{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:16:26Z","timestamp":1788498986709,"version":"build-2803163510"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      FBN1-related geleophysic dysplasia (GD2) is an ultrarare autosomal dominant disorder caused by dominant-negative missense variants in the TGF\u03b2-binding protein-like domain 5 (TB5) of\n                      <jats:italic>FBN1<\/jats:italic>\n                      . It is characterized by severe short stature, brachydactyly, progressive joint stiffness, and cardiac valvular disease. Although hepatomegaly is known to occur in GD, progression to cirrhosis with portal hypertension in the elderly has never been documented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 76-year-old Chinese man presented with a 1-year history of abdominal distension and was found to have liver cirrhosis during routine examination. He had no history of viral hepatitis, alcohol abuse, or other conventional liver disease risk factors. Physical examination revealed short stature (128\u00a0cm), brachydactyly, and mild scleral icterus. His 39-year-old daughter shared a similar skeletal phenotype and had a history of cardiac valve replacement. Laboratory tests showed moderate hyperbilirubinemia and mild thrombocytopenia with normal liver enzymes. Serological screening markers for viral hepatitis and autoimmune liver disease were all unremarkable. Liver elastography (15.5 kPa) and contrast-enhanced MRI confirmed cirrhosis with portal hypertension. Whole-genome sequencing identified a heterozygous pathogenic\n                      <jats:italic>FBN1<\/jats:italic>\n                      variant (c.5284G&amp;gt;A, p.Gly1762Ser) in both the proband and his daughter, confirming a diagnosis of GD. The patient was managed supportively and remained stable over 6 months of follow-up.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      To our knowledge, this is the first reported case of late-onset liver cirrhosis in an elderly GD patient caused by an\n                      <jats:italic>FBN1<\/jats:italic>\n                      variant. This case raises the possibility that hepatic manifestations related to GD could be linked to late-onset cirrhosis, though a causal or progressive relationship cannot be confirmed due to absent serial hepatic assessments prior to cirrhosis diagnosis. For elderly patients with unexplained late-onset liver cirrhosis combined with short stature or multisystem malformations,\n                      <jats:italic>FBN1<\/jats:italic>\n                      genetic testing may be considered. In addition, long-term hepatic monitoring may be considered for middle-aged and elderly patients or those with TB5 domain variants, although universal surveillance for all affected individuals is not supported by the current evidence.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1822591","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:27:10Z","timestamp":1788496030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Late-onset liver cirrhosis in an elderly patient with FBN1-related Geleophysic Dysplasia"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuqi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.1.34","article-title":"In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome","volume":"40","author":"Faivre","year":"2003","journal-title":"J Med Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31337","article-title":"From tall to short: the role of TGFbeta signaling in growth and its disorders","author":"Le Goff","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ajhg.2011.05.012","article-title":"Mutations in the TGFbeta binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias","volume":"89","author":"Le Goff","year":"2011","journal-title":"Am J Hum Genet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048634","article-title":"Fibrillin-1 mutations causing Weill-Marchesani syndrome and acromicric and geleophysic dysplasias disrupt heparan sulfate interactions","volume":"7","author":"Cain","year":"2012","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.07.033","article-title":"FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders","volume":"591","author":"Sakai","year":"2016","journal-title":"Gene"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.844","article-title":"Skin fibroblasts of patients with geleophysic dysplasia due to FBN1 mutations have lysosomal inclusions and losartan improves their microfibril deposition defect","volume":"7","author":"Piccolo","year":"2019","journal-title":"Mol Genet Genomic Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00994-x","article-title":"Geleophysic and acromicric dysplasias: natural history, genotype-phenotype correlations, and management guidelines from 38 cases","volume":"23","author":"Marzin","year":"2021","journal-title":"Genet Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.11.018","article-title":"A report of three families with FBN1-related acromelic dysplasias and review of literature for genotype-phenotype correlation in geleophysic dysplasia","volume":"61","author":"Cheng","year":"2018","journal-title":"Eur J Med Genet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8212417","article-title":"The clinical cases of geleophysic dysplasia: One gene, different phenotypes","volume":"2018","author":"Globa","year":"2018","journal-title":"Case Rep Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087544","article-title":"Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia","volume":"48","author":"Allali","year":"2011","journal-title":"J Med Genet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(71)92073-3","article-title":"Geleophysic dwarfism--a \"focal\" mucopolysaccharidosis","volume":"2","author":"Spranger","year":"1971","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8628(19960503)63:1<50::aid-ajmg11>3.0.co;2-t","article-title":"Clinical and ultrastructural findings in three patients with geleophysic dysplasia","volume":"63","author":"Pontz","year":"1996","journal-title":"Am J Med Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30450","article-title":"Natural history of cardiac involvement in geleophysic dysplasia","author":"Scott","year":"2005","journal-title":"Am J Med Genet A"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2025.1642390","article-title":"Case report: A case of severe pulmonary hypertension combined with FBN1 mutation associated geleophysic dysplasia","volume":"13","author":"Chen","year":"2025","journal-title":"Front Pediatr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1246-y","article-title":"TGF-beta in progression of liver disease","volume":"347","author":"Dooley","year":"2012","journal-title":"Cell Tissue Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00845.x","article-title":"Utility of molecular analyses in the exploration of extreme intrafamilial variability in the Marfan syndrome","volume":"72","author":"De Backer","year":"2007","journal-title":"Clin Genet"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1822591\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:27:11Z","timestamp":1788496031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1822591\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":16,"alternative-id":["10.3389\/fendo.2026.1822591"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1822591","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]},"article-number":"1822591"}}