From the Guidelines
Marfan syndrome is inherited in an autosomal dominant manner.
Key Features of Marfan Syndrome
- The syndrome is caused by mutations in the FBN1 gene, which encodes fibrillin-1, a glycoprotein that is secreted from cells and deposited in the extracellular matrix [ 1 ].
- Approximately 25% of patients do not have a family history and represent new cases due to sporadic mutations for the condition [ 1 ].
- The FBN1 gene mutations lead to a deficiency of fibrillin, which may cause weakening of the supportive tissues and dysregulation of transforming growth factor-b (TGF-b) [ 1 ].
- More than 1000 mutations have been identified in the FBN1 gene, almost all unique to an affected family [ 1 ].
- The syndrome has a high penetrance but variable expression, with cardinal features involving the cardiovascular, ocular, and skeletal systems [ 1 ].
Inheritance Pattern
- Marfan syndrome is inherited in an autosomal dominant manner, meaning that an individual with the syndrome has a 50% risk of passing it on to their children [ 1 ].
- Family members of an individual with Marfan syndrome should be evaluated for possible predisposition to thoracic aortic aneurysm and dissections, with imaging recommended every 2 years [ 1 ].
- The variable age of onset of aortic disease in familial thoracic aortic aneurysms and dissections highlights the importance of regular monitoring and evaluation [ 1 ].
From the Research
Inheritance of Marfan Syndrome
- Marfan syndrome is an inherited, autosomal dominant disorder that affects the skeletal, ocular, and cardiovascular systems 2, 3, 4, 5.
- The disorder is caused by mutations in the gene for fibrillin-1 (FBN1) located on chromosome 15q21.1 2, 3, 6, 4, 5.
- The mutations in the FBN1 gene lead to defects in the connective tissue protein fibrillin, which is a component of microfibrils found in the extracellular matrices of most tissues 2, 3, 4.
- Genetic linkage between the fibrillin gene and the Marfan phenotype has been established, and the gene has been mapped to the same chromosomal position as the disease locus 2.
- In some cases, Marfan syndrome can be caused by a reciprocal chromosomal translocation involving the FBN1 gene, leading to its disruption 6.
- The disorder can be inherited from a parent or can result from a de novo mutation in the FBN1 gene 3, 4.