{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:35:47Z","timestamp":1786642547798,"version":"build-2736575974"},"reference-count":22,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Regulatory Factor X3 (RFX3\u2014OMIM#601337) encodes a transcription factor that is highly expressed in the human brain, particularly during neurodevelopment. It has been previously associated with neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual developmental disorder, and attention-deficit\/hyperactivity disorder. However, the neurological and epileptic features remain poorly characterized, and no phenotype has yet been formally annotated in OMIM. Here, we report the second known case of Infantile Epileptic Spasms Syndrome (IESS) associated with RFX3 variants. The patient developed clusters of extensor spasms associated with eye deviation and achieved complete remission within two weeks following vigabatrin and ACTH therapy, remaining seizure-free thereafter. During follow-up, he presented with global developmental delay, ASD, and facial dysmorphisms. Genetic analysis by array comparative genomic hybridization identified a de novo heterozygous microdeletion of approximately 147 kb at 9p24.2, involving the initial exons of RFX3 (NM_134428). This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption. It highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.<\/jats:p>","DOI":"10.3390\/ijms27167238","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:01:35Z","timestamp":1786640495000},"page":"7238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RFX3 Pathogenic Variants as a Rare Cause of Infantile Epileptic Spasms Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2627-6483","authenticated-orcid":false,"given":"Graziana","family":"Ceraolo","sequence":"first","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Human Pathology of the Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6714-6952","authenticated-orcid":false,"given":"Giulia","family":"Spoto","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Biomedical Sciences, Dental Sciences & Morpho\u2014Functional Imaging, University of Messina, 98125 Messina, Italy"},{"name":"IRCCS Centro Neurolesi Bonino-Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Trivisano","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesu\u2019 Children\u2019s Hospital IRCCS, EpiCARE, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Federico","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-8510","authenticated-orcid":false,"given":"Mirella","family":"Vinci","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-8223","authenticated-orcid":false,"given":"Francesco","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"},{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-9991","authenticated-orcid":false,"given":"Simone","family":"Treccarichi","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-3365","authenticated-orcid":false,"given":"Antonino","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2014IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Di Rosa","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Biomedical Sciences, Dental Sciences & Morpho\u2014Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-0287","authenticated-orcid":false,"given":"Nicola","family":"Specchio","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesu\u2019 Children\u2019s Hospital IRCCS, EpiCARE, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Gennaro","family":"Nicotera","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Maternal-Infantile Department, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sugiaman-Trapman, D., Vitezic, M., Jouhilahti, E.M., Mathelier, A., Lauter, G., Misra, S., Daub, C.O., Kere, J., and Swoboda, P. 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