{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:02:17Z","timestamp":1791280937003,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Oral Health"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder with physical, cognitive, and behavioral characteristics that is caused by heterozygous mutations in the <jats:italic>TCF4<\/jats:italic> gene. Patients with PTHS might present a unique challenge for oral healthcare professionals because of the associated comorbidities.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case report<\/jats:title>\n                <jats:p>Here we describe a new case of PTHS in a 13-year-old girl with particular emphasis on oro-dental findings and oral healthcare management. Observed oro-dental findings in our case included shallow palate, absence of lingual frenum, gingival enlargement, thick lips and relative microdontia. The patient was unable to tolerate dental care under local anesthesia. Therefore, comprehensive dental treatment was performed under general anesthesia after a careful pre-anesthetic cardio-respiratory, neurological, and hematological evaluation. The patient was closely monitored intra-operatively for breathing rhythm, O2 saturation, and signs of respiratory distress. The patient was observed for 24\u00a0h post-op for respiratory distress and was discharged then uneventfully.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Dental treatment under general anesthesia in these patients might be complicated by the abnormal breathing rhythm, and close monitoring and follow up for signs of respiratory distress after general anesthesia is necessary. Recognition of oral and dental findings might help to expand the phenotype and better characterize rare syndromes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12903-024-04296-5","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T15:02:37Z","timestamp":1716390157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the phenotype in Pitt-Hopkins syndrome; description of new oral finding and dental management considerations"],"prefix":"10.1186","volume":"24","author":[{"given":"Yazan","family":"Hassona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dua\u2019a","family":"Alqaisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Alkilani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iyas","family":"AbuHijleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"issue":"3","key":"4296_CR1","first-page":"182","volume":"14","author":"D -Pitt","year":"1978","unstructured":"Pitt D, Hopkins I. A syndrome of mental retardation, wide mouth and intermittent overbreathing. Aust Paediatr J. 1978;14(3):182\u20134.","journal-title":"Aust Paediatr J"},{"issue":"5","key":"4296_CR2","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1086\/515583","volume":"80","author":"C -Zweier","year":"2007","unstructured":"Zweier C, Peippo MM, Hoyer J, et al. Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). Am J Hum Genet. 2007;80(5):994\u20131001.","journal-title":"Am J Hum Genet"},{"issue":"5","key":"4296_CR3","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1086\/515582","volume":"80","author":"J -Amiel","year":"2007","unstructured":"Amiel J, Rio M, de Pontual L, et al. Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am J Hum Genet. 2007;80(5):988\u201393.","journal-title":"Am J Hum Genet"},{"issue":"12","key":"4296_CR4","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1093\/hmg\/ddm099","volume":"16","author":"A -Brockschmidt","year":"2007","unstructured":"Brockschmidt A, Todt U, Ryu S, et al. Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. Hum Mol Genet. 2007;16(12):1488\u201394.","journal-title":"Hum Mol Genet"},{"key":"4296_CR5","unstructured":"GeneRIF. (TCF4 transcription factor 4 [Homo sapiens (human)] - Gene - NCBI (nih.gov)); https:\/\/www.ncbi.nlm.nih.gov\/gene?Db=gene&Cmd=DetailsSearch&Term=6925 (accessed 10.11.2023)."},{"issue":"11","key":"4296_CR6","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1111\/ejn.14674","volume":"51","author":"M -Schoof","year":"2020","unstructured":"Schoof M, Hellwig M, Harrison L, et al. The basic helix-loop-helix transcription factor TCF4 impacts brain architecture as well as neuronal morphology and differentiation. Eur J Neurosci. 2020;51(11):2219\u201335.","journal-title":"Eur J Neurosci"},{"issue":"6","key":"4296_CR7","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1111\/cge.14206","volume":"102","author":"B -Popp","year":"2022","unstructured":"Popp B, Bienvenu T, Giurgea I, et al. The recurrent TCF4 missense variant p.(Arg389Cys) causes a neurodevelopmental disorder overlapping with but not typical for Pitt-Hopkins syndrome. Clin Genet. 2022;102(6):517\u201323.","journal-title":"Clin Genet"},{"issue":"3","key":"4296_CR8","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1177\/0883073817750490","volume":"33","author":"K -Goodspeed","year":"2018","unstructured":"Goodspeed K, Newsom C, Morris MA, et al. Pitt-Hopkins syndrome: a review of current literature, Clinical Approach, and 23-Patient Case Series. J Child Neurol. 2018;33(3):233\u201344.","journal-title":"J Child Neurol"},{"issue":"3\u20135","key":"4296_CR9","first-page":"171","volume":"2","author":"M -Peippo","year":"2012","unstructured":"Peippo M, Ignatius J. Pitt-Hopkins Syndrome. Mol Syndromol. 2012;2(3\u20135):171\u201380.","journal-title":"Mol Syndromol"},{"issue":"2","key":"4296_CR10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1097\/01.mcd.0000184973.14775.32","volume":"15","author":"MM -Peippo","year":"2006","unstructured":"Peippo MM, Simola KO, Valanne LK, et al. Pitt-Hopkins syndrome in two patients and further definition of the phenotype. Clin Dysmorphol. 2006;15(2):47\u201354.","journal-title":"Clin Dysmorphol"},{"issue":"7","key":"4296_CR11","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1002\/ajmg.a.34070","volume":"155A","author":"G -Marangi","year":"2011","unstructured":"Marangi G, Ricciardi S, Orteschi D, et al. The Pitt-Hopkins syndrome: report of 16 new patients and clinical diagnostic criteria. Am J Med Genet A. 2011;155A(7):1536\u201345.","journal-title":"Am J Med Genet A"},{"issue":"3","key":"4296_CR12","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/(SICI)1096-8628(19980123)75:3<273::AID-AJMG9>3.0.CO;2-R","volume":"75","author":"ID -Van Balkom","year":"1998","unstructured":"Van Balkom ID, Quartel S, Hennekam RC. Mental retardation, coarse face, and hyperbreathing: confirmation of the Pitt-Hopkins syndrome. Am J Med Genet. 1998;75(3):273\u20136.","journal-title":"Am J Med Genet"},{"issue":"7","key":"4296_CR13","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1002\/ajmg.a.34055","volume":"155A","author":"D -Lehalle","year":"2011","unstructured":"Lehalle D, Williams C, Siu VM, et al. Fetal pads as a clue to the diagnosis of Pitt-Hopkins syndrome. 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Clin Genet. 2019;95(4):462\u201378.","journal-title":"Clin Genet"},{"issue":"4","key":"4296_CR16","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/scd.12689","volume":"42","author":"D -Alqaisi","year":"2022","unstructured":"Alqaisi D, Hassona Y. Oral findings and healthcare management in Shashi-Pena syndrome. Spec Care Dentist. 2022;42(4):432\u20136.","journal-title":"Spec Care Dentist"},{"issue":"4","key":"4296_CR17","doi-asserted-by":"publisher","first-page":"269","DOI":"10.2165\/11530090-000000000-00000","volume":"11","author":"L -Machet","year":"2010","unstructured":"Machet L, H\u00fcttenberger B, Georgesco G, Dor\u00e9 C, Jamet F, Bonnin-Goga B, Giraudeau B, Maruani A, Laure B, Vaillant L. Absence of inferior labial and lingual frenula in Ehlers-Danlos syndrome: a minor diagnostic criterion in French patients. Am J Clin Dermatol. 2010;11(4):269\u201373. https:\/\/doi.org\/10.2165\/11530090-000000000-00000.","journal-title":"Am J Clin Dermatol"},{"issue":"2","key":"4296_CR18","first-page":"126","volume":"6","author":"PA -Ghafoor","year":"2014","unstructured":"Ghafoor PA, Rafeeq M, Dubey A. Assessment of oral side effects of antiepileptic drugs and traumatic oro-facial injuries encountered in epileptic children. J Int Oral Health. 2014;6(2):126\u20138.","journal-title":"J Int Oral Health"},{"issue":"1","key":"4296_CR19","doi-asserted-by":"publisher","first-page":"70","DOI":"10.2174\/1871529X15666150108115241","volume":"15","author":"J -Hirschfeld","year":"2015","unstructured":"Hirschfeld J, Kawai T. Oral inflammation and bacteremia: implications for chronic and acute systemic diseases involving major organs. 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No approval was therefore needed.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Experimental protocols"}},{"value":"None declared.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"597"}}