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A retrospective multi-centre case-note review identified 28 patients with a pathogenic <jats:italic>SMAD4<\/jats:italic> variant from 13 families across all Scottish Clinical Genetics Centres. This provided a complete clinical picture of the Scottish JP-HHT cohort. Colonic polyps were identified in 87% (23\/28) and gastric polyps in 67% (12\/18) of screened patients. Complication rates were high: 43% (10\/23) of patients with polyps required a colectomy and 42% (5\/12) required a gastrectomy. Colorectal cancer occurred in 25% (7\/28) of patients, at a median age of 33 years. Pulmonary arteriovenous malformations were identified in 42% (8\/19) of screened patients. 88% (23\/26) and 81% (17\/21) of patients exhibited JP and HHT features respectively, with 70% (14\/20) demonstrating features of both conditions. We have shown that individuals with a pathogenic <jats:italic>SMAD4<\/jats:italic> variant are all at high risk of both gastrointestinal neoplasia and HHT-related vascular complications, requiring a comprehensive screening programme.<\/jats:p>","DOI":"10.1038\/s41431-024-01607-w","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T09:04:10Z","timestamp":1713258250000},"page":"731-735","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Outcomes of patients with Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia caused by pathogenic SMAD4 variants in a pan-Scotland cohort"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9104-9189","authenticated-orcid":false,"given":"Madeline","family":"Pearson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"McGowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2418-0390","authenticated-orcid":false,"given":"Philip","family":"Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-7469","authenticated-orcid":false,"given":"Wayne","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-8136","authenticated-orcid":false,"given":"Zofia","family":"Miedzybrodzka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4459-4830","authenticated-orcid":false,"given":"Jonathan","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"1607_CR1","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1016\/S0016-5085(19)30517-7","volume":"78","author":"KL Cox","year":"1980","unstructured":"Cox KL, Frates RC Jr., Wong A, Gandhi G. 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