Treatment of aortic disease in patients with Marfan syndrome.

Marfan syndrome (MFS) is a heritable disorder of the connective tissue with a prevalence of 1 in 3000 to 5000 individuals. The condition is inherited in an autosomal dominant manner with complete penetrance but demonstrates variable expression with significant intraand interfamilial variation. Approximately 25% of patients do not have a family history and represent sporadic, new mutations for the condition. The cardinal features of MFS involve the cardiovascular, ocular, and skeletal systems. The most lifethreatening complication of MFS is thoracic aortic aneurysms leading to aortic dissection, rupture, or both. This article focuses on medical and surgical treatment of aortic disease in patients with MFS and addresses the treatment of aortic disease in children and pregnant women with the condition. The most common cardiovascular complication in patients with MFS is progressive aortic root enlargement initially occurring at the sinuses of Valsalva. Ascending aortic aneurysm can precipitate acute type A aortic dissection, aortic rupture, aortic regurgitation (AR), or all 3, and these complications were the primary cause of death before the advent of successful preventive therapies. Treatment of the aorta consists of regular imaging to detect and quantify progression of aortic dilation, -adrenergic receptor antagonist therapy, and prophylactic aortic repair when the dilation reaches a sufficient size to threaten dissection or cause AR. Before the era of open-heart surgery, the majority of patients with MFS died prematurely of rupture of the aorta, with an average life expectancy of 45 years.1 The success of current medical and surgical treatment of aortic disease in MFS has substantially improved the average life expectancy, extending it up to 70 years.2,3 Cardiovascular manifestations in MFS also include valvular disease involving the mitral valve, aortic valve, or both. Mitral valve prolapse is the most prevalent valvular abnormality, affecting 35% to 100% of patients.4 Mitral regurgitation is more common in children and women with MFS. It is also important to note that if severe mitral regurgitation prompts surgical repair of the mitral valve, the ascending aorta should be observed carefully postoperatively because hemodynamic stresses on the aorta increase. AR can result from distortion of the aortic valve cusps by the enlarged aortic root and occurs in 15% to 44% of patients. Other complications of MFS involve the eye, skeletal system, and integument. The lens of the eye is dislocated in 50% of people with MFS (ectopia lentis) and often is so subtle that it is apparent only with full dilation of the pupil. Myopia is common in MFS, but retinal detachment is a rare complication that may be more common if the lenses are surgically removed. The skeletal features of the disorder include increased height and arm span; anterior chest wall deformities (pectus excavatum or carinatum); long fingers (arachnodactyly) and toes; mild to moderate joint laxity; a narrow, highly arched palate; pes planus; protrusio acetabulum; and vertebral column abnormalities (scoliosis and thoracic lordosis). Dural ectasia (widening of the dural sac, leading to back pain and headache) occurs in 60% of patients with MFS.5 Spontaneous pneumothoraces, recurrent hernias, and striae atrophicae also are features of the condition. MFS results from mutations in the FBN1 gene, which encodes a large glycoprotein of 350 kDa termed