Table of contents
Marfan syndrome
What's new
Updated 2024 ESC guidelines for the evaluation and management of aortic disease in Marfan syndrome.
Background
Overview
Definition
MS is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, primarily resulting from mutations in the FBN1 gene on chromosome 15.
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Pathophysiology
MS is primarily caused by mutations in the FBN1 gene, which encodes fibrillin-1, a major structural component of the extracellular matrix that provides support to connective tissues, particularly in arteries, the perichondrium, and structures in the eye. These mutations lead to a deficiency or dysfunction of fibrillin-1, disrupting the formation and function of microfibrils in the extracellular matrix. This disruption results in structural abnormalities in various body systems, particularly the skeletal, ocular, and cardiovascular systems.
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Epidemiology
MS is a rare condition with a worldwide prevalence estimated at 15 per 100,000 population. In Europe, the incidence is estimated at 25 per 100,000 person-years in 2021.
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Risk factors
Risk factors for MS include specific gene mutations, particularly in the FBN1, TGFBR1, and TGFBR2 genes. A significant risk factor is a family history of the disease, given its autosomal dominant inheritance pattern. Additional risk factors include advanced paternal age and the presence of certain chromosomal disorders.
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Disease course
It is a multisystem disorder that primarily affects the skeletal, ocular, and cardiovascular systems. Skeletal manifestations include overgrowth of the long bones, resulting in tall stature and disproportionately long limbs and fingers. Other features can include craniofacial characteristics, high-arched palate, positive thumb and wrist signs, scoliosis, and pectus excavatum. Ocular complications often involve dislocation of the ocular lens (ectopia lentis), which can lead to visual impairment. Cardiovascular issues are the most serious and life-threatening aspect of MS, including aortic root aneurysms, aortic dissections, and mitral valve prolapse.
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Prognosis and risk of recurrence
The prognosis largely depends on the severity of cardiovascular complications, which are the primary cause of morbidity and mortality.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of Marfan syndrome are prepared by our editorial team based on guidelines from the European Society of Cardiology (ESC 2024,2021), the Society of Thoracic Surgeons (STS/EACTS 2024), the American Heart Association (AHA/ACC 2022), the European Society of Cardiology (ESC/EACTS 2022), the American Association for Thoracic Surgery (AATS 2021), the Canadian Cardiovascular ...
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Diagnostic investigations
Aortic imaging: as per ESC 2024 guidelines, obtain TTE in patients with MS:
at least annually in patients with an aortic root diameter < 45 mm in the absence of additional risk factors
at least every 6 months in patients with an aortic root diameter < 45 mm in the presence of additional risk factors
at least every 6-12 months in patients with an aortic root diameter ≥ 45 mm in the absence of additional risk factors.
B
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Medical management
Antihypertensive medications
As per ESC 2024 guidelines:
Initiate either a β-blocker or an ARB in maximally tolerated doses (unless contraindicated) to reduce the rate of aortic dilatation in patients with MS.
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Consider initiating both a β-blocker and an ARB in maximally tolerated doses (unless contraindicated) to reduce the rate of aortic dilatation in patients with MS.
B
Nonpharmacologic interventions
Surgical interventions
Aortic aneurysm repair
As per ESC 2024 guidelines:
Perform surgery in patients with MS with aortic root disease with a maximal aortic sinus diameter ≥ 50 mm.
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Consider performing surgery in patients with MS with an aortic root aneurysm with a maximal aortic sinus diameter ≥ 45 mm and additional risk factors.
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More topics in this section
Aortic root replacement
Aortic valve repair