Intrafamilial heterogeneity of clinical manifestations of a FBN1 gene variant in Marfan syndrome
TL;DR
This case demonstrates that a causative variant does not allow for a definitive prognosis of the disease course, and all carriers of the identified variant require regular multidisciplinary monitoring, regardless of the severity of clinical manifestations at the time of diagnosis.
Abstract
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.