Marfan Syndrome—Diagnosis and Management

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Abstract

Marfan syndrome (MFS) is the most common inherited disorder of connective tissue that affects multiple organ systems. This autosomal-dominant condition has an incidence of 2-3 per 10,000 individuals. Although genetic testing is available, the diagnosis is still primarily made using the Ghent criteria. Early identification and appropriate management is critical for patients with MFS who are prone to the life-threatening cardiovascular complications of aortic dissection and rupture. Advances in the understanding of the cause of MFS, early recognition of the disorder, and subsequent institution of medical and surgical therapy has resulted in dramatic improvement in the prognosis of this patient population over the past few decades. Beta-blockers have been demonstrated to slow aortic growth and thus delay the time to aortic surgery. Operative intervention has markedly changed the prognosis of patients with MFS and can be safely performed on an elective basis. Identification of presymptomatic patients is critical to reduce the frequency of catastrophic aortic events.

Section snippets

Genetics and Histopathology

Classic MFS is due to alteration in microfibrils caused most commonly by mutation of the fibrillin-1 gene (FBN1), which maps to 15q21. This was reported initially in 1991 by Dietz et al.1 Several studies have implicated fibrillin-1 signaling in the structure and function of the extracellular matrix. Fibrillin-1, an extracellular matrix glycoprotein essential to normal fibrinogenesis, is the main component of the 10- to 12-nm microfibrils that together with elastin form elastic fibers found in

Diagnosis

The diagnosis of MFS requires a careful history including information about any family members who may have the disorder or had unexplained sudden death. The modified Ghent criteria, proposed in 1996, allow a uniform approach to the diagnosis of MFS.9 A comprehensive multidisciplinary approach involving cardiac, orthopedic, ophthalmologic, as well as genetic consultations and testing are warranted to confirm the diagnosis. In the absence of a family history of MFS, the diagnosis is made by

Medical Evaluation and Management

The management of patients with MFS optimally involves a multidisciplinary approach. Early diagnosis and treatment are beneficial, and treatment should be tailored to individual manifestations. MFS patients of all ages should undergo at least annual evaluation with clinical history, examination, ophthalmologic evaluation, and an echocardiogram or another aortic imaging study.

Alan C. Braverman: All patients with suspected Marfan syndrome should have a careful evaluation of the face, oral cavity,

Surgical Management

There is general agreement based on a number of comparative studies that overall outcome is improved in MFS patients treated with early aortic root surgery, in addition to continuing beta-blockade.48, 49 Prophylactic surgery is recommended when the diameter of the ascending aorta at the aortic sinuses reaches 5.0 cm.50 Other factors such as family history of aortic dissection, rapid aortic dilatation (aortic root growth >2 mm/y, or >5%/y), severe aortic valve regurgitation with associated

Postoperative Cardiovascular and Medical Care

MFS patients require lifelong medical treatment and surveillance, even after aortic root surgery, representing a major commitment for patient and doctor.

Beta-blockers should be continued indefinitely unless not tolerated. Long-term aspirin and endocarditis prophylaxis should be considered for all postoperative MFS patients. Long-term anticoagulation with warfarin is recommended for patients with mechanical prostheses or in the presence of atrial fibrillation.

Annual cardiovascular and

Marfan Syndrome in Children

It is often difficult to confirm the diagnosis of MFS in children who do not meet the Ghent diagnostic criteria. The features may be subtle initially and develop with age. Children with suspected features of MFS should have repeat evaluation in preschool, before puberty, and at age 18, since some of the clinical manifestations of MFS become evident with age. Serial aortic imaging follow-up is recommended when the aorta is enlarged irrespective of diagnostic criteria. The majority of children

Psychosocial Issues

Social stigmatization can disrupt the ability of individuals with genetic conditions such as MFS to successfully adapt to their situation. Peters et al reported that 56 respondents of a survey of 174 (32%) felt discriminated against or socially devalued because of having MFS.80 Endorsement of discrimination was significantly correlated with having depressive symptoms, low self-esteem, the view MFS had significant negative consequences on one’s life, and perceptions of workplace discrimination.

Pregnancy in Marfan Syndrome

Pregnancy in MFS is possible. There are, however, two major issues that need to be discussed with the patient and family, including the risk of cardiovascular complications in the affected mother and the risk of transmission of MFS to the fetus. Due to the autosomal-dominant nature of the disorder, each offspring of an affected Marfan parent has a 50% chance of inheriting the genetic mutation. Genetic counseling should be encouraged for all patients with MFS. Mutation detection or linkage can

Prognosis

The life expectancy of untreated patients with MFS is significantly reduced, with an early study reporting the lifespan to be about 32 years. However, with beta-blocker therapy and elective surgical repair, the median cumulative probability of survival has increased to over 72 years.86

Summary

Marfan syndrome is a multisystem disorder of connective tissue due to a mutation in the FBN1 gene on chromosome 15. Diagnosis requires delineation of diverse clinical features and evaluation by a variety of specialists. Advances in the understanding of the cause of MFS, as well as timely and accurate diagnosis, have dramatically reduced the mortality and morbidity associated with this disorder through expectant observation and implementation of appropriate prophylactic therapy. We anticipate

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    The authors have no conflicts of interest to disclose.

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