{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:22:14Z","timestamp":1782379334846,"version":"3.54.5"},"reference-count":15,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017637","name":"Wroclaw University of Environmental and Life Sciences","doi-asserted-by":"crossref","award":["N110\/0003\/21"],"award-info":[{"award-number":["N110\/0003\/21"]}],"id":[{"id":"10.13039\/501100017637","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Ankylosis of the temporomandibular joint (TMJ) is a rare developmental disorder that involves fibrous or bony fusion within the joint. It is a severe structural and functional disorder. Typically, the phenotype manifests as joint immobilization and results in facial deformity and trismus. To date, ankylosis is rarely diagnosed as congenital and its occurrence mechanism has not been thoroughly understood. We observed a female patient who as a newborn showed slight facial asymmetry and impaired mandibular retraction. In addition, non-uniform occlusal fissures were noted; the lower part of the left earlobe was slightly smaller than the right earlobe. The aim of the work was the identification of pathogenic variants in the genome related to ankylosis. Ankylosis has no known causative gene yet; thus, Whole Exome Sequencing (WES) was performed. Materials and Methods: We observed a female patient with facial asymmetry and impaired mandibular retraction from birth. No phenotypic abnormalities were noted on the head or elsewhere on the body. A diagnostic computed tomography (CT) scan of the head performed at five months of age led to the diagnosis of congenital zygomatic-coronoid ankylosis. Genomic DNA samples were subjected to WES. Library preparation was carried out using the Twist Library Preparation EF Kit 2.0, followed by target enrichment with the Twist Exome 2.0 Plus Comprehensive Exome. Sequencing reads were aligned to the human reference genome (GRCh38), and variant calling was performed using standard bioinformatics workflows. Variants were subsequently filtered, annotated, and interpreted using VariantStudio. Assessment of variant pathogenicity was primarily based on comparisons with public databases, including ClinVar and VarSome, and was supported by in silico prediction tools such as SIFT and PolyPhen-2. Results: In genes responsible for disorders of the I and II pharyngeal arches, three pathogenic variants were identified: in the genes TCOF1 and POLR1B, responsible for the development of Treacher Collins syndrome (TCS), and one in the DHODH gene, responsible for Miller syndrome. Additionally, in genes that have not been linked so far with rare facial disorders, 42 variants were identified, of which 8 are listed as pathogenic. We present the first described patient with congenital ankylosis, who, although showing no phenotypic features of these syndromes, has identified pathogenic variants in genes responsible for craniofacial dysostosis. Conclusions: Variants in TCOF1, POLR1B and DHODH may represent candidate genetic factors associated with susceptibility to ankylosis. WES analysis is an appropriate method in the case of patients with congenital diseases with unknown genetic origin. In this study we provide a comprehensive list of all identified pathogenic variants. This might be useful for scientists searching for the genetic background of skeletal system issues, one of which could be bone and fibrous tissue remodeling.<\/jats:p>","DOI":"10.3390\/jcm15041403","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:15:12Z","timestamp":1770801312000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Congenital Temporomandibular Joint Ankylosis: Investigating Potential Genetic Etiologies with Whole Exome Sequencing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2635-1074","authenticated-orcid":false,"given":"Bo\u017cena Anna","family":"Marsza\u0142ek-Kruk","sequence":"first","affiliation":[{"name":"Department of Genetics, Wroclaw University of Environmental and Life Sciences, 51-631 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-2080","authenticated-orcid":false,"given":"Krzysztof","family":"Dowgierd","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, Collegium Medicum, University of Warmia and Mazury, 10-561 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1228-7534","authenticated-orcid":false,"given":"Mateusz","family":"Lejawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6026-0010","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Kulesa-Mrowiecka","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation in Internal Diseases, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4553-3479","authenticated-orcid":false,"given":"Wojciech","family":"Wola\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics, Faculty of Biomedical Engineering, Silesian University of Technology, 41-800 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-1156","authenticated-orcid":false,"given":"Andrzej","family":"My\u015bliwiec","sequence":"additional","affiliation":[{"name":"Laboratory of Physiotherapy and Physioprevention, Institute of Physiotherapy and Health Sciences, Academy of Physical Education in Katowice, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9182-6953","authenticated-orcid":false,"given":"Anna","family":"Lipowicz","sequence":"additional","affiliation":[{"name":"Department of Anthropology, Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1097\/PRS.0b013e3181ebe207","article-title":"Current concepts in pediatric temporomandibular joint disorders: Part 1. Etiology, epidemiology, and classification","volume":"126","author":"Allori","year":"2010","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jcms.2009.04.006","article-title":"Ankylosis of the temporomandibular joint","volume":"38","author":"Gundlach","year":"2010","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1001\/jama.1936.02770200025009","article-title":"Congenital bony temporomandibular ankylosis and facial hemiatrophy. Review of the literature and report of a case","volume":"106","author":"Burket","year":"1936","journal-title":"J. Am. Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Marsza\u0142ek-Kruk, B.A., W\u00f3jcicki, P., Dowgierd, K., and \u015amigiel, R. (2021). Treacher Collins Syndrome: Genetics, Clinical Features and Management. Genes, 12.","DOI":"10.3390\/genes12091392"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2186","DOI":"10.1002\/mgg3.2186","article-title":"Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population","volume":"11","author":"Yang","year":"2023","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1080\/09593985.2021.1952672","article-title":"Efficacy of immediate physiotherapy after surgical release of zygomatico-coronoid ankylosis in a young child: A case report","volume":"38","author":"Dowgierd","year":"2022","journal-title":"Physiother. Theory Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13005-024-00416-2","article-title":"The role of physiotherapy interventions in the management of temporomandibular joint ankylosis: A systematic review and meta-analysis","volume":"20","author":"Saini","year":"2024","journal-title":"Head Face Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dowgierd, K., Pokrowiecki, R., Kulesa-Mrowiecka, M., Dowgierd, M., Wo\u015b, J., Szymor, P., Kozakiewicz, M., Lipowicz, A., Roman, M., and My\u015bliwiec, A. (2022). Protocol for Multi-Stage Treatment of Temporomandibular Joint Ankylosis in Children and Adolescents. J. Clin. Med., 11.","DOI":"10.3390\/jcm11020428"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lipowicz, A., Wola\u0144ski, W., Kawlewska, E., Zwolska, P., Kulesa-Mrowiecka, M., Dowgierd, K., Linek, P., and My\u015bliwiec, A. (2021). Evaluation of Mandibular Growth and Symmetry in Child with Congenital Zygomatic-Coronoid Ankylosis. Symmetry, 13.","DOI":"10.3390\/sym13091634"},{"key":"ref_10","first-page":"159","article-title":"Morphometric assessment of mandibles with complications resulting from temporomandibular joint ankylosis in children from 4 months to 3 years of age","volume":"26","author":"Kawlewska","year":"2025","journal-title":"Acta Bioeng. Biomech."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server: Predicting effects of amino acid substitutions on proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Adzhubei, I., Jordan, D.M., and Sunyaev, S.R. (2013). Predicting functional effect of human missense mutations using PolyPhen-2. Curr. Protoc. Hum. Genet.","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1111\/ped.12562","article-title":"Nager syndrome and Pierre Robin sequence","volume":"57","author":"Rosa","year":"2015","journal-title":"Pediatr. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109842","DOI":"10.1016\/j.ijporl.2019.109842","article-title":"Associated syndromes in patients with Pierre Robin Sequence","volume":"131","author":"Karempelis","year":"2020","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/08869634.2021.1890453","article-title":"Physical therapy of temporomandibular disorder in a child with arthrogryposis multiplex congenita: A case report and literature review","volume":"42","author":"Piech","year":"2024","journal-title":"CRANIO"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:25:02Z","timestamp":1770960302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":15,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15041403"],"URL":"https:\/\/doi.org\/10.3390\/jcm15041403","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]}}}