{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:14:04Z","timestamp":1789413244110,"version":"build-2803163510"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"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":["Ital J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Hereditary Hemorrhagic Telangiectasia (HHT) is a rare, hereditary, autosomal dominant vascular disease, characterized by visceral arteriovenous malformations (AVMs), mucocutaneous telangiectasias and epistaxis. While symptomatic medical and surgical therapies are used in the management of pediatric patients, data comparing phenotypic presentation between genetically related individuals (e.g., parent-child pairs) remain limited.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Aims and Methods<\/jats:title>\n            <jats:p>We conducted a single-center retrospective study involving pediatric patients with genetically confirmed HHT and their affected parents at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy. The aim of our study was to assess genotype-phenotype correlation and intrafamilial HHT-phenotypic variability. Clinical, laboratory, imaging, and therapeutic data were collected between May 2022 and May 2023. Variables including presence of AVMs, epistaxis, telangiectasias, anemia, and need for interventions were compared between children and their parents.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The study included 11 children (mean age 11.8 years) and 9 adults (mean age 47 years), all exhibiting <jats:italic>ENG<\/jats:italic> or <jats:italic>ACVRL1<\/jats:italic> variants. While epistaxis was common in both cohorts (91% in children vs. 100% in adults), mucocutaneous telangiectasias and AVMs were more prevalent in adults. AVMs were more frequently detected in adults, especially among <jats:italic>ENG<\/jats:italic> carriers. Notably, phenotype concordance between parent-child pairs with the same mutation was observed in only 3 up to 9 families (33.3%), with substantial intrafamilial variability in AVM distribution and disease severity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our findings confirm the variable expressivity of HHT, even among first-degree relatives sharing the same pathogenic variant. No consistent overlap was observed between parent and child phenotypes, reinforcing the need for individualized pediatric screening and follow-up. Early genetic testing remains essential to prevent complications and guide appropriate management.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13052-025-02087-4","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:53:38Z","timestamp":1758736418000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Family phenotypic profile in hereditary hemorrhagic telangiectasia: genotype-phenotype correlation in a pediatric Italian population"],"prefix":"10.1186","volume":"51","author":[{"given":"Valentina","family":"Giorgio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Di Foggia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-5630","authenticated-orcid":false,"given":"Giovanna","family":"Quatrale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Margiotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Stella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Proli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Leoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Onesimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio Cesare","family":"Passali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Contegiacomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Zampino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela Lucci","family":"Cordisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sonnini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Gaetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"2087_CR1","volume-title":"Hereditary hemorrhagic telangiectasia","author":"A Guttmacher","year":"2007","unstructured":"Guttmacher A, Marchuck D, Pyeritz RE. Hereditary hemorrhagic telangiectasia. 5th ed. Philadelphia: Churchill Livingstone; 2007.","edition":"5"},{"issue":"7","key":"2087_CR2","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/GIM.0b013e3182136d32","volume":"13","author":"J McDonald","year":"2011","unstructured":"McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med. 2011;13(7):607\u201316.","journal-title":"Genet Med"},{"key":"2087_CR3","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1111\/j.1365-2516.2008.01774.x","volume":"14","author":"AA Sharathkumar","year":"2008","unstructured":"Sharathkumar AA, Shapiro A. Hereditary haemorrhagic telangiectasia. 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Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia. Ann Intern Med. 2020;173(12):989\u20131001. https:\/\/doi.org\/10.7326\/M20-1443. Epub 2020 Sep 8. PMID: 32894695.","journal-title":"Ann Intern Med"},{"issue":"9","key":"2087_CR7","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.3390\/jcm9092714","volume":"9","author":"A Kilian","year":"2020","unstructured":"Kilian A, Latino GA, White AJ, et al. Genotype-Phenotype correlations in children with HHT. J Clin Med. 2020;9(9):2714. https:\/\/doi.org\/10.3390\/jcm9092714. PMID: 32842615; PMCID: PMC7565052.","journal-title":"J Clin Med"},{"key":"2087_CR8","doi-asserted-by":"publisher","unstructured":"Pahl KS, Choudhury A, Wusik K et al. Applicability of the Cura\u00e7ao Criteria for the Diagnosis of Hereditary Hemorrhagic Telangiectasia in the Pediatric Population. J Pediatr. 2018;197:207\u2013213. https:\/\/doi.org\/10.1016\/j.jpeds.2018.01.079. Epub 2018 Apr 11. 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Iron deficiency in infants and children\u2009<\u200912 years: Screening, prevention, clinical manifestations, and diagnosis, In:UpToDateaccessed on December 15, (2023)."},{"key":"2087_CR12","unstructured":"ABIM Laboratory. Test Reference Ranges \u0336 July 2023."},{"key":"2087_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fgene.2015.00001","volume":"6","author":"J McDonald","year":"2015","unstructured":"McDonald J, Wooderchak-Donahue W, VanSant Webb C, et al. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era. Front Genet. 2015;6:1.","journal-title":"Front Genet"},{"key":"2087_CR14","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3174\/ajnr.A4980","volume":"38","author":"GJ Palagallo","year":"2017","unstructured":"Palagallo GJ, McWilliams SR, Sekarski LA, et al. The prevalence of malformations of cortical development in a pediatric hereditary hemorrhagic telangiectasia population. AJNR Am J Neuroradiol. 2017;38:383\u20136.","journal-title":"AJNR Am J Neuroradiol"},{"key":"2087_CR15","unstructured":"Bergerot JF, Dupuis-Girod S, Berthezene Y et al. Malformations of cortical de- velopment and brain vessels in patients with hereditary haemorrhagic telangiectasia. In: 10th International Hereditary Hemorrhagic Telangiectasia Scientific Conference; Cork, Ireland; June 12\u201315, 2013."},{"issue":"1","key":"2087_CR16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1212\/WNL.0000000000006686","volume":"92","author":"JM Klostranec","year":"2019","unstructured":"Klostranec JM, Chen L, Mathur S, McDonald J, Faughnan ME, Ratjen F, Krings T. A theory for polymicrogyria and brain arteriovenous malformations in HHT. Neurology. 2019;92(1):34\u201342. PMID: 30584075; PMCID: PMC6336165.","journal-title":"Neurology"},{"key":"2087_CR17","doi-asserted-by":"crossref","unstructured":"Kasthuri RS, Montifar M, Nelson J et al. Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia. Am J Hematol. 2017 Jun 22.","DOI":"10.1002\/ajh.24832"},{"key":"2087_CR18","doi-asserted-by":"publisher","unstructured":"Lenato GM, Guanti G. Hereditary Haemorrhagic Telangiectasia (HHT): genetic and molecular aspects. Curr Pharm Des. 2006;12(10):1173-93. https:\/\/doi.org\/10.2174\/138161206776361291. PMID: 16611099.","DOI":"10.2174\/138161206776361291"},{"issue":"10","key":"2087_CR19","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.3390\/jcm11102685","volume":"11","author":"E Gaetani","year":"2022","unstructured":"Gaetani E, Peppucci E, Agostini F, Di Martino L, Lucci Cordisco E, Sturiale CL, Puca A, Porfidia A, Alexandre A, Pedicelli A, Pola R. Distribution of cerebrovascular phenotypes according to variants of the ENG and ACVRL1 genes in subjects with hereditary hemorrhagic telangiectasia. 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Pediatr Neurol. 2022;129:24\u201330. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2021.12.004.","journal-title":"Pediatr Neurol"}],"container-title":["Italian Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-025-02087-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13052-025-02087-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-025-02087-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:53:41Z","timestamp":1758736421000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijponline.biomedcentral.com\/articles\/10.1186\/s13052-025-02087-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2087"],"URL":"https:\/\/doi.org\/10.1186\/s13052-025-02087-4","relation":{},"ISSN":["1824-7288"],"issn-type":[{"value":"1824-7288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]},"assertion":[{"value":"28 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics approval and consent to participate were obtained (protocol number 6241\/20, ID 2999, date of approval 20 February 2020 by the Ethics Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent to participate and for publication was obtained by all patients or by their parent\/legal guardian.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"268"}}