What genetic defect is associated with Marfan syndrome?

From the Guidelines

Marfan syndrome is associated with a genetic defect in the FBN1 gene, which encodes the protein fibrillin-1, as confirmed by the most recent study 1. This mutation affects the formation of elastic fibers in connective tissue throughout the body. Fibrillin-1 is a critical component of microfibrils, which provide structural support to tissues and help regulate growth factors. When this protein is defective, it leads to the characteristic features of Marfan syndrome, including tall stature, long limbs, cardiovascular problems (particularly aortic enlargement and mitral valve prolapse), ocular issues like lens dislocation, and skeletal abnormalities. The condition follows an autosomal dominant inheritance pattern, meaning a person needs only one copy of the mutated gene to develop the syndrome. About 75% of cases are inherited from a parent, while the remaining 25% result from new mutations, as noted in 1. Some key points to consider in the management of Marfan syndrome include:

• The importance of regular imaging surveillance of the aorta, typically performed annually, with the frequency dependent on age, aortic diameter, rate of aortic growth, and family history 1.
• The use of beta blockers or angiotensin receptor blockers (ARBs) to slow the growth of the aortic root and prevent aortic dissection, with studies showing a mean growth of the aortic root of 1 mm to 1.5 mm over 3 years and 4 mm to 5 mm over 5 years 1.
• The consideration of prophylactic aortic root replacement for aneurysm disease to prevent type A dissection and improve survival in Marfan syndrome, as recommended in 1.

From the Research

Genetic Defect Associated with Marfan Syndrome

The genetic defect associated with Marfan syndrome is a mutation in the FBN1 gene, which encodes the protein Fibrillin 1 [ 2, 3, 4, 5, 6 ]. This mutation affects the function of Fibrillin 1, a structural molecule that forms microfibrils in connective tissue.

Types of FBN1 Mutations

There are several types of FBN1 mutations associated with Marfan syndrome, including:

• Missense mutations [ 3 ]
• Splicing mutations [ 3 ]
• Frameshift mutations [ 3 ]
• Nonsense mutations [ 3 ]

Effects of FBN1 Mutations

FBN1 mutations can lead to a range of clinical features, including:

• Tall stature and arachnodactyly [ 4, 6 ]
• Ectopia lentis (congenital dislocation of the lens) [ 4 ]
• Thoracic aortic aneurysm and dissection [ 2, 3, 4 ]
• Cardiovascular complications, including cardiomyopathy and arrhythmia [ 4 ]
• Musculoskeletal abnormalities, including kyphosis and scoliosis [ 4, 5 ]