{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:57:52Z","timestamp":1780516672149,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency ARRS","doi-asserted-by":"publisher","award":["MR-39262"],"award-info":[{"award-number":["MR-39262"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency ARRS","doi-asserted-by":"publisher","award":["Z1-3193"],"award-info":[{"award-number":["Z1-3193"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency ARRS","doi-asserted-by":"publisher","award":["P4-0176"],"award-info":[{"award-number":["P4-0176"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency ARRS","doi-asserted-by":"publisher","award":["J7-4537"],"award-info":[{"award-number":["J7-4537"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The CTNNB1 Syndrome is a rare neurodevelopmental disorder associated with developmental delay, intellectual disability, and delayed or absent speech. The aim of the present study is to systematically review the available data on the prevalence of clinical manifestations and to evaluate the correlation between phenotype and genotype in published cases of patients with CTNNB1 Syndrome. Studies were identified by systematic searches of four major databases. Information was collected on patients\u2019 genetic mutations, prenatal and neonatal problems, head circumference, muscle tone, EEG and MRI results, dysmorphic features, eye abnormalities, early development, language and comprehension, behavioral characteristics, and additional clinical problems. In addition, the mutations were classified into five groups according to the severity of symptoms. The study showed wide genotypic and phenotypic variability in patients with CTNNB1 Syndrome. The most common moderate-severe phenotype manifested in facial dysmorphisms, microcephaly, various motor disabilities, language and cognitive impairments, and behavioral abnormalities (e.g., autistic-like or aggressive behavior). Nonsense and missense mutations occurring in exons 14 and 15 were classified in the normal clinical outcome category\/group because they had presented an otherwise normal phenotype, except for eye abnormalities. A milder phenotype was also observed with missense and nonsense mutations in exon 13. The autosomal dominant CTNNB1 Syndrome encompasses a wide spectrum of clinical features, ranging from normal to severe. While mutations cannot be more generally categorized by location, it is generally observed that the C-terminal protein region (exons 13, 14, 15) correlates with a milder phenotype.<\/jats:p>","DOI":"10.3390\/ijms232012564","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T22:19:53Z","timestamp":1666217993000},"page":"12564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-0607","authenticated-orcid":false,"given":"\u0160pela","family":"Miro\u0161evi\u010d","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Medical Faculty Ljubljana, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7478-3536","authenticated-orcid":false,"given":"Shivang","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur 342027, Rajasthan, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Su\u0161jan","sequence":"additional","affiliation":[{"name":"Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"\u017dakelj","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-3459","authenticated-orcid":false,"given":"David","family":"Gosar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2469-6335","authenticated-orcid":false,"given":"Vida","family":"Forstneri\u010d","sequence":"additional","affiliation":[{"name":"Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du\u0161ko","family":"Lain\u0161\u010dek","sequence":"additional","affiliation":[{"name":"Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6337-5251","authenticated-orcid":false,"given":"Roman","family":"Jerala","sequence":"additional","affiliation":[{"name":"Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia"},{"name":"EN-FIST Centre of Excellence, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-420X","authenticated-orcid":false,"given":"Damjan","family":"Osredkar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Center for Developmental Neuroscience, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","first-page":"487","article-title":"A de novo CTNNB1 Novel Splice Variant in an Adult Female with Severe Intellectual Disability","volume":"13","author":"Verhoeven","year":"2020","journal-title":"Int. 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