Marfan Syndrome

 

Epidemiology and Etiology:

·         1 in 5000

·         Familial in 75-80%

·         AD inheritance

·         Fibrillin-1 defect (FBN1 on 15q21)

·         Extracellular glycoprotein

·         Major component of microfibrils found in the extracellular matrix

·         Microfibrils form a scaffolding on which tropoelastin is deposited to form elastic fibres

·         The abnormal protein is thought to disrupt the assembly of the normal microfibrils (dominant negative mechanism)

·         Variable expressivity reflected in variable clinical expression

·         Note that mutations in its homologue, FBN2 on 5q3 causes a different syndrome, congenital contractural arachnodactyly

 

Common sites:

·         Skeleton

·         ligaments

·         Eyes

·         Ciliary zonules of the lens (supports the lens)

·         Cardiovascular

·         Aorta

·          

 

Gross features:

·         Abraham Lincoln may have had Marfan

·         There is great variation in the clinical expression of this disorder

·         Unusually tall

·         Ratio of upper body (top of the head to pubis) to the lower segment (top of pubic ramus to the floor) is significantly lower than normal for age, race, and gender

·         Exceptionally long extremities

·         Long, tapering fingers and toes

·         Lax joints

·         Hands and feet

·         Thumb can be hyperextended back to the wrist

·         Dolichocephaly (long-headed)

·         Bossing of the frontal eminences

·         Prominent supraorbital ridges

·         Spinal deformities:

·         Kyphosis

·         Scoliosis

·         Rotation or slippage of the dorsal or lumbar vertebrae

·         Chest deformity:

·         Pectus excavatum

·         Pigeon-breast deformity

·         Ocular changes:

·         Bilateral subluxation or dislocation (usually upward and outward) of the lens (ectopia lentis)

·         Suspect Marfan with this finding

·         Cardiovascular:

·         MVP

·         Aortic root dilation

·         Aortic incompetence

·         Aortic aneurysm

·         Aortic dissection (cause of death in 35-45% of Marfan patients)

 

Histologic features:

·         Aorta:

·         Cystic medial degeneration (not specific)

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

·         FBN1 mutations

·         More than 500 distinct mutations have been identified, mostly missense

 

Other features:

·         Cardiac failure (2nd most common cause of death)

 

References:

·         Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.