FBN1related

FBN1-related refers to disorders caused by pathogenic variants in the FBN1 gene, which encodes fibrillin-1, a large glycoprotein that is a major component of microfibrils in the extracellular matrix of connective tissues. The FBN1 gene is located on chromosome 15q21.1. Fibrillin-1 helps form elastic fibers and regulates transforming growth factor beta (TGF-β) signaling. Pathogenic variants lead to connective tissue weakness with variable systemic involvement.

The most well-known FBN1-related condition is Marfan syndrome, a dominantly inherited disorder characterized by cardiovascular, ocular, and skeletal manifestations. Cardiovascular features include progressive dilation of the aortic root and ascending aorta, with risk of dissection. Ocular features often include lens dislocation (ectopia lentis). Skeletal findings commonly include tall stature with long limbs, arachnodactyly, scoliosis, pectus deformities, and joint hypermobility. Onset and severity vary widely, even among affected family members.

Beyond Marfan syndrome, FBN1 variants can give rise to other phenotypes, including isolated ectopia lentis and other forms of thoracic aortic disease without the full Marfan syndrome picture. In general, FBN1-related disorders represent a spectrum of connective tissue phenotypes with overlapping features and variable expressivity.

Inheritance is autosomal dominant, with most cases showing familial transmission but de novo mutations also occur. Diagnosis is based on clinical evaluation supported by molecular testing to identify FBN1 variants. Management emphasizes lifelong surveillance for aortic root size and other complications, medical therapies to slow aortic dilation (such as beta-blockers or ARBs), and timely surgical intervention when indicated. Genetic counseling and family testing are important due to the inherited nature of these conditions.