Marfan Syndrome: Enhanced Diagnostic Tools and Follow-up Management Strategies

Abstract

Marfan syndrome (MFS) is a rare inherited autosomic disorder, which encompasses a variety of systemic manifestations caused by mutations in the Fibrillin-1 encoding gene (FBN1). Cardinal clinical phenotypes of MFS are highly variable in terms of severity, and commonly involve cardiovascular, ocular, and musculoskeletal systems with a wide range of manifestations, such as ascending aorta aneurysms and dissection, mitral valve prolapse, ectopia lentis and long bone overgrowth, respectively. Of note, an accurate and prompt diagnosis is pivotal in order to provide the best treatment to the patients as early as possible. To date, the diagnosis of the syndrome has relied upon a systemic score calculation as well as DNA mutation identification. The aim of this review is to summarize the latest MFS evidence regarding the definition, differences and similarities with other connective tissue pathologies with severe systemic phenotypes (e.g., Autosomal dominant Weill–Marchesani syndrome, Loeys–Dietz syndrome, Ehlers–Danlos syndrome) and clinical assessment. In this regard, the management of MFS requires a multidisciplinary team in order to accurately control the evolution of the most severe and potentially life-threatening complications. Based on recent findings in the literature and our clinical experience, we propose a multidisciplinary approach involving specialists in different clinical fields (i.e., cardiologists, surgeons, ophthalmologists, orthopedics, pneumologists, neurologists, endocrinologists, geneticists, and psychologists) to comprehensively characterize, treat, and manage MFS patients with a personalized medicine approach.

Marfanoid to Mortality: A Case Report on Sudden Cardiac Death Due to Aortic Dissection in a Young Male With Marfanoid Habitus

“…Marfanoid habitus, an autosomal dominant connective tissue disorder, resembles MFS and is characterized by a tall and slender physique, dolichostenomelia, arm span larger than height, arachnodactyly of hands and feet, little subcutaneous fat, and muscle hypotonia with a positive thumb and wrist sign, as observed in this case [ 7 ]. These also serve as a red flag clinical marker prompting further investigation due to the association between MFS and cardiovascular complications.…”

Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease

“…While longitudinal studies of human mitral valve prolapse progression support a similar progression toward significant mitral regurgitation over years with changes in mitral leaflet morphology, 55 regular monitoring of apparently healthy individuals will be needed for early detection of MVD. 56 Moreover, efforts toward inhibiting Wnt signaling clinically for a variety of conditions have not been successful, largely due to the requirement for this pathway in healthy gut function. 57 Thus, the precise modulation of Wnt signaling levels and organ-specific targeting must be carefully considered to reach the desired therapeutic outcome and avoid adverse side effects.…”