{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:29:59Z","timestamp":1783132199520,"version":"3.54.6"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background\/objectives<\/jats:title>\n                    <jats:p>\n                      Malan syndrome (MALNS) is a rare overgrowth disorder caused by pathogenic Nuclear Factor I\u2009\u00d7\u2009(\n                      <jats:italic>NFIX<\/jats:italic>\n                      ) gene variants, and characterized by postnatal overgrowth, macrocephaly, developmental delay, intellectual disability and distinctive facial features. Chiari type I malformation (CMI), a condition where the cerebellar tonsils extend below the foramen magnum, has been observed in some patients with MALNS, although the exact relationship between these disorders remains unclear. The objective of this case report is to describe a novel\n                      <jats:italic>NFIX<\/jats:italic>\n                      variant in a patient with MALNS and associated CMI. This case adds to the literature on\n                      <jats:italic>NFIX<\/jats:italic>\n                      variants in patients with CMI and underscores the potential benefit of early genetic testing for diagnosis and management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We describe a patient with clinical features consistent with MALNS, including macrocephaly, developmental delay, and typical craniofacial features. Brain Magnetic Resonance Imaging (MRI) revealed the presence of CMI. Genetic testing identified a novel heterozygous variant in\n                      <jats:italic>NFIX<\/jats:italic>\n                      , not previously described in the literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case contributes to the clinical and molecular characterization of MALNS by linking a previously unreported\n                      <jats:italic>NFIX<\/jats:italic>\n                      variant to CMI. The case underlines the importance to take into account MALNS in patients presenting with overgrowth and CMI. Furthermore, we report a novel variant to improve diagnostic accuracy and genotype-phenotype correlation. Indeed, timely molecular diagnosis is essential to differentiate among overgrowth syndromes and to establish appropriate long-term clinical follow-up.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1794137","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:05:23Z","timestamp":1775801123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel NFIX variant in a patient with Malan syndrome and associated Chiari type I malformation: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Michele","family":"Minerva","sequence":"first","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese","place":["Siena, Italy"]},{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Pinto","sequence":"additional","affiliation":[{"name":"Medical Genetics, Azienda Ospedaliera Universitaria Senese","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Toninelli","sequence":"additional","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Francioni","sequence":"additional","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Perilli","sequence":"additional","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese","place":["Siena, Italy"]},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa","place":["Genoa, Italy"]},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Laschi","sequence":"additional","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Lonoce","sequence":"additional","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese","place":["Siena, 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