ASARE SMART

TOPIC; MARFAN SYNDROME.

INTRODUCTION.• Marfan syndrome is a disorder of the

connective tissues of the body, manifested principally by changes in the skeleton, eyes, and cardiovascular system." Its prevalence is estimated to be 1 in 5000. Approximately 70% to 85% of cases are familial and transmitted by autosomal dominant inheritance. The remainder are sporadic and arise from new mutations.

Pathogenesis• Marfan syndrome results from an inherited

defect in an extracellular glycoprotein called f ibrillin-1. Fibrillin is the major component of microfibrils found in the extracellular matrix. These fibrils form a scaffolding on which tropo-elastin is deposited to form elastic fibers. Although microfibrils are widely distributed in the body, they are particularly abundant in the aorta, ligaments, and ciliary zonules of the lens, where they support the lens; these tissues are prominently affected in Marfan syndrome.

Pathogenesis cont.• Fibrillin occurs in two homologous forms,

fibrillin-1 and fibrillin-2, encoded by two separate genes, FBNI and FBN2, mapped to chromosomes 15q21.1 and 5q3, respectively. Mutations of FBN1 underlie Marfan syndrome.

Mutations of the related FBN2 gene are less common, and they give rise to congenital contractural arachnodactyly, an autosomal dominant disorder characterized by skeletal abnormalities (Robbins, 2013)

Morphology• Skeletal abnormalities are the most striking feature of

Marfan syndrome. Typically the patient is unusually tall with exceptionally long extremities and long, tapering fingers and toes.

• Because the lower segment of the body largely contributes the tall stature, the ratio of the upper segment (top of the head to the pubis) to the lower segment (top of pubic ramus to the floor) is significantly lower than the norm for age, race, and gender. The joint ligaments in the hands and feet are lax, suggesting that the patient is double-jointed; typically the thumb can be hyperextended back to the wrist. The head is commonly dolichocephalic (long-headed) with bossing of the frontal eminences and prominent supraorbital ridges.

FACTS• The chest is classically deformed, presenting either

pectus excavatum (deeply depressed sternum)• or a pigeon-breast deformity. The ocular changes

take many forms. Most characteristic• is bilateral subluxation or dislocation (usually

outward and upward) of the lens, referred to as• ectopia lentis. This abnormality is so uncommon in

persons who do not have this genetic disease that the

• finding of bilateral ectopia lentis should raise the suspicion of Marfan syndrome.

CLINICAL FEATURES• Cardiovascular lesions are the most life-threatening

features of this disorder. Loss of medial support results in progressive dilation of the aortic valve ring and the root of the aorta, giving rise to severe aortic incompetence.

• In addition, loss of fibrillin-1 from the adventitia also likely contributes to aortic dilation. Although mitral valve lesions are more frequent, they are clinically less important than aortic lesions. Loss of connective tissue support in the mitral valve leaflets makes them soft and billowy, creating the so called floppy valve. Valvular lesions, along with lengthening of the chordae tendineae, frequently give rise to mitral regurgitation.

Diagnosis• Echocardiography greatly enhances the ability

to detect the cardiovascular abnormalities and is therefore extremely valuable in the diagnosis of Marfan syndrome. The great majority of deaths are caused by rupture of aortic dissections, followed in importance by cardiac failure.

REFERENCES• Kumar, Vinay. Abbas k, Abul. Fausto, Nelson. & Aster C, Jon.

(2013). Pathologic Basis of Disease. Page 154-155. Publisher; Saunders Publishers, Philadelphia, Pennsylvania 19103-2899.