Overview Marfan's Syndrome is one of the most common inherited disorders of connective tissue. Marfan syndrome is a hereditary disease affecting connective tissues in the body, resulting in symptoms such as aortic dissection and musculoskeletal deformities. However, no family history of Marfan's does not exclude the diagnosis as 30% can occur through gene mutation.
Marfan syndrome: Autosomal dominant disease as a result of mutation in the FBN1 gene. FBN1 gene mutation results in decreased production of fibrillin microfibrils and increased production of TGF- beta, which produces various clinical symptoms and signs.
Fibrillin microfibrils are large glycoproteins that form part of the extracellular matrix. Fibrillin microfibrils endow connective tissues with long-range elasticity
|Antoine Bernard- Jean Marfan (1958-1942) a french paediatrician described a hereditary disorder of connective tissue in a 5 yo girl with disproportionaly long limbs.
Signs and symptoms of Marfan syndrome varies among patients, they are not generally not presented at birth and develops overtime with age. For presentations at birth, it is regarded to as neonatal Marfan syndrome.
|Remember Two cardinal features of Marfan Syndrome is aortic root dilatation and ectopia lentis. This is used in Diagnosis together with family history and confirmed FBN1 mutation
<20 years old
>20 years old
|Ehlers Danlos Syndrome disorder in connective tissue (collagen), characterised by joint hypermobility, elastic skin, skin thinning and bleeding disorders
Ghent Diagnosis (simplified)
Absence of family history
Presence of family history
Fibrillin 1 (FBN1) gene mutation, located on chromosome 15
The fibrillin 1 gene is crucial in the production of fibrillin, a glycoprotein which stabilises crosslinks of microfibril tissues found in connective tissues, such as arteries and skin. Fibrillin either bind microfibril strands to form non-stretchable tissues (such as tendons), or binds microfibril strands with elastin to form elastic fibres (such as arteries). It also sequesters transforming growth factor beta (TGF-B), and promotes connective tissue growth.
With the deformed or deficiency in fibrillin proteins due to the gene mutation, connective tissues loss mechanical integrity.
In the aorta, the lost of integrity in elastic connective tissue causes necrosis of the tunica media, resulting in aortic dilation, which in turns causes aortic valve insufficiency and heart
failure. There is also increased risk of aneurysm formation and dissection of the aorta, causing mortality related to Marfan syndrome.
Marfanoid body habitus, scoliosis, kyphoscoliosis and arthropathy are common symptoms present in Marfan syndrome. Since less fibrillin is present for sequestering the TGF-B, there is a overabundance of such substances in the systemic circulation, therefore other tissues such as epiphyseal plate responds to the constant stimulation of TGF-B, resulting in over-production of long bones.
Increased risk of lens dislocation and retinal detachment due to insufficient connective tissue integrity.
Striae may be seen due to loosening of connective tissues in the dermal layer.
Possible bulla formation in the lungs due to lack of mechanical integrity in lung elastic tissues increases risk of spontaneous pneumothorax.
Treatment of Marfan syndrome is based on symptoms management and improvement of overall life quality of the patient. Each system affected by the FBN1 gene mutation can be