{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:28:55Z","timestamp":1786631335557,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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. Neurol."],"abstract":"<jats:p>\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    monoallelic pathogenic variants account for up to 4% of genetically determined cerebral palsy cases, yet their phenotypic spectrum remains poorly defined. We retrospectively analyzed 25 individuals with pathogenic\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    variants using medical records and a questionnaire. Data included genetic variants, perinatal history, developmental milestones, behavioral characteristics, head growth, feeding, sleep difficulties, neurological and ophthalmological assessments. Brain MRIs were reviewed by expert neuroradiologists. Twenty-two distinct heterozygous variants were identified. Microcephaly occurred in 16\/22 patients. All exhibited global developmental delay, independent walking was achieved at a mean age of 2.1\u202fyears, with regression in 4\/16 independent walkers. Behavioral disorders were frequent, as were oral sensorimotor disorders (21\/25) and sleep disturbances (13\/21). Lower limb hypertonia was present in 22\/25 patients [spastic (8) and\/or dystonic (11)]. Unstable gait were common among ambulatory patients. Exaggerated startle reactions, often since birth, were reported in 16\/21. Exudative vitreoretinopathy was identified in 3\/5 patients with retinal angiography. Brain MRI (19 patients) showed: thickening of anterior commissure (8), frontal lobe hypoplasia (9), widening of superior vermian sulci (10) and corpus callosum anomalies (7). This study broadens the spectrum of\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    -related syndrome, reporting a complex motor phenotype combining (i) gait disturbances related to dystonic or non-dystonic hypertonia and unsteadiness, sometimes associated to dystonia in other body parts (ii) possible deterioration of motor achievements over the course of the disease (iii) an exaggerated startle reflex. New non-specific brain anomalies are precisely described. Our work underscores the need for registries and longitudinal studies to refine characterization and guide future therapies.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1754143","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:33:18Z","timestamp":1771392798000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CTNNB1-related disorders: clinical and radiological contributions from a French cohort"],"prefix":"10.3389","volume":"17","author":[{"given":"Eline","family":"Chauvet-Piat","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]},{"name":"Department of the Woman, Child and Adolescent, Geneva University Hospitals","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-C\u00e9line","family":"Fran\u00e7ois-Heude","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Manes","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, National Institute of Health and Medical Research (INSERM), University of Montpellier","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Coget","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Leboucq","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9r\u00e9nice","family":"Lecardonnel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidy","family":"Baide-Mairena","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Allais","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souad","family":"Touati","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirna","family":"Khalil","sequence":"additional","affiliation":[{"name":"Clinical Investigation Center Montpellier University Hospital","place":["Montpellier, INSERM, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"Chevassus","sequence":"additional","affiliation":[{"name":"Clinical Investigation Center Montpellier University Hospital","place":["Montpellier, INSERM, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, National Institute of Health and Medical Research (INSERM), University of Montpellier","place":["Montpellier, France"]},{"name":"Department of Neuroradiology, Montpellier University Hospital","place":["Montpellier, France"]},{"name":"Clinical Investigation Center Montpellier University Hospital","place":["Montpellier, INSERM, France"]},{"name":"Department of Clinical Genetics, Arnaud de Villeneuve Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Genevi\u00e8ve","sequence":"additional","affiliation":[{"name":"National Institute of Health and Medical Research (INSERM), Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Serrand","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, Montpellier University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Mazzola","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital","place":["Saint-Etienne, France"]},{"name":"NeuroPain Lab, Lyon Neuroscience Research Centre, French National Institute of Health and Medical Research, University of Lyon","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Dubard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Early Medico-Social Action Center (CAMSP)","place":["N\u00eemes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Renaud","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, University Hospital of Nancy","place":["Nancy, France"]},{"name":"Neurology Department, University Hospital of Nancy","place":["Nancy, France"]},{"name":"Facult\u00e9 de M\u00e9decine, Nutrition\u2013G\u00e9n\u00e9tique et Exposition aux Risques Environnementaux, Universit\u00e9 de Lorraine","place":["Nancy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Le Camus","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Toulouse University Hospital","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"More","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Charles Nicolle University Hospital","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Milh","sequence":"additional","affiliation":[{"name":"Pediatric Neurometabolic Department, Aix-Marseille University","place":["Marseille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Jean Minjoz University Hospital","place":["Besan\u00e7on, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ians-Bouteiller","family":"C\u00e9cile","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology and Rehabilitation, Bordeaux University Hospital","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Roubertie","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Montpellier University Hospital","place":["Montpellier, France"]},{"name":"Department of the Woman, Child and Adolescent, Geneva University Hospitals","place":["Geneva, Switzerland"]},{"name":"Institute for Neurosciences of Montpellier, National Institute of Health and Medical Research (INSERM), University of Montpellier","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1001\/jama.2020.26148","article-title":"Molecular diagnostic yield of exome sequencing in patients with cerebral palsy","volume":"325","author":"Moreno-De-Luca","year":"2021","journal-title":"JAMA"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1056\/NEJMoa1206524","article-title":"Diagnostic exome sequencing in persons with severe intellectual disability","volume":"367","author":"De Ligt","year":"2012","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1038\/s41588-020-0695-1","article-title":"Mutations disrupting neuritogenesis genes confer risk for cerebral palsy","volume":"52","author":"Jin","year":"2020","journal-title":"Nat Genet"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1143328","DOI":"10.3389\/fpsyt.2023.1143328","article-title":"CTNNB1 in neurodevelopmental disorders","volume":"14","author":"Zhuang","year":"2023","journal-title":"Front Psych"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"12564","DOI":"10.3390\/ijms232012564","article-title":"Correlation between phenotype and genotype in CTNNB1 syndrome: a systematic review of the literature","volume":"23","author":"Miro\u0161evi\u010d","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.1016\/j.gim.2022.08.006","article-title":"Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants","volume":"24","author":"Kayumi","year":"2022","journal-title":"Genet Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"107057","DOI":"10.1016\/j.parkreldis.2024.107057","article-title":"Movement disorder phenotype in CTNNB1-syndrome: a complex but recognizable phenomenology","volume":"126","author":"Garone","year":"2024","journal-title":"Parkinsonism Relat Disord"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3337","DOI":"10.1242\/jcs.013771","article-title":"Mechanistic insights from structural studies of \u03b2-catenin and its binding partners","volume":"120","author":"Xu","year":"2007","journal-title":"J Cell Sci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/ajmg.a.62504","article-title":"CTNNB1 -related neurodevelopmental disorder in a Chinese population: a case series","volume":"188","author":"Ho","year":"2022","journal-title":"Am J Med Genet A"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e090096","DOI":"10.1136\/bmjopen-2024-090096","article-title":"Unravelling age-related gait decline in cerebral palsy: insights into physiological changes and functional implications through an observational study\u2014a French study protocol in a laboratory setting","volume":"14","author":"Gravholt","year":"2024","journal-title":"BMJ Open"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12883-016-0554-y","article-title":"A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report","volume":"16","author":"Winczewska-Wiktor","year":"2016","journal-title":"BMC Neurol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"70498","DOI":"10.1002\/mdc3.70498","article-title":"Dystonia combined with startle is a syndromic clue for CTNNB1 -associated neurodevelopmental disorder","volume":"3","author":"Nagaratnam","year":"2026","journal-title":"Mov Disord Clin Pract"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s10803-025-06829-5","article-title":"Novel CTNNB1 gene variants in Spanish CTNNB1 syndrome patients: clinical and psychological manifestations","volume":"2025","author":"Pallar\u00e8s-Sastre","year":"2025","journal-title":"J Autism Dev Disord"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/cge.14487","article-title":"Clinical phenotypic spectrum of CTNNB1 neurodevelopmental disorder","volume":"105","author":"Sudnawa","year":"2024","journal-title":"Clin Genet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"113335","DOI":"10.1016\/j.isci.2025.113335","article-title":"An evolutionarily conserved role for CTNNB1\/\u03b2-CATENIN in regulating the development of the corpus callosum","volume":"28","author":"Parichha","year":"2025","journal-title":"iScience"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"180116","DOI":"10.1098\/rsob.180116","article-title":"Wnt signalling in the development of axon, dendrites and synapses","volume":"8","author":"He","year":"2018","journal-title":"Open Biol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/ar.22663","article-title":"Frontal brain expansion during development using MRI and Endocasts: relation to microcephaly and Homo floresiensis","volume":"296","author":"Vannucci","year":"2013","journal-title":"Anat Rec"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1046\/j.1469-0705.1998.11050317.x","article-title":"Microcephaly \u2013 no small deal","volume":"11","author":"Persutte","year":"1998","journal-title":"Ultrasound Obstet Gynecol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1111\/cge.14404","article-title":"Congenital heart defects in CTNNB1 syndrome: raising clinical awareness","volume":"104","author":"Sinibaldi","year":"2023","journal-title":"Clin Genet"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1007\/s00335-025-10105-3","article-title":"CTNNB1 syndrome mouse models","volume":"36","author":"Lain\u0161\u010dek","year":"2025","journal-title":"Mamm Genome"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"8467","DOI":"10.1523\/JNEUROSCI.0311-14.2014","article-title":"Stage-specific regulation of oligodendrocyte development by Wnt\/ -catenin signaling","volume":"34","author":"Dai","year":"2014","journal-title":"J Neurosci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.1523\/JNEUROSCI.4270-10.2011","article-title":"Wnt\/\u03b2-catenin signaling is an essential and direct driver of myelin gene expression and Myelinogenesis","volume":"31","author":"Tawk","year":"2011","journal-title":"J Neurosci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"176","DOI":"10.22608\/APO.201855","article-title":"Familial exudative vitreoretinopathy: pathophysiology, diagnosis, and management","volume":"7","author":"Tauqeer","year":"2018","journal-title":"Asia Pac J Ophthalmol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.ophtha.2013.08.010","article-title":"High prevalence of peripheral retinal vascular anomalies in family members of patients with familial exudative vitreoretinopathy","volume":"121","author":"Kashani","year":"2014","journal-title":"Ophthalmology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1001\/jamaophthalmol.2024.2847","article-title":"Vitreoretinopathy in asymptomatic children with CTNNB1 syndrome","volume":"142","author":"Bedoukian","year":"2024","journal-title":"JAMA Ophthalmol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1754143\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:35:57Z","timestamp":1786628157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1754143\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":26,"alternative-id":["10.3389\/fneur.2026.1754143"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1754143","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"article-number":"1754143"}}