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Marfan syndrome

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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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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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 American Heart Association (AHA/ACC 2022), the European Society of Cardiology (ESC/EACTS 2021), the European Society of Cardiology (ESC 2021; 2014), the American Association for Thoracic Surgery (AATS 2021), the Canadian Cardiovascular Society (CCS/CHRS 2019), the European Society for Vascular Surgery (ESVS 2017), the Canadian Cardiovascular Society (CCS 2014), and the Society for Cardiovascular Angiography and Interventions (SCAI/STS/SVM/AATS/SCA/AHA/ACR/ACC/ASA/SIR 2010).
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Guidelines

1.Diagnostic investigations

Aortic imaging
As per ACC 2022 guidelines:
Obtain a TTE at the time of initial diagnosis to determine the diameters of the aortic root and ascending aorta, and 6 months thereafter to determine the rate of aortic growth in patients with MS. Obtain an annual surveillance TTE if the aortic diameters are stable. Obtain CT or MRI of the thoracic aorta if the aortic root, ascending aorta, or both, are not adequately visualized on TTE.
B
Consider obtaining CT or MRI of the thoracic aorta to confirm the aortic diameters and assess the remainder of the thoracic aorta after an initial TTE in adult patients with MS.
C
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2.Medical management

Antihypertensive medications
As per ACC 2022 guidelines:
Initiate either β-blockers or ARBs in maximally tolerated doses (unless contraindicated) to reduce the rate of aortic dilation in patients with MS.
A
Consider initiating both a β-blocker and an ARB in maximally tolerated doses (unless contraindicated) to reduce the rate of aortic dilation in patients with MS.
C

3.Nonpharmacologic interventions

Physical activity restrictions: consider restricting sports participation in patients with MS with aortic dilatation.
B

4.Surgical interventions

Aortic aneurysm repair: as per ACC 2022 guidelines, perform open repair over endovascular repair in patients with MS and intact thoracoabdominal aortic aneurysm requiring intervention.
B

More topics in this section

  • Aortic aneurysm repair (ECS)

  • Aortic root replacement

  • Aortic dissection repair

  • Aortic valve repair

5.Specific circumstances

Patients contemplating pregnancy: as per ACC 2022 guidelines, perform aortic surgery before pregnancy in patients with MS and an aortic root diameter > 4.5 cm.
B
consider performing aortic surgery before pregnancy if the aortic root diameter is 4.0-4.5 cm, especially if there are risk factors for aortic dissection, such as rapid aortic growth of ≥ 0.3 cm/year or a family history of aortic dissection.
B

6.Patient education

Pregnancy counseling: as per ACC 2022 guidelines, provide genetic counseling before pregnancy to discuss the heritable nature of their condition in patients with MS contemplating pregnancy.
B