Marfan Syndrome

Clinical Features, Genes and Therapeutics

Clinical features of PXE
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Marfan syndrome is a hereditary disorder of connective tissue which primarily affects the cardiovascular, skeletal, and ocular systems; more specifically, the skeleton, lungs, eyes, heart and blood vessels. It is an autosomal dominant disorder Opens in new window stemming from defects in the FBN1 gene that encodes fibrillin-1. Fibrillin is a large glycoprotein that is a calcium-binding component of certain connective tissue microfibrils.

In 25% of people, Marfan syndrome develops due to spontaneous mutation; patients rarely survive beyond the fifth decade of life. Prevalence of Marfan syndrome is at least 1 per 5,000 in the general population. It is estimated that 200,000 people in the USA have the syndrome or a related connective tissue disorder.

clinical manifestations of Marfan syndrome

Skeletal manifestations of Marfan syndrome include a dolichocephalic skull; large paranasal sinuses; high, arched palate; pectus excavatum; kyphoscoliosis; long extremities; arachnodactyly; flat feet; hyperextensible or loose jointedness and disproportionate growth that usually results in tall stature.

The cardiovascular manifestations include aneurismal dilatation of the ascending aorta, mitral prolapsed, and aortic and mitral valve incompetence.

The subcutaneous fat is sparse; striae are commonly seen; serpiginous perforating elastosis is occasionally found.

The ocular features of Marfan syndrome include superotemporal subluxated lenses, diffuse and focal iris transillumination defects, glaucoma, myopia, and retinal detachment.

Heterochromia iridis and blue sclera have been uncommonly reported. About 50% of patients with Marfan syndrome have dislocation of the ocular lens. Individuals with Marfan syndrome are often near sighted (myopic).

The major risks to an individual with Marfan syndrome are cardiovascular problems arising from the two primary defects: aortic root dilation and mitral valve prolapse.

The aorta is generally wider and more fragile in patients with Marfan syndrome. This widening is progressive and can cause leakage of the aortic valve or tears (dissection) in the aorta wall.

When the aorta becomes greatly widened, surgical repair is necessary. The risk of sudden death increases as aortic root diameter increases. Treatment with beta-blockers limits the progression of aortic dilation. Various surgical techniques are possible.

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