{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:40:14Z","timestamp":1790278814327,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Natural Science Foundation of Guangdong Province","award":["2023A1515140149"],"award-info":[{"award-number":["2023A1515140149"]}]},{"name":"National Key Research and Development Program of China","award":["2022YFC270330"],"award-info":[{"award-number":["2022YFC270330"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      To elucidate the prenatal diagnostic challenges, genetic landscape, and clinical outcomes of Treacher Collins syndrome (TCS), focusing on the role of\n                      <jats:italic>TCOF1<\/jats:italic>\n                      variants, prenatal ultrasound findings, and counselling implications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic literature review (2000\u20132025) identified 273 TCS cases, supplemented by two index cases(one from each of two unrelated families) from our centre. Data included genetic testing (whole-exome sequencing, Sanger sequencing), prenatal imaging, and clinical outcomes. Variants in\n                      <jats:italic>TCOF1<\/jats:italic>\n                      were analyzed alongside genotype-phenotype correlations and mosaicism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We assembled 275 patients in total, including 273 cases from the literature and two index cases from our centre. We summarized 15 individuals with prenatal ultrasound assessment and\/or pregnancy outcomes(2 from our centre and 13 from the literature). Across 303 TCOF1 variant entries extracted from the included reports frameshift changes were most frequent at 66.01%, followed by nonsense variants at 10.56%, with missense, large deletions, and splice variants comprising the remainder. Pathogenic\n                      <jats:italic>TCOF1<\/jats:italic>\n                      variants were dominated by frameshift and nonsense changes, and truncations in later exons, for example exon 24, were enriched among severe phenotypes; overall, 68 of 275 cases, that is, 24.73%, were categorized as severe. Parental mosaicism was identified or suspected in 6 of the 275 cases (2.18%), including low-level paternal mosaicism confirmed in blood and semen in one family. Termination of pregnancy (ToP) occurred in 6 cases within this prenatal findings dataset, attributable to severe airway risks or parental choice. Postnatal management (airway support, hearing aids, reconstructive surgery) supported survival in 263\/275 (95.64%) of all reported cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prenatal diagnosis of TCS relies on ultrasound detection of craniofacial anomalies and gene testing, but severity prediction remains challenging due to mosaicism and variable expressivity. Low-level parental mosaicism materially affects recurrence-risk counselling and should be actively considered when a foetal variant appears de novo. Early genetic diagnosis and personalized counselling are crucial for effective TCS management, helping families navigate medical, ethical, and sociocultural concerns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04094-4","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:15:11Z","timestamp":1773918911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating imaging and genomics in prenatal Treacher Collins syndrome: evidence for practice and policy"],"prefix":"10.1186","volume":"21","author":[{"given":"Chunling","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhi","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanling","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"4094_CR1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/cge.14243","volume":"103","author":"ZS Ulhaq","year":"2023","unstructured":"Ulhaq ZS, Nurputra DK, Soraya GV, Kurniawati S, Istifiani LA, Pamungkas SA, Tse W. A systematic review on treacher Collins syndrome: correlation between molecular genetic findings and clinical severity. Clin Genet. 2023;103:146\u201355.","journal-title":"Clin Genet"},{"key":"4094_CR2","doi-asserted-by":"crossref","unstructured":"Marszalek-Kruk BA, Wojcicki P, Dowgierd K, Smigiel R. Treacher Collins syndrome: genetics, clinical features and management. Genes-Basel. 2021;12.","DOI":"10.3390\/genes12091392"},{"key":"4094_CR3","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1055\/s-0035-1568139","volume":"31","author":"S Bartel-Friedrich","year":"2015","unstructured":"Bartel-Friedrich S. Congenital auricular malformations: description of anomalies and syndromes. 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Written informed consent was obtained from all participants or their legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics and consent to publish"}},{"value":"The authors declared no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"99"}}