Schwenter F, Faughnan ME, Gradinger AB, Berk T, Gryfe R, Pollett A et al (2012) Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation. J Gastroenterol.;47(7)

Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD et al (2011) International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet 48(2):73–87

Article  CAS  PubMed  Google Scholar 

Mora-Luján JM, Iriarte A, Alba E, Sánchez-Corral MÁ, Berrozpe A, Cerdà P et al (2020) Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia: risk factors and endoscopic findings. J Clin Med.;9(1)

Serra MM, Papi M, Serrano C (2024) Prevalence of hereditary hemorrhagic telangiectasia in a medical care program organization in Buenos Aires. Argentina Med (B Aires) 84(2):221–226

Google Scholar 

Zarrabeitia R (2016) Epidemiology of Hereditary Haemorrhagic Telangiectasia (HHT) in Spain. Hered Genet 5:1000173

Google Scholar 

Hitchings AE, Lennox PA, Lund VJ, Howard DJ (2005) The effect of treatment for epistaxis secondary to hereditary hemorrhagic telangiectasia. Am J Rhinol 19(1):75–78

Article  PubMed  Google Scholar 

Shovlin C, Gossage J (2016) Pulmonary arteriovenous malformations-evidence of under recognition in respiratory medicine? Eur Respiratory Soc

Shovlin CL (2014) Pulmonary arteriovenous malformations. Am J Respir Crit Care Med 190(11):1217–1228

Article  PubMed  PubMed Central  Google Scholar 

Cottin V, Dupuis-Girod S, Lesca G, Cordier JF (2007) Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler disease). Respiration

Angriman F, Ferreyro BL, Wainstein EJ, Serra MM (2014) Pulmonary arteriovenous malformations and embolic complications in patients with hereditary hemorrhagic telangiectasia. Arch Bronconeumol 50(7):301–304

Article  PubMed  Google Scholar 

Khalid SK, Garcia-Tsao G (2008) Hepatic vascular malformations in hereditary hemorrhagic telangiectasia. Semin Liver Dis 28(3):247–258

Article  PubMed  Google Scholar 

Buscarini E, Manfredi G (2018) Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome) and Liver Vascular Malformations. In: Berzigotti A, Bosch J, editors. Diagnostic Methods for Cirrhosis and Portal Hypertension [Internet]. Cham: Springer International Publishing; pp. 309–24. https://doi.org/10.1007/978-3-319-72628-1_20

Faughnan ME, Mager JJ, Hetts SW, Palda VA, Ratjen F (2021) Second International guidelines for the diagnosis and management of Hereditary Hemorrhagic Telangiectasia. Annals of internal medicine, vol 174. United States, pp 1035–1036

Shovlin CL (2010) Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev 24(6):203–219

Article  CAS  PubMed  Google Scholar 

Tillet E, Bailly S (2014) Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia. Front Genet 5:456

PubMed  Google Scholar 

Ruiz-Llorente L, Gallardo-Vara E, Rossi E, Smadja DM, Botella LM, Bernabeu C (2017) Endoglin and alk1 as therapeutic targets for hereditary hemorrhagic telangiectasia. Expert Opinion on Therapeutic Targets

Abdalla SA, Letarte M (2006) Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. J Med Genet 43(2):97–110

Article  CAS  PubMed  PubMed Central  Google Scholar 

Williams J-CB, Hamilton JK, Shiller M, Fischer L, Deprisco G, Boland CR (2012) Combined juvenile polyposis and hereditary hemorrhagic telangiectasia. Proc (Bayl Univ Med Cent) 25(4):360–364

PubMed  Google Scholar 

Aretz S, Stienen D, Uhlhaas S, Stolte M, Entius MM, Loff S et al (2007) High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet 44(11):702–709

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yehia L, Heald B, Eng C (2023) Clinical spectrum and science behind the Hamartomatous polyposis syndromes. Gastroenterology 164(5):800–811

Article  CAS  PubMed  Google Scholar 

Schwenter F, Ratjen F, Berk T, Gallinger S, Gryfe R, Gradinger AB et al (2012) Juvenile polyposis syndrome, SMAD4 mutations, and hereditary hemorrhagic telangiectasia. J Pediatr Gastroenterol Nutr 54(1):120–122

Article  PubMed  Google Scholar 

Singh AD, Gupta A, Mehta N, Heald B, Macaron C, Liska D et al (2023) Occurrence of gastric cancer in patients with juvenile polyposis syndrome: a systematic review and meta-analysis. Gastrointest Endosc 97(3):407–414e1

Article  PubMed  Google Scholar 

Cao K, Plazzer J-P, Macrae F (2023) SMAD4 variants and its genotype-phenotype correlations to juvenile polyposis syndrome. Hered Cancer Clin Pract 21(1):27

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heald B, Rigelsky C, Moran R, LaGuardia L, O’Malley M, Burke CA et al (2015) Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. Am J Med Genet A 167A(8):1758–1762

Article  PubMed  Google Scholar 

Gheewalla GM, Luther J, Das S, Kreher JB, Scimone ER, Wong AW et al (2022) An additional patient with SMAD4-Juvenile polyposis-Hereditary hemorrhagic telangiectasia and connective tissue abnormalities: SMAD4 loss-of-function and gain-of-function pathogenic variants result in contrasting phenotypes. American journal of medical genetics, vol 188. Part A. United States, pp 3084–3088

O’Malley M, LaGuardia L, Kalady M, Parambil J, Leach B, Eng C et al (2011) The prevalence of hereditary hemorrhagic telangiectasia in Juvenile Polyposis syndrome patients with SMAD4 mutations. 9:O5Hereditary Cancer in Clinical Practice

Guidelines N, Detection, Prevention, Reduction R (2024) https://www.nccn.org/guidelines/category_2

Jelsig AM, Tørring PM, Kjeldsen AD, Qvist N, Bojesen A, Jensen UB et al (2016) JP-HHT phenotype in Danish patients with SMAD4 mutations. Clin Genet 90(1):55–62

Article  CAS  PubMed  Google Scholar 

Caillot C, Saurin J-C, Hervieu V, Faoucher M, Reversat J, Decullier E et al (2024) Phenotypic characterisation of SMAD4 variant carriers. J Med Genet 61(8):734–740

Article  PubMed  Google Scholar 

Jelsig AM, Kjeldsen A, Christensen LL, Bertelsen B, Karstensen JG, Brusgaard K et al (2023) Hereditary haemorrhagic telangiectasia in Danish patients with pathogenic variants in SMAD4: a nationwide study. J Med Genet 60(5):464–468

Article  CAS  PubMed  Google Scholar 

Vázquez C, Gonzalez ML, Ferraris A, Bandi JC, Serra MM (2020) Bevacizumab for treating Hereditary Hemorrhagic Telangiectasia patients with severe hepatic involvement or refractory anemia. PLoS ONE 15(2):e0228486

Article  PubMed  PubMed Central  Google Scholar 

Saurin J-C, Calavas L, Caillot C (2022) Juvenile polyposis: focus on less described manifestations. Best Pract Res Clin Gastroenterol.;58–59:101802

Hosman AE, Devlin HL, Silva BM, Shovlin CL (2013) Specific cancer rates may differ in patients with hereditary haemorrhagic telangiectasia compared to controls. Orphanet J Rare Dis 8:195

Article  PubMed  PubMed Central  Google Scholar 

Hosman AE, Shovlin CL (2017) Cancer and hereditary haemorrhagic telangiectasia. Vol. 143, Journal of cancer research and clinical oncology. Germany; pp. 369–70

Duarte CW, Black AW, Lucas FL, Vary CPH (2017) Cancer incidence in patients with hereditary hemorrhagic telangiectasia. J Cancer Res Clin Oncol 143(2):209–214

Article  CAS  PubMed  Google Scholar 

Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA et al (2022) Diagnosis and management of Cancer Risk in the gastrointestinal hamartomatous polyposis syndromes: recommendations from the US Multi-society Task Force on Colorectal Cancer. Gastroenterology 162(7):2063–2085

Article  CAS  PubMed  Google Scholar 

Bosman FT (1999) The hamartoma-adenoma-carcinoma sequence. The Journal of pathology, vol 188. England, pp 1–2

Perzin KH, Bridge MF (1982) Adenomatous and carcinomatous changes in hamartomatous polyps of the small intestine (Peutz-Jeghers syndrome): report of a case and review of the literature. Cancer 49(5):971–983

Article  CAS  PubMed  Google Scholar 

Gupta S, Provenzale D, Regenbogen SE, Hampel H, Slavin TP, Hall MJ et al (2017) NCCN guidelines insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017. J Natl Compr Canc Netw 15(12):1465–1475

Article  CAS  PubMed  Google Scholar 

McDonald NM, Ramos GP, Sweetser S (2020) SMAD4 mutation and the combined juvenile polyposis and hereditary hemorrhage telangiectasia syndrome: a single center experience. Int J Colorectal Dis 35(10):1963–1965

Article  PubMed  Google Scholar 

Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S et al (2004) A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet

Wain KE, Ellingson MS, McDonald J, Gammon A, Roberts M, Pichurin P et al (2014) Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review. Genet Med off J Am Coll Med Genet 16(8):588–593

CAS  Google Scholar 

Vorselaars VMM, Diederik A, Prabhudesai V, Velthuis S, Vos J-A, Snijder RJ et al (2017) SMAD4 gene mutation increases the risk of aortic dilation in patients with hereditary haemorrhagic telangiectasia. Int J Cardiol 245:114–118

Article  CAS  PubMed  Google Scholar 

Zhang P, Hou S, Chen J, Zhang J, Lin F, Ju R et al (2016) Smad4 Deficiency in smooth muscle cells initiates the formation of aortic aneurysm. Circ Res 118(3):388–399

Article  CAS  PubMed  Google Scholar 

Teekakirikul P, Milewicz DM, Miller DT, Lacro RV, Regalado ES, Rosales AM et al (2013) Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations. Am J Med Genet A 161A(1):185–191