{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:04:03Z","timestamp":1790708643664,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myhre syndrome is a rare autosomal\u2010dominant disorder caused by gain\u2010of\u2010function pathogenic variants in\n                    <jats:italic>SMAD4<\/jats:italic>\n                    and is now recognized as a progressive multisystem fibrotic disease. Although transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signaling plays a central role in hepatic fibrogenesis, hepatobiliary involvement in Myhre syndrome has not been systematically evaluated. We report the first case of Myhre syndrome complicated by rapidly progressive biliary cirrhosis requiring liver transplantation in a 15\u2010year\u2010old male with a confirmed\n                    <jats:italic>SMAD4<\/jats:italic>\n                    p.Ile500Val variant. Following an infectious episode, the patient developed severe cholestasis with imaging and histopathologic findings consistent with fibro\u2010obliterative cholangiopathy, ultimately necessitating living donor liver transplantation. A systematic review of 55 published reports comprising 217 patients with Myhre syndrome revealed that hepatic evaluation was rarely performed and that previously reported liver abnormalities were mild and secondary, most commonly related to right heart dysfunction or metabolic disease, with no prior cases of progressive biliary fibrosis. This case suggests that dysregulated\n                    <jats:italic>SMAD4<\/jats:italic>\n                    \u2013TGF\u2010\u03b2 signaling may predispose selected organs to fibro\u2010obliterative injury and that infection\u2010driven inflammation may act as a critical trigger for hepatic fibrosis in Myhre syndrome, expanding the recognized spectrum of organ involvement in this disorder.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70201","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:01:21Z","timestamp":1778814081000},"page":"2250-2259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biliary Cirrhosis in Myhre Syndrome: The First Case Report of Liver Transplantation and a Review of Reported Hepatic Findings"],"prefix":"10.1002","volume":"200","author":[{"given":"Yiyoung","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Pediatrics, 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