Marfan Syndrome—Diagnosis and Management
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
References (87)
- et al.
Marfan’s syndrome
Lancet
(2005) - et al.
A bioinformatics framework for genotype-phenotype correlation in humans with Marfan syndrome caused by FBN1 gene mutations
J Biomed Inform
(2006) - et al.
Valve-sparing aortic root replacement in Marfan syndrome
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu
(2005) - et al.
Comparison of aortic dissection in patient with and without Marfan’s syndrome (results from the International Registry of Aortic Dissection)
Am J Cardiol
(2004) - et al.
Characterizing the young patient with aortic dissection: results from the International Registry of Aortic Dissection (IRAD)
J Am Coll Cardiol
(2004) - et al.
Two-dimensional echocardiographic aortic root dimensions in normal children and adults
Am J Cardiol
(1989) - et al.
A critical analysis of minor cardiovascular criteria in the diagnostic evaluation of patients with Marfan syndrome
Genet Med
(2006) Cerebral infarction in a young adult with Marfan syndrome
Int J Cardiol
(2006)- et al.
Left ventricular function in the Marfan syndrome without significant valvular regurgitation
Am J Cardiol
(2003) - et al.
Familial thoracic aortic aneurysms and dissections—incidence, modes of inheritance, and phenotypic patterns
Ann Thorac Surg
(2006)
Comparison of the pattern of aortic dilation in children with the Marfan’s syndrome versus children with a bicuspid aortic valve
Am J Cardiol
Determinants of rapid progression of aortic root dilatation and complications in Marfan syndrome
Int J Cardiol
Aortic root growth in men and women with the Marfan’s syndrome
Am J Cardiol
Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms
Ann Thorac Surg
Aortic wall mechanics in the Marfan syndrome assessed by transesophageal tissue Doppler echocardiography
Am J Cardiol
Choice of computed tomography, transesophageal echocardiography, magnetic resonance imaging, and aortography in acute aortic dissection: International Registry of Acute Aortic Dissection (IRAD)
Am J Cardiol
Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome
Am J Cardiol
Usefulness of enalapril versus propranolol or atenolol for prevention of aortic dilation in patients with the Marfan syndrome
Am J Cardiol
Natural history of thoracic aortic aneurysms: indications for surgery and surgical versus nonsurgical risks
Ann Thorac Surg
Aortic root replacement in 271 Marfan patients: a 24-year experience
Ann Thorac Surg
Results of surgery for aortic root aneurysm in patients with Marfan syndrome
J Thorac Cardiovasc Surg
Long-term results of aortic valve-sparing operations for aortic root aneurysm
J Thorac Cardiovasc Surg
Valve-sparing aortic root reconstruction in patients with significant aortic insufficiency
Ann Thorac Surg
Results of aortic valve-sparing operations: experience with remodeling and reimplantation procedures in 65 patients
Ann Thorac Surg
Risk factors for rupture of chronic type B dissections
J Thorac Cardiovasc Surg
Mitral valve surgery in the adult Marfan syndrome patient
Ann Thorac Surg
Should the transverse aortic arch be replaced simultaneously with aortic root replacement for annuloaortic ectasia in Marfan syndrome?
J Thorac Cardiovasc Surg
Treatment of a fistula at the distal anastomosis after Bentall operation with endoluminal covered stent
Ann Thorac Surg
Fate of coronary ostial anastomoses after the modified Bentall procedure
Ann of Thorac Surg
Effect of beta-blockade on ascending aortic dilatation in children with the Marfan syndrome
Am J Cardiol
Surgery for aortic root aneurysm in children: a 21-year experience in 50 patients
Ann Thorac Surg
ACC/AHA 2006 guidelines for the management of patients with valvular heart disease
J Am Coll Cardiol
Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome
Am J Cardiol
A prospective longitudinal evaluation of pregnancy in the Marfan syndrome
Am J Obstet Gynecol
Obstetric complications in Marfan syndrome
Int J Cardiol
Life Expectancy in the Marfan Syndrome
Am J Cardiol
Marfan Syndrome caused by a recurrent do novo missense mutation in the fibrillin gene
Lett Nat
Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome
Nat Genet
Molecular genetics of Marfan syndrome
Curr Opin Cardiol
FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited
Am J Med Genet Part A
The molecular genetics of Marfan syndrome and related disorders
J Med Genet
Revised diagnostic criteria for the Marfan Syndrome
Am J Med Genet
Cited by (148)
Favorable long term clinical outcomes in two patients with neonatal Marfan syndrome
2024, Progress in Pediatric CardiologySelf-navigated 3D whole-heart MRA for non-enhanced surveillance of thoracic aortic dilation: A comparison to CTA
2021, Magnetic Resonance ImagingAneurysmatic degeneration of connective tissue diseases: from diagnosis to treatment
2021, Vascular Surgery: A Clinical Guide to Decision-makingOral health in patients with Marfan syndrome
2020, Archives of Oral Biology
The authors have no conflicts of interest to disclose.