Cureus. 2026 Aug 31;18(8):e115500. doi: 10.7759/cureus.115500. eCollection 2026 Aug.
ABSTRACT
Marfan syndrome (MFS) is an autosomal dominant multisystemic connective tissue disorder caused by pathogenic variants in the FBN1 gene and characterized by cardiovascular, ocular, and musculoskeletal manifestations. Ocular findings commonly include strabismus, refractive error, ectopia lentis, glaucoma, and retinal detachment. We report the case of a 14-year-old male patient with a variant of uncertain significance (VUS) in the FBN1 gene and a phenotype compatible with the Marfan spectrum. Clinical data were obtained from ophthalmic examination, ocular imaging, echocardiographic findings, and next-generation sequencing. The patient underwent ophthalmic evaluation as part of the workup for suspected MFS and had a best-corrected visual acuity of 20/30-1 and 20/30+1 in the right and left eyes, respectively. Slit-lamp examination showed minimal bilateral inferior lens subluxation (ectopia lentis) upon downgaze, and fundus examination showed bilateral optic disc cupping with otherwise normal posterior segment findings. Optical coherence tomography showed symmetric retinal nerve fiber layer thickness and a mild inter-eye difference in the cup-to-disc ratio. Based on bilateral optic disc cupping, the patient was considered a glaucoma suspect; however, glaucoma was not established. Systemic findings resulted in a Ghent systemic score of 7, while cardiovascular evaluation showed no evidence of aortic root dilation. Next-generation sequencing using an aortopathy panel identified a heterozygous FBN1 c.7004G>A (p.Arg2335Gln) variant classified as a VUS. This case highlights the diagnostic challenges of interpreting FBN1 variants of uncertain significance in patients with a highly suggestive Marfan spectrum phenotype and underscores the importance of comprehensive phenotypic assessment for clinical diagnosis and long-term management. The identified VUS cannot establish disease causality or provide definitive molecular confirmation. Rather, this case contributes phenotypic information regarding an unresolved FBN1 variant that may inform future genotype-phenotype correlation and variant re-evaluation as additional evidence becomes available.
PMID:42820018 | PMC:PMC13625754 | DOI:10.7759/cureus.115500