{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:20:50Z","timestamp":1778178050853,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Noonan syndrome is a relatively common genetic syndrome with clinical and genetic heterogeneity. Besides the characteristic features such as short stature, typical facial features, congenital heart defects, skeletal and ocular anomalies, various orodental manifestations occur with variable frequency. High-arched palate, malocclusions, micrognathism, giant cell lesions, and anomalous lateral incisors are frequently observed features, whereas supernumerary teeth, hypodontia, macrodontia, enamel hypoplasia, severe dental caries, impacted teeth, delayed eruption, taurodontism and odontoma have occasionally been reported. Here, we present a family with three affected members displaying variable dental manifestations carrying the same PTPN11 c.178G&gt;A pathogenic variant. A 14-year-old and a 12-year-old, both female patients, presented high-arched palates, delayed dental eruption and caries. Moreover, the younger sibling exhibited frequently observed manifestations such as malocclusion and gingivitis, and further rare features like open-bite, micrognathia, and crowded teeth were present. The mother of the patients had periodontitis and enamel problems. Monitoring the oral health of the patients with NS is important, as they are prone to severe dental caries, gingival and other orodental problems. Therefore, initiating early orodental examination is highly recommended for patients with suspicion or diagnosis of NS.<\/jats:p>","DOI":"10.3390\/ijms262311414","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"11414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heterogeneity of Orodental Features in a Family with Noonan Syndrome"],"prefix":"10.3390","volume":"26","author":[{"given":"Gr\u00e9ta","family":"Antal","sequence":"first","affiliation":[{"name":"Department of Dentistry, Oral and Maxillofacial Surgery, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Csabai","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Oral and Maxillofacial Surgery, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Zsigmond","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildiko","family":"Szanto","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Oral and Maxillofacial Surgery, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2303-1670","authenticated-orcid":false,"given":"Kinga","family":"Hadzsiev","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-6244","authenticated-orcid":false,"given":"Judit","family":"Bene","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1136\/adc.67.2.178","article-title":"A clinical study of Noonan syndrome","volume":"67","author":"Sharland","year":"1992","journal-title":"Arch. Dis. Child."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.genom.6.080604.162305","article-title":"Noonan syndrome and related disorders: Genetics and pathogenesis","volume":"6","author":"Tartaglia","year":"2005","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/ajmg.a.30598","article-title":"Genotypic and phenotypic characterization of Noonan syndrome: New data and review of the literature","volume":"134A","author":"Jongmans","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1136\/archdischild-2021-322858","article-title":"Noonan syndrome: Improving recognition and diagnosis","volume":"107","author":"Zenker","year":"2022","journal-title":"Arch. Dis. Child."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/adc.2006.104547","article-title":"The natural history of Noonan syndrome: A long-term follow-up study","volume":"92","author":"Shaw","year":"2007","journal-title":"Arch. Dis. Child."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.beem.2010.09.002","article-title":"Noonan syndrome and clinically related disorders","volume":"25","author":"Tartaglia","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/ocr.12144","article-title":"A review of craniofacial and dental findings of the RASopathies","volume":"20","author":"Cao","year":"2017","journal-title":"Orthod. Craniofacial Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1136\/jmg.2007.050450","article-title":"Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS\/MAPK signalling pathway: Genotype-phenotype relationships and overlap with Costello syndrome","volume":"44","author":"Nava","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0140-6736(12)61023-X","article-title":"Noonan syndrome","volume":"381","author":"Roberts","year":"2013","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/jhg.2015.114","article-title":"Recent advances in RASopathies","volume":"61","author":"Aoki","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijpam.2016.06.003","article-title":"Noonan syndrome-causing genes: Molecular update and an assessment of the mutation rate","volume":"3","author":"Belhassan","year":"2016","journal-title":"Int. J. Pediatr. Adolesc. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/ajmg.a.62046","article-title":"Craniofacial and occlusal features of children with Noonan syndrome","volume":"185","author":"Bagattoni","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jcms.2020.01.011","article-title":"Dental and maxillofacial features of Noonan Syndrome: Case series of ten patients","volume":"48","author":"Lutz","year":"2020","journal-title":"J. Cranio-Maxillo-Facial Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2334\/josnusd.51.301","article-title":"Noonan syndrome: A case report","volume":"51","author":"Emral","year":"2009","journal-title":"J. Oral Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"197","DOI":"10.17796\/jcpd.36.2.81074271088334h2","article-title":"Atypical orofacial conditions in Noonan syndrome: A case report","volume":"36","author":"Toureno","year":"2011","journal-title":"J. Clin. Pediatr. Dent."},{"key":"ref_16","first-page":"468","article-title":"Associated noncardiac malformation in children with congenital heart disease","volume":"63","year":"1963","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"317","DOI":"10.4103\/2141-9248.160190","article-title":"Multiple Unerupted Permanent Teeth Associated with Noonan Syndrome","volume":"5","author":"Uloopi","year":"2015","journal-title":"Ann. Med. Health Sci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/scd.12780","article-title":"Oral manifestations of eleven individuals with Noonan syndrome. A case series","volume":"43","author":"Vavetsi","year":"2023","journal-title":"Spec. Care Dent."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"262","DOI":"10.17796\/1053-4625-44.4.8","article-title":"Orodental, Facial and Clinical Features of Mutation-Positive Noonan Syndrome: A Monocentric Study","volume":"44","author":"Hazan","year":"2020","journal-title":"J. Clin. Pediatr. Dent."},{"key":"ref_20","first-page":"1503","article-title":"Oral manifestations of Noonan syndrome: Review of the literature and a report of four cases","volume":"55","author":"Mallineni","year":"2014","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Janas-Naze, A., Malkiewicz, K., and Zhang, W. (2022). Clinical Findings in Children with Noonan Syndrome-A 17-Year Retrospective Study in an Oral Surgery Center. Children, 9.","DOI":"10.3390\/children9101486"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/sj.ejhg.5200915","article-title":"PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning","volume":"11","author":"Schollen","year":"2003","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejmg.2006.08.003","article-title":"Mild variable Noonan syndrome in a family with a novel PTPN11 mutation","volume":"50","author":"Zenker","year":"2007","journal-title":"Eur. J. Med. Genet."},{"key":"ref_24","first-page":"76","article-title":"Clinical Variability in a Family with Noonan Syndrome with a Homozygous PTPN11 Gene Variant in Two Individuals","volume":"16","author":"Yildirim","year":"2024","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/ng772","article-title":"Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome","volume":"29","author":"Tartaglia","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Solman, M., Woutersen, D.T.J., and den Hertog, J. (2022). Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1046415"},{"key":"ref_27","first-page":"136","article-title":"Etiopathogenic analysis of the caries on three patients with Noonan Syndrome","volume":"8","year":"2003","journal-title":"Med. Oral"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ejmg.2008.05.003","article-title":"The genetic basis of inherited anomalies of the teeth. Part 2: Syndromes with significant dental involvement","volume":"51","author":"Berdal","year":"2008","journal-title":"Eur. J. Med. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Salerno, C., D\u2019Avola, V., Oberti, L., Almonte, E., Bazzini, E.M., Tartaglia, G.M., and Cagetti, M.G. (2021). Rare Genetic Syndromes and Oral Anomalies: A Review of the Literature and Case Series with a New Classification Proposal. Children, 9.","DOI":"10.3390\/children9010012"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1611768","DOI":"10.3389\/pore.2024.1611768","article-title":"Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: The importance of genetic analysis in the early diagnosis","volume":"30","author":"Antal","year":"2024","journal-title":"Pathol. Oncol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1542\/peds.2009-3207","article-title":"Noonan syndrome: Clinical features, diagnosis, and management guidelines","volume":"126","author":"Romano","year":"2010","journal-title":"Pediatrics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:08:41Z","timestamp":1764151721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":31,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311414"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311414","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}