{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:48:34Z","timestamp":1763390914696,"version":"3.45.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background:\u00a0TCF20-associated neurodevelopmental disorder (TCF20-NDD) is a heterogeneous clinical condition resulting from defects in gene-encoding Transcription Factor 20, which plays a key role in neuronal development and synaptic function. Here, we present a novel case involving an 11-year-old boy who was referred to us for a neuro-developmental disorder characterized by attention deficit hyperactivity disorder (ADHD), tremor in the upper limbs, tilted head posture, motor delay, impaired executive functioning, and oculomotor dyspraxia. Methods: Genetic tests were performed, including CGH array, molecular analysis of the FMR1 gene, molecular analysis using a next-generation sequencing gene panel targeted for spinocerebellar diseases, and finally, WES including mitochondrial genome analysis. A neuroimaging study of brain and spine was performed using MRI. Results: Trio Whole Exome Sequencing revealed a de novo pathogenic frameshift variant NM_001378418.1:c.5009dup, p.(Thr1671Aspfs*5) in the TCF20 gene. The MRI scan of the brain, cervical, dorsal, and lumbosacral spine revealed Chiari type I malformation. Regarding the pathogenic mechanism underlying Chiari I malformation, it could be found in the homology between TCF20 and the RAI1 gene, the latter being associated with alterations in the posterior cranial fossa. Conclusions: We emphasize the use of exome sequencing in patients with unclear clinical presentations, with awareness of TCF20-associated neurodevelopmental disorder; paying attention to brain MRI findings would be useful to further expand the phenotype of TCF20-NDD.<\/jats:p>","DOI":"10.3390\/children12111543","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T16:46:22Z","timestamp":1763138782000},"page":"1543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Boy with a Novel Variant in TCF20: An Expanded Phenotype and a Brief Review of the Literature"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4588-0084","authenticated-orcid":false,"given":"Diletta","family":"Ziveri","sequence":"first","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0092-5604","authenticated-orcid":false,"given":"Carlo Alberto","family":"Cesaroni","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Laboratorio di Neurofisiologia Pediatrica, Dipartimento Materno-Infantile, Azienda USL-IRCCS Di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-755X","authenticated-orcid":false,"given":"Gianluca","family":"Contr\u00f2","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-7854","authenticated-orcid":false,"given":"Stefano Giuseppe","family":"Caraffi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ormitti","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucrezia","family":"Giannini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Medical Genetics Unit, IRCCS Azienda Ospedaliera Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1501-0146","authenticated-orcid":false,"given":"Agnese","family":"Pantani","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5976-1873","authenticated-orcid":false,"given":"Anna","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-9722","authenticated-orcid":false,"given":"Susanna","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9865-0751","authenticated-orcid":false,"given":"Marzia","family":"Pollazzon","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Frattini","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-0952","authenticated-orcid":false,"given":"Carlo","family":"Fusco","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Dipartimento Materno-Infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Laboratorio di Neurofisiologia Pediatrica, Dipartimento Materno-Infantile, Azienda USL-IRCCS Di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","first-page":"2036","article-title":"Variants in TCF20 in neurodevelopmental disability: Description of 27 new patients and review of literature","volume":"21","author":"Torti","year":"2019","journal-title":"Anesth. 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