Fibrillinopathies

Fibrillinopathies are a group of genetic disorders characterized by abnormalities in fibrillin, a glycoprotein essential for the structural integrity of connective tissues. These conditions primarily affect the extracellular matrix, leading to systemic connective tissue dysfunction. The most well-known fibrillinopathy is Marfan syndrome, but other related disorders include Shprintzen-Goldberg syndrome and congenital contractural arachnodactyly (Beals syndrome).

Fibrillin is a major component of microfibrils, which provide scaffolding for elastin fibers in connective tissues. Mutations in the *FBN1* gene, which encodes fibrillin-1, disrupt normal microfibril formation, resulting in weakened and fragile connective tissues. Symptoms vary depending on the specific mutation and affected tissues but often include skeletal, ocular, and cardiovascular manifestations. Common features may include tall stature, long limbs, joint hypermobility, lens dislocation, and aortic root dilation or dissection.

Diagnosis typically involves clinical evaluation, genetic testing, and imaging studies such as echocardiograms or MRI scans. Treatment focuses on managing symptoms and complications, particularly cardiovascular risks, through medications like beta-blockers or surgical interventions like aortic root replacement. Genetic counseling is recommended for affected individuals and their families due to the hereditary nature of these disorders.

Fibrillinopathies are inherited in an autosomal dominant pattern, meaning an affected individual has a 50% chance of passing the mutation to each child. While there is no cure, early diagnosis and proactive management can significantly improve quality of life and longevity. Research continues to advance understanding of fibrillinopathies, potentially leading to new therapeutic approaches.