Marfan Syndrome
• Autosomal Dominant Connective Tissue Disorder
• Fibrillin-1 Abnormality (FBN1)
• Incidence: 1:5000 – 1:10,000
• 25% Cases: Spontaneous Mutation
• 50,000 affected in USA; 200,000 with related connective
tissue disorders
• Multisystem Involvement:
• Cardiovascular, Ocular, Skeletal, Dura

Marfan Syndrome: Clinical Features
Common physical characteristics (outward features)
• Tall, thin stature with disproportionately long arms
• Unusually long lower half of body
• Long, double-jointed fingers, elongated thumb
• Long feet and toes, flat or highly arched feet
• Curvature of the spine (scoliosis)
• Chest wall deformities (pectus excavatum, pectus carinatum)
• Nearsightedness
• Stretch marks (striae atrophicae)

Marfan Syndrome:
Importance of Accurate Diagnosis
• May be diagnosed at birth or not recognized until late in life
• If unrecognized and untreated, the average age of death in Marfan
syndrome is 30 to 40 years.
• Aortic Complications (Aortic Dissection and Aortic Insufficiency)
are responsible for 90% of the Morbidity and Mortality in Marfan
syndrome.
• Careful assessment and long term follow-up are critical to the
outcome of patients with Marfan syndrome.
• Median probability of survival is now into the 70’s.

Molecular Basis of the Marfan Syndrome
• Genetic linkage analysis excluded the collagens as candidate molecules.
• Fibrillin, a 350 kDa glycoprotein component of connective tissue is described
and localized in tissues commonly involved in the Marfan syndrome. (Sakai,
1986)
• Immunohistochemical studies (utilizing antifibrillin antibodies) of cultured
skin fibroblasts suggested decreased fibrillin secretion in the Marfan syndrome.
(Hollister, 1990)
• Family linkage studies map Marfan syndrome to chromosome 15q15-q23 in 5
Finnish families. (Kainulainen 1990, Dietz 1991)
• A probe from the partially cloned fibrillin gene was mapped to the same
region on chromosome 15 (15q15-21) by in situ hybridization.
• DNA polymorphism in the fibrillin gene was tightly linked to the Marfan
syndrome phenotype by family linkage studies (LOD = 7.56). (Lee, 1991)
• Using clones of the fibrillin gene, de novo point mutations were documented
in sporadic cases of Marfan syndrome. (Dietz and Maslen, 1991)
• To date, >100 mutations in fibrillin-1 (FBN-1) have been described in Marfan
syndrome.

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