Diagnosis and Management of Marfan Syndrome

Abstract

Marfan syndrome is a disorder of the connective tissue that is inherited in an autosomal-dominant fashion and is caused by mutations in the gene coding for fibrillin-1, FBN1. Although complications of the syndrome may involve the eye, the lung and the skeleton, the high mortality of untreated cases results almost exclusively from cardiovascular complications, including aortic dissection and rupture. Recently, a series of experiments has begun to elucidate the complex molecular etiology of Marfan syndrome, and a number of new heritable syndromes with an associated risk for aortic complications, such as Loeys–Dietz syndrome types I and II, have been described. The multiorgan involvement of many of these syndromes requires multidisciplinary expert centers that can increase the average life expectancy of affected patients from only 32 years to over 60 years. The present article both reviews classical standards of managing cardiovascular manifestations and outlines significant advances in recent research with focus on their impact on future diagnostic and therapeutic options.

Keywords: :

• aorta
• arrhythmia
• cytokines
• fibrillin
• genes
• Loeys–Dietz syndrome
• Marfan syndrome
• matrix metalloproteinases
• sudden death
• TGF-β

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

*Recommended thresholds for timing of prophylactic surgery dropped from 55 mm [28] to 43 mm [49] and 40 mm [50]. For calculation of an aortic ratio, the observed maximum diameter of the aortic root is divided by the predicted diameter based on age and body surface area (BSA) of normal individuals. The predicted sinus diameter (cm), for adults aged 18–40 years equals 0.97 + (1.12 × BSA) (m²) [51].

^‡Recommendations listed here follow the draft of the Professional Advisory Board (PAB) statement of the National Marfan Foundation. Current American Heart Association guidelines recommend prophylaxis of endocarditis only in patients with prosthetic cardiac valves, previous infectious endocarditis or in cardiac transplantation recipients who develop cardiac valvulopathy [52]. The PAB recommends endocarditis prophylaxis also in Marfan patients with dysfunction of their native heart valves. No evidence exists regarding the benefit of endocarditis prophylaxis in patients with Marfan syndrome who have either no valvulopathy or only mitral valve prolapse without regurgitation [Reed Pyeritz & Josephine Grima, Pers. Comm.]. Obtained from [26,29].