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Marfan syndrome is a multisystem connective tissue disease caused by a defect in the protein fibrillin 1, encoded by the FBN1 gene. Cardiovascular involvement with aortic root dilatation and dissection is the most feared complication of the disease.
The estimated prevalence is around 2-6 per 100,000 2,5. There is no recognized gender or racial predilection.
Patients with Marfan syndrome may have the following symptoms and signs:
- tall stature
- long arm span (often exceeding the height of the patient)
- joint laxity resulting in recurrent dislocations
- pelvis / lower limbs
- chest wall deformities (present in up to ⅔ of cases 2)
The Ghent Nosology was established in 1995 for the clinical diagnosis of the disease 7.
The condition results from a mutation in the fibrillin 1 (FBN1) gene located on chromosome 15q21.1 which is responsible for cross-linking collagen. In the majority of cases it is inherited in an autosomal dominant fashion, although in up to one-third of cases the mutation is de novo. The disease has high genetic penetrance but with variable phenotypic expression even amongst affected family members.
Studies show a regulatory relationship between extracellular microfibrils and TGFβ signaling, so an abnormality in either can cause a Marfanoid phenotype 9.
Microscopically the arterial walls may show cystic medial necrosis 10.
There are no specific radiographic features of Marfan syndrome but the following signs and complications of the disease may be seen in each system on a range of modalities:
- osteopenia 1
- joint dislocation
- pelvis / lower limbs
- chest wall deformities
- aortic root dilatation and myxomatous degeneration of the mitral valve resulting in mitral valve regurgitation are the most two common cardiac manifestations 9
aortic aneurysm and aortic dissection are the most fearsome consequences - findings suggestive of higher risk of aortic dissection are:
- family history of aortic dissection
- dilatation at the aortic sinotubular junction
- aortic root diameter >55 mm
- increased aortic stiffness
- excessive aortic root dilatation (>1.7 mm/year)
- arterial dissection
- aortic valve regurgitation (AR)
- aortic coarctation
- pulmonary arterial dilatation
Treatment and prognosis
Beta blockers are shown to reduce the rate of aortic root dilatation. In patients who can not take beta-blockers, calcium-channel blockers are used. More recently, investigators found that angiotensin receptor blockers which are also TGFβ antagonists significantly reduce cardiovascular and other somatic features 9. Cardiovascular complications are the most frequent cause of death 2.
Some of the more newer treatment options include.
History and etymology
First described in 1896 by Antoine Bernard-Jean Marfan, French pediatrician (1858-1942).
- congenital contractural arachnodactyly: has significant phenotypic overlap with Marfan syndrome, but is now considered a discrete entity, due to distinct genetics 11
- Loeys-Dietz syndrome: similar features to Marfan syndrome
- homocystinuria: may resemble those with Marfan syndrome in some aspects 8; ectopia lentis, however, is downward as opposed to Marfan and intellectual disability is also a common feature
- multiple endocrine neoplasia type IIb may have a Marfan syndrome like body habitus
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