Abstract
Background
FBN1-related geleophysic dysplasia (GD2) is an ultrarare autosomal dominant disorder caused by dominant-negative missense variants in the TGFβ-binding protein-like domain 5 (TB5) of
FBN1
. 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.
Case presentation
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 cm), 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
FBN1
variant (c.5284G>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.
Conclusion
To our knowledge, this is the first reported case of late-onset liver cirrhosis in an elderly GD patient caused by an
FBN1
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,
FBN1
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.