2 syndrome to the best of our knowledge. Case Report Clinical Presentation We report the case of a 3½-year-old boy who presented with a complex febrile seizure. He is the first child of healthy, non-consanguineous parents. Pregnancy was concerning for intrauterine growth restriction and an increased nuchal translucency on antenatal ultrasound. Subsequent non-invasive prenatal testing (Harmony) was low-risk, and interval imaging demonstrated resolution of these findings. He was delivered at term via induced vaginal delivery for reduced foetal movements, with a birth weight of 2.8 kg, and had an uncomplicated postnatal course. During infancy, he developed significant torticollis at 4 months of age, which resolved following physiotherapy. At 9 months, he was admitted with viral gastroenteritis, during which developmental delay and hypermobility were first noted, prompting referral to the local Neurodisability services. Additional comorbidities included: left strabismus and hyperopia requiring ophthalmologic follow-up, as well as an atrial septal defect and patent foramen ovale identified on systemic evaluation and echocardiography. He exhibited global developmental delay, most prominent in the gross motor and expressive language domains. He achieved independent sitting at 10 months and walked at 30 months. He remains non-verbal but communicates using hand signals and Lámh signing, with preservation of receptive language. No developmental regression has been observed. The patient presented with two febrile seizures within a 30-minute interval, each lasting more than five minutes and characterized by eye deviation, oral frothing, and distal limb twitching. Neurological examination was unremarkable. Laboratory investigations and electroencephalography (EEG) were within normal limits. Imaging Findings MRI Protocol Brain MRI was performed on a 1.5 Tesla system. Sequences included sagittal T1, 3D T1, axial and coronal T2, axial FLAIR, 3D FLAIR, diffusion-weighted imaging and susceptibility-weighted imaging. Key Findings Microcephaly (figure 1) Corpus callosum hypoplasia (figure 1) Predominant hypoplasia of the body and splenium of the corpus callosum. Reduced periventricular white matter volume and ventriculomegaly (figure 2) Reduced volume of white matter predominantly surrounding the occipital horns of the lateral ventricles with associated enlargement of the lateral ventricles. Polymicrogyria (figure 3) Excessive abnormal small gyri in the frontal lobes with an irregular cortical surface and ill-defined grey-white matter junction. Enlargement of the interpeduncular cistern (figure 4) Incomplete hippocampal inversion (figure 5) Genetic Testing Trio whole-exome sequencing subsequently identified a heterozygous, de novo pathogenic variant in RNU4-2 , consisting of a single-nucleotide thymine insertion at position n.64_65 (HGVS: RNU4-2 n.64_65insT). This variant occurs within the transcribed small nuclear RNA sequence and is associated with a recently described syndromic neurodevelopmental disorder, correlating with the patient’s clinical phenotype and radiological findings. Discussion Many radiological features of RNU4-2 syndrome have been described to date. Common features reported in case reports include corpus callosum hypoplasia and ventriculomegaly [ 3 – 5 ]. Other reported imaging findings include microcephaly and reduced volume of periventricular white matter [ 1 ]. This case contains all of these findings, further emphasising their commonality in RNU4-2 syndrome. In addition to these features, this case also features polymicrogyria, enlargement of the interpeduncular cistern and incomplete hippocampal inversion. These are new findings in RNU4-2 syndrome to the best of our knowledge. This case expands the neuroimaging phenotype of RNU4-2 syndrome, providing a detailed MRI assessment of a condition with limited imaging literature. Given that RNU4-2 syndrome is suspected to be a common neurogenetic disorder, it is important we add to the knowledge of its radiological findings. Further consolidating previously described imaging findings while describing new features adds to the education and awareness of this syndrome amongst radiologists and potentially aids in the identification of RNU4-2 syndrome in future cases. It is always important to interpret imaging findings as a collective with the aim of piecing together findings to a diagnosis or set of differential diagnoses. Identifying findings is the first step but this case highlights the importance of connecting individual imaging findings. Radiologists have a role in suggesting the possibility of neurogenetic disorders in cases such as this, potentially prompting genetic testing. Conclusion RNU4-2 syndrome is a newly characterized condition in which neuroimaging plays a central diagnostic role. This case demonstrates distinctive imaging features of RNU4-2 syndrome which adds to the limited literature and may aid Radiologists making this diagnosis in children presenting with developmental delay and seizures. Declarations The authors declare that they have no financial or non-financial interests that are directly or indirectly related to the work submitted for publication. Written informed consent for publication of clinical details and images was obtained from the patient’s legal guardians. Author Contribution C.W. wrote the following sections of the manuscript: Abstract, introduction, imaging findings section, discussion and conclusion. S.Q. and A.E. wrote the clinical presentation and genetic testing sections of the manuscript.O.C. and C.W. both interpreted the images and came to consensus agreement on the findings.All authors reviewed the manuscript. References Barbour K et al (2024) The face and features of RNU4-2: A new, common, recognizable, yet hidden neurodevelopmental disorder. Pediatr Neurol 161:188–193. 10.1016/j.pediatrneurol.2024.09.015 Greene D et al (2024) Mutations in the U4 snrna gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders. Nat Med 30(8):2165–2169. 10.1038/s41591-024-03085-5 Valenzuela I et al (2024) Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome. Genet Sci 26(12):101288. 10.1016/j.gim.2024.101288 Jackson A et al (2025) Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as Neurodevelopmental Disorder Genes. Nat Genet 57(6):1362–1366. 10.1038/s41588-025-02209-y De Jonghe J et al (2025) Saturation genome editing of RNU4–2 reveals distinct dominant and recessive neurodevelopmental disorders [Preprint]. 10.1101/2025.04.08.25325442 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8737785","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":593394032,"identity":"b1f2c0e3-cb9e-462d-9236-616e389ab6c5","order_by":0,"name":"Conor Waters","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYJADxgcJFUCKmbmBKOUSILUGD86AKEbitbBJPmwD24ZfC39778HHlW12dfzSx59JJM6rjeZvB2r5UbENt+lnziUbnm1LlpDsyzG2SNx2PHfGYcYGxp4zt3FqMZDIMZNs3MYsYXCGh/FG4rZjuQ1ALcyMbQS11EvYn2F/IJE451jufCK1HJYw4GEwkkhsqMndQEiLxJkzxoaN/45LzjjDY2yQcOxA7kagloP4/MLf3mP4sOFMNT9/D/vDhz9q6nLnnT988MGPCtxa0MFhMHmAaPVAUEeK4lEwCkbBKBghAAC3VVly7GfcaAAAAABJRU5ErkJggg==","orcid":"","institution":"University Hospital Galway","correspondingAuthor":true,"prefix":"","firstName":"Conor","middleName":"","lastName":"Waters","suffix":""},{"id":593394034,"identity":"2390d5e9-dbe8-4488-891b-2305ed3a49f7","order_by":1,"name":"Shauna Quinn","email":"","orcid":"","institution":"University Hospital Galway","correspondingAuthor":false,"prefix":"","firstName":"Shauna","middleName":"","lastName":"Quinn","suffix":""},{"id":593394036,"identity":"b02f739f-89a0-4b96-a476-ac26782e7dce","order_by":2,"name":"Olivia Carney","email":"","orcid":"","institution":"University Hospital Galway","correspondingAuthor":false,"prefix":"","firstName":"Olivia","middleName":"","lastName":"Carney","suffix":""},{"id":593394037,"identity":"5bbed6dc-0b7f-4966-b970-f338cba1de0c","order_by":3,"name":"Aedín Ryan","email":"","orcid":"","institution":"University Hospital Galway","correspondingAuthor":false,"prefix":"","firstName":"Aedín","middleName":"","lastName":"Ryan","suffix":""}],"badges":[],"createdAt":"2026-01-30 06:23:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8737785/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8737785/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103176876,"identity":"9c9e870c-2d34-4a1a-8211-77eb34bf0b5d","added_by":"auto","created_at":"2026-02-22 16:39:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76163,"visible":true,"origin":"","legend":"\u003cp\u003eSagittal T1-weighted MRI showing microcephaly and corpus callosum hypoplasia (black arrow).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8737785/v1/fe4df408befc2d86ddcb52eb.jpg"},{"id":103176878,"identity":"5e5878cc-8897-447d-baf4-d9674391b034","added_by":"auto","created_at":"2026-02-22 16:39:20","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":151049,"visible":true,"origin":"","legend":"\u003cp\u003eAxial T2-weighted MRI demonstrating ventriculomegaly and reduced volume of periventricular white matter, particularly evident surrounding the occipital horns.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8737785/v1/b6b5b52752817e32fe6c59d9.jpg"},{"id":103176885,"identity":"a0450d82-9982-4c02-bfed-f4a94ddd0920","added_by":"auto","created_at":"2026-02-22 16:39:24","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":157372,"visible":true,"origin":"","legend":"\u003cp\u003eThree slices of an axial T2-weighted MRI showing polymicrogyria in both frontal lobes (white arrows). This images also demonstrate ventriculomegaly and reduced white matter surrounding the occipital horns of the lateral ventricles.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8737785/v1/bbe0f5721afb90d69a2b5c4d.jpg"},{"id":103176850,"identity":"e74a953f-c05c-483d-9993-ad20bc76a3e3","added_by":"auto","created_at":"2026-02-22 16:39:13","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":81579,"visible":true,"origin":"","legend":"\u003cp\u003eAxial T2-weighted MRI demonstrating enlargement of the interpeduncular cistern and reduced white matter surrounding the occipital horns of the lateral ventricles.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8737785/v1/936a4c9e4662f7b563f150d1.jpg"},{"id":103176857,"identity":"8aee5d28-44ab-4873-9a21-725274b9b53b","added_by":"auto","created_at":"2026-02-22 16:39:16","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":69205,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal T2-weighted MRI demonstrating incomplete inversion of the left hippocampus (white arrow).\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8737785/v1/e15bdfaf13531ef7de2589bf.jpg"},{"id":105563091,"identity":"d22fe7a6-6a5d-440b-8f5c-c71bee35fd54","added_by":"auto","created_at":"2026-03-27 12:45:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":811661,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8737785/v1/9fd1a247-c12b-4be2-9886-24c57dea30d0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Imaging Findings in a Child with RNU4-2 (ReNU) Syndrome: A Paediatric Neuroradiology Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRNU4-2 syndrome is an emerging neurodevelopmental disorder caused by variations in the RNU4-2 gene, associated with global developmental delay, dysmorphic facial features and hypotonia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Given the recent discovery of this disorder, first published in May 2024, the imaging features are still evolving [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. RNU4-2 syndrome is thought to account for 0.4% of neurodevelopmental disorders [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Paediatric radiologists may encounter these cases in day to day practise and identification of the associated imaging findings can provide critical diagnostic clues.\u003c/p\u003e \u003cp\u003eReported imaging findings to date include corpus callosum hypoplasia, ventriculomegaly and reduced white matter volume [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This case report contains many of the previously described imaging features, with the addition of multiple findings not previously described in RNU4-2 syndrome to the best of our knowledge.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eClinical Presentation\u003c/p\u003e \u003cp\u003eWe report the case of a 3\u0026frac12;-year-old boy who presented with a complex febrile seizure.\u003c/p\u003e \u003cp\u003eHe is the first child of healthy, non-consanguineous parents. Pregnancy was concerning for intrauterine growth restriction and an increased nuchal translucency on antenatal ultrasound. Subsequent non-invasive prenatal testing (Harmony) was low-risk, and interval imaging demonstrated resolution of these findings. He was delivered at term via induced vaginal delivery for reduced foetal movements, with a birth weight of 2.8 kg, and had an uncomplicated postnatal course.\u003c/p\u003e \u003cp\u003eDuring infancy, he developed significant torticollis at 4 months of age, which resolved following physiotherapy. At 9 months, he was admitted with viral gastroenteritis, during which developmental delay and hypermobility were first noted, prompting referral to the local Neurodisability services. Additional comorbidities included: left strabismus and hyperopia requiring ophthalmologic follow-up, as well as an atrial septal defect and patent foramen ovale identified on systemic evaluation and echocardiography.\u003c/p\u003e \u003cp\u003eHe exhibited global developmental delay, most prominent in the gross motor and expressive language domains. He achieved independent sitting at 10 months and walked at 30 months. He remains non-verbal but communicates using hand signals and L\u0026aacute;mh signing, with preservation of receptive language. No developmental regression has been observed.\u003c/p\u003e \u003cp\u003eThe patient presented with two febrile seizures within a 30-minute interval, each lasting more than five minutes and characterized by eye deviation, oral frothing, and distal limb twitching. Neurological examination was unremarkable. Laboratory investigations and electroencephalography (EEG) were within normal limits.\u003c/p\u003e \u003cp\u003eImaging Findings\u003c/p\u003e \u003cp\u003eMRI Protocol\u003c/p\u003e \u003cp\u003eBrain MRI was performed on a 1.5 Tesla system. Sequences included sagittal T1, 3D T1, axial and coronal T2, axial FLAIR, 3D FLAIR, diffusion-weighted imaging and susceptibility-weighted imaging.\u003c/p\u003e \u003cp\u003eKey Findings\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eMicrocephaly (figure 1)\u003c/li\u003e\n \u003cli\u003eCorpus callosum hypoplasia (figure 1)\u003cul\u003e\n \u003cli\u003ePredominant hypoplasia of the body and splenium of the corpus callosum.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eReduced periventricular white matter volume and ventriculomegaly (figure 2)\u003cul\u003e\n \u003cli\u003eReduced volume of white matter predominantly surrounding the occipital horns of the lateral ventricles with associated enlargement of the lateral ventricles.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003ePolymicrogyria (figure 3)\u003cul\u003e\n \u003cli\u003eExcessive abnormal small gyri in the frontal lobes with an irregular cortical surface and ill-defined grey-white matter junction.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eEnlargement of the interpeduncular cistern (figure 4)\u003c/li\u003e\n \u003cli\u003eIncomplete hippocampal inversion (figure 5)\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e \u003cp\u003eGenetic Testing\u003c/p\u003e \u003cp\u003eTrio whole-exome sequencing subsequently identified a heterozygous, de novo pathogenic variant in \u003cb\u003eRNU4-2\u003c/b\u003e, consisting of a single-nucleotide thymine insertion at position n.64_65 (HGVS: \u003cem\u003eRNU4-2\u003c/em\u003e n.64_65insT). This variant occurs within the transcribed small nuclear RNA sequence and is associated with a recently described syndromic neurodevelopmental disorder, correlating with the patient\u0026rsquo;s clinical phenotype and radiological findings.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMany radiological features of RNU4-2 syndrome have been described to date. Common features reported in case reports include corpus callosum hypoplasia and ventriculomegaly [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Other reported imaging findings include microcephaly and reduced volume of periventricular white matter [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This case contains all of these findings, further emphasising their commonality in RNU4-2 syndrome. In addition to these features, this case also features polymicrogyria, enlargement of the interpeduncular cistern and incomplete hippocampal inversion. These are new findings in RNU4-2 syndrome to the best of our knowledge.\u003c/p\u003e \u003cp\u003eThis case expands the neuroimaging phenotype of RNU4-2 syndrome, providing a detailed MRI assessment of a condition with limited imaging literature. Given that RNU4-2 syndrome is suspected to be a common neurogenetic disorder, it is important we add to the knowledge of its radiological findings. Further consolidating previously described imaging findings while describing new features adds to the education and awareness of this syndrome amongst radiologists and potentially aids in the identification of RNU4-2 syndrome in future cases.\u003c/p\u003e \u003cp\u003eIt is always important to interpret imaging findings as a collective with the aim of piecing together findings to a diagnosis or set of differential diagnoses. Identifying findings is the first step but this case highlights the importance of connecting individual imaging findings. Radiologists have a role in suggesting the possibility of neurogenetic disorders in cases such as this, potentially prompting genetic testing.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eRNU4-2 syndrome is a newly characterized condition in which neuroimaging plays a central diagnostic role. This case demonstrates distinctive imaging features of RNU4-2 syndrome which adds to the limited literature and may aid Radiologists making this diagnosis in children presenting with developmental delay and seizures.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors declare that they have no financial or non-financial interests that are directly or indirectly related to the work submitted for publication.\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details and images was obtained from the patient’s legal guardians.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eC.W. wrote the following sections of the manuscript: Abstract, introduction, imaging findings section, discussion and conclusion. S.Q. and A.E. wrote the clinical presentation and genetic testing sections of the manuscript.O.C. and C.W. both interpreted the images and came to consensus agreement on the findings.All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarbour K et al (2024) The face and features of RNU4-2: A new, common, recognizable, yet hidden neurodevelopmental disorder. Pediatr Neurol 161:188\u0026ndash;193. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pediatrneurol.2024.09.015\u003c/span\u003e\u003cspan address=\"10.1016/j.pediatrneurol.2024.09.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreene D et al (2024) Mutations in the U4 snrna gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders. Nat Med 30(8):2165\u0026ndash;2169. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41591-024-03085-5\u003c/span\u003e\u003cspan address=\"10.1038/s41591-024-03085-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValenzuela I et al (2024) Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome. Genet Sci 26(12):101288. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.gim.2024.101288\u003c/span\u003e\u003cspan address=\"10.1016/j.gim.2024.101288\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJackson A et al (2025) Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as Neurodevelopmental Disorder Genes. Nat Genet 57(6):1362\u0026ndash;1366. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41588-025-02209-y\u003c/span\u003e\u003cspan address=\"10.1038/s41588-025-02209-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Jonghe J et al (2025) \u003cem\u003eSaturation genome editing of RNU4\u0026ndash;2 reveals distinct dominant and recessive neurodevelopmental disorders\u003c/em\u003e [Preprint]. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1101/2025.04.08.25325442\u003c/span\u003e\u003cspan address=\"10.1101/2025.04.08.25325442\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"RNU4-2 syndrome, paediatric neuroradiology, neurodevelopmental disorders, magnetic resonance imaging","lastPublishedDoi":"10.21203/rs.3.rs-8737785/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8737785/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eRNU4-2\u0026ndash;related neurodevelopmental disorder (ReNU syndrome) is an emerging genetic condition associated with global developmental delay and seizures. Neuroimaging findings are increasingly recognized but remain incompletely characterized.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCase Presentation:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe describe a 3\u0026frac12;-year-old child presenting with seizure and a history developmental delay whose MRI demonstrated polymicrogyria, ventriculomegaly and dysgenesis of the corpus callosum. These findings, in conjunction with clinical and genetic assessment, supported the diagnosis of RNU4-2 syndrome.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis case highlights characteristic and potentially distinctive neuroimaging features of RNU4-2 syndrome, expanding the radiologic phenotype and potentially aiding early recognition in paediatric patients with seizures and developmental delay.\u003c/p\u003e","manuscriptTitle":"Imaging Findings in a Child with RNU4-2 (ReNU) Syndrome: A Paediatric Neuroradiology Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 16:38:09","doi":"10.21203/rs.3.rs-8737785/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba988888-14de-42fd-be78-cc58802f5c92","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-21T08:10:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 16:38:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8737785","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8737785","identity":"rs-8737785","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}