Intrafamilial heterogeneity of clinical manifestations of a FBN1 gene variant in Marfan syndrome

Marfan syndrome is an autosomal dominant hereditary disorder of connective tissue characterized by pronounced phenotypic variability. The presented case describes a family with clinical manifestations ranging from isolated ectopia lentis to severe aortic disease without a characteristic phenotype. Furthermore, the age of onset and rate of progression of cardiovascular disease in the relatives also varied significantly. Genetic testing identified a missense variant in exon 10 of the FBN1 gene, resulting in a substitution of a cysteine residue in the TB1 domain of fibrillin-1, which was considered likely pathogenic. Verification of the diagnosis of Marfan syndrome allowed for timely referral of the proband to a cardiovascular surgeon to determine further treatment and adjust therapy. This case also demonstrates that a causative variant does not allow for a definitive prognosis of the disease course. Therefore, all carriers of the identified variant require regular multidisciplinary monitoring, regardless of the severity of clinical manifestations at the time of diagnosis.