Marfan syndrome: Difference between revisions
 
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**First characterized as a syndrome by French pediatrician Antoine Marfan in 1896
**First characterized as a syndrome by French pediatrician Antoine Marfan in 1896
**Clinical features vary along a spectrum typical of autosomal-dominant disorders
**Clinical features vary along a spectrum typical of autosomal-dominant disorders
 
*Autosomal-dominant mutation in FBN1 gene (encodes collagen matrix protein fibrillin-1) on chromosome 15<ref name="Milewicz2021">Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. doi:10.1038/s41572-021-00298-7.</ref>
*Autosomal-dominant mutation in FBN1 gene (encodes collagen matrix protein fibrillin-1) on chromosome 15
**This results in cystic medial degeneration of the aortic tunica media (leading to increased risk of aortic aneurysm / dissection)
**This results in cystic medial degeneration of the aortic tunica media (leading to increased risk of aortic aneurysm / dissection)
**This also interferes with elastin deposition during extracellular matrix formation implicates in the elasticity of multiple tissue types
**This also interferes with elastin deposition during extracellular matrix formation implicates in the elasticity of multiple tissue types
**Majority of cases (75%) are familial / inherited vs. minority (25%) are ''de novo'' mutations
**Majority of cases (75%) are familial / inherited vs. minority (25%) are ''de novo'' mutations
 
*Estimated prevalence of 1/5000 individuals worldwide (equal between men and women)<ref name="Milewicz2021">Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. doi:10.1038/s41572-021-00298-7.</ref>
*Estimated prevalence of 1/5000 individuals worldwide (equal between men and women)
 
*Life expectancy for those diagnosed and treated is now close to that of non-MFS population (previously expected increase in patient mortality by third and fourth decades of life)
*Life expectancy for those diagnosed and treated is now close to that of non-MFS population (previously expected increase in patient mortality by third and fourth decades of life)


==Clinical Features==
==Clinical Features==
[[File:Types_of_Dissections.jpg|thumb|Classification of [[Aortic Dissection]] using Stanford and DeBakey systems.<ref>Awal SS, Prasad N, Biswas S. CT evaluation of aortic dissection and other acute aortic syndromes: An Update. Int J Radiol Radiat Ther. 2022;9(5):159‒165. DOI: 10.15406/ijrrt.2022.09.00343</ref>]]
[[File:MarfanChest.jpg|thumb|Pectus excavatum in a person with Marfan syndrome.]]
=== Revised Ghent Nosology (2010)<ref name="MarfanFoundation2025">The Marfan Foundation. (2025, May 21). The Marfan Foundation | Know the Signs | Fight for Victory. Marfan Foundation. https://marfan.org/</ref>===
[[File:Marfan Patient.jpeg|thumb|]]
'''In the absence of family history:'''
[[File:Ectopia Lentis in Marfan syndrome.jpg|thumb|Ectopia lentis in Marfan syndrome with Zonular fibers seen.]]
* Aortic Root Dilatation Z Score > 2 '''and''' Ectopia Lentis
===Physical Findings===
* Aortic Root Dilatation Z Score > 2 '''and''' FBN1 Mutation
''Not all may be present''
* Aortic Root Dilatation Z Score > 2 '''and''' Systemic Score > 7 points
* Ectopia Lentis '''and''' FBN1 Mutation (associated with aortic root dilatation)
 
'''In the presence of family history:'''
* Ectopia Lentis '''and''' Family History of Marfan Syndrome (MFS)
* Systemic Score > 7 points '''and''' Family History of MFS
* Aortic Root Dilatation Z Score > 2 (above 20 years old), > 3 (below 20 years old) '''and''' Family History of MFS
 
===Clinical Features (not all may be present)===
*Tall stature, long extremities  
*Tall stature, long extremities  
*Reduce upper-to-lower segment ratio, increased arm span-to-height ratio
*Reduce upper-to-lower segment ratio, increased arm span-to-height ratio
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*Skin striae
*Skin striae


=== Increased Risk of the Following <ref name="Dean2007">Dean, J. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007;15:724-733. doi.org/10.1038/sj.ejhg.5201851</ref> ===
=== Increased Risk<ref name="Dean2007">Dean, J. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007;15:724-733. doi.org/10.1038/sj.ejhg.5201851</ref> ===
*Acute Aortic Syndrome (AAS)
*Acute Aortic Syndrome (AAS)
**Thoracic aortic aneurysm
**Thoracic aortic aneurysm
**Stanford Types A and B [[aortic dissection]]
**Stanford Types A and B [[aortic dissection]]
**Intramural Hemotoma (IMH)
**Intramural Hemotoma (IMH)
*Mitral valve prolapse (present in up to 60%) and [[mitral regurgitation]]
*[[Mitral valve prolapse]] (present in up to 60%) and [[mitral regurgitation]]
*[[Spontaneous pneumothorax]] (associated with bullae, 4-11%)
*[[Spontaneous pneumothorax]] (associated with bullae, 4-11%)
*[[Subarachnoid hemorrhage]]<ref>4. Kim JH, Woo Kim J, Song S-W, et al. Intracranial aneurysms are associated with Marfan Syndrome: Single cohort retrospective study in 118 patients using brain imaging. Stroke. 2020;52(1):331-334. doi:10.1161/STROKEAHA.120.032107</ref>
*[[Subarachnoid hemorrhage]]<ref>4. Kim JH, Woo Kim J, Song S-W, et al. Intracranial aneurysms are associated with Marfan Syndrome: Single cohort retrospective study in 118 patients using brain imaging. Stroke. 2020;52(1):331-334. doi:10.1161/STROKEAHA.120.032107</ref>
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*Spinal conditions (scoliosis; lumbosacral disease; dural ectasia)
*Spinal conditions (scoliosis; lumbosacral disease; dural ectasia)
*Musculoskeletal injuries due to joint laxity (laxity in 85% of children, 56% of adults)
*Musculoskeletal injuries due to joint laxity (laxity in 85% of children, 56% of adults)
*Complications during pregnancy (risk of [[aortic dissection]])  
*Complications during [[pregnancy]] (risk of [[aortic dissection]])  
**Type A dissection risk increases with aortic dilation; Type B risk poorly understood. ([[aortic dissection]] in up to 4.5%, primarily peripartum)
**Type A dissection risk increases with aortic dilation; Type B risk poorly understood. ([[aortic dissection]] in up to 4.5%, primarily peripartum)


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[[File:ASvISED_Trial_Algorithm_and_AORTAs_Algorithm.png|thumb|TOP: Flowchart of ADvISED Trial Algorithm. BOTTOM: flowchart of AORTAs Algorithm<ref>Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007</ref>.]]
[[File:ASvISED_Trial_Algorithm_and_AORTAs_Algorithm.png|thumb|TOP: Flowchart of ADvISED Trial Algorithm. BOTTOM: flowchart of AORTAs Algorithm<ref>Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007</ref>.]]
[[File:Pena Summary.png|thumb|Summary of currently published clinical tools for acute aortic syndrome in the ED, with respective components and scoring systems.<ref>Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007</ref>]]
[[File:Pena Summary.png|thumb|Summary of currently published clinical tools for acute aortic syndrome in the ED, with respective components and scoring systems.<ref>Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007</ref>]]
===Workup===
* Initial evaluation often occurs in the outpatient setting and involves a thorough physical exam for identification of classically associated features, review of family medical history, slit lamp dilated pupil eye exam (to evaluate for ectopia lentis), and echocardiogram.
* Initial evaluation often occurs in the outpatient setting and involves a thorough physical exam for identification of classically associated features, review of family medical history, slit lamp dilated pupil eye exam (to evaluate for ectopia lentis), and echocardiogram.
* Advancement to specialist involvement, review of transthoracic echocardiography for aortic root dilation / aneurysm / heart valve involvement, potential genetic testing and/or medical genetics consultation per current guidelines.<ref name="Isselbacher2022">Isselbacher EM, Preventza O, Black JH, et al. 2022 ACC/AHA Guideline for the diagnosis and management of aortic disease: A report of the American Heart Association / American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2022;146(24):e334-482. doi.org/10.1161/CIR.0000000000001106</ref>
* Advancement to specialist involvement, review of transthoracic echocardiography for aortic root dilation / aneurysm / heart valve involvement, potential genetic testing and/or medical genetics consultation per current guidelines.<ref name="Isselbacher2022">Isselbacher EM, Preventza O, Black JH, et al. 2022 ACC/AHA Guideline for the diagnosis and management of aortic disease: A report of the American Heart Association / American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2022;146(24):e334-482. doi.org/10.1161/CIR.0000000000001106</ref>


'''Acute Aortic Syndrome (AAS)'''
====Acute Aortic Syndrome (AAS)====
* A high index of suspicion for AAS in the ED setting is critical in MFS when symptoms or signs of this life-threatening complication occur.
* A high index of suspicion for AAS in the ED setting is critical in MFS when symptoms or signs of this life-threatening complication occur.
* '''Key Elements:'''
* '''Key Elements:'''
** Sudden onset of severe, “thunderclap” quality, potentially “tearing” and/or migratory chest, neck, abdominal, and/or back pain
** Sudden onset of severe, “thunderclap” quality, potentially “tearing” and/or migratory chest, neck, abdominal, and/or back pain
** Young patients with few traditional cardiovascular risk factors
** Young patients with few traditional cardiovascular risk factors
** Current or recent pregnancy
** Current or recent [[pregnancy]]
** Family history of aortic aneurysm/dissection or unexplained sudden death
** Family history of [[aortic aneurysm]]/dissection or unexplained sudden death
** Typical “Marfanoid” features may not always be present, especially in non-white patients
** Typical “Marfanoid” features may not always be present, especially in non-white patients
* Clinical decision-making tools and algorithms are available (e.g., ADvISED Trial ADD-RS + D-dimer, AORTAs Algorithms), but are not yet externally validated (see images).<ref>Pena RCF, Hofmann Bowman MA, Ohle R, et al. Algorithms and clinical-decision-making tools for ruling out acute aortic syndrome in the Emergency Department: A narrative review. Italian Journal of Vascular Surgery. 2024;31(1):42-53. doi:10.23736/S1824-4777.23.01623-6</ref>
* Clinical decision-making tools and algorithms are available (e.g., ADvISED Trial ADD-RS + D-dimer, AORTAs Algorithms), but are not yet externally validated (see images).<ref>Pena RCF, Hofmann Bowman MA, Ohle R, et al. Algorithms and clinical-decision-making tools for ruling out acute aortic syndrome in the Emergency Department: A narrative review. Italian Journal of Vascular Surgery. 2024;31(1):42-53. doi:10.23736/S1824-4777.23.01623-6</ref>
* Basic labs, troponin, D-dimer
* Basic labs, [[troponin]], [[D-dimer]]
** '''Important Note:''' D-dimer is not 100% sensitive and cannot exclude all acute aortic syndromes
** '''Important Note:''' [[D-dimer]] is not 100% sensitive and cannot exclude all acute aortic syndromes
* EKG, CXR
* [[EKG]], [[CXR]]
* CTA / MRA aortic protocol (with IV contrast)
* CTA / MRA aortic protocol (with IV contrast)
* Bedside POCUS (Left ventricular outflow tract, aortic root, aortic valve, pericardium, abdominal aorta survey)
* Bedside [[POCUS]] (Left ventricular outflow tract, aortic root, aortic valve, pericardium, abdominal aorta survey)
* Formal TTE / TEE
* Formal [[TTE]] / TEE


'''Other Emergencies'''
====Other Emergencies====
* Standard workup as with non-MFS patients


* Standard workup as with non-MFS patients
===Diagnosis===
==== Revised Ghent Nosology (2010)<ref name="MarfanFoundation2025">The Marfan Foundation. (2025, May 21). The Marfan Foundation | Know the Signs | Fight for Victory. Marfan Foundation. https://marfan.org/</ref>====
'''In the absence of family history:'''
* Aortic Root Dilatation Z Score > 2 '''and''' Ectopia Lentis
* Aortic Root Dilatation Z Score > 2 '''and''' FBN1 Mutation
* Aortic Root Dilatation Z Score > 2 '''and''' Systemic Score > 7 points
* Ectopia Lentis '''and''' FBN1 Mutation (associated with aortic root dilatation)


===Workup===
'''In the presence of family history:'''
* Ectopia Lentis '''and''' Family History of MFS
* Systemic Score > 7 points '''and''' Family History of MFS
* Aortic Root Dilatation Z Score > 2 (above 20 years old), > 3 (below 20 years old) '''and''' Family History of MFS


===Diagnosis===
{{Aortic dissection classification}}


==Management==
==Management==
===Medications===
===Medications===
* '''Beta-Blocker (BB) and/or Angiotensin II Type 1 Receptor Blocker (ARB) Therapy'''
* '''[[Beta-Blocker]] and/or [[Angiotensin II Type 1 Receptor Blocker]] (ARB) Therapy'''
** Beta-blockade lowers blood pressure / heart rate and reduces aortic wall shearing forces to reduce the rate of aortic aneurysm growth and risk of dissection
** Beta-blockade lowers blood pressure / heart rate and reduces aortic wall shearing forces to reduce the rate of aortic aneurysm growth and risk of dissection
** Inhibition of ATII Type 1 Receptor-mediated TGF-beta signaling may reduce elastic tissue degeneration based upon mouse models.<ref>Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007</ref>
** Inhibition of ATII Type 1 Receptor-mediated TGF-beta signaling may reduce elastic tissue degeneration based upon mouse models.<ref>Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007</ref>
* '''Other Pharmacologic Considerations'''
* '''Other Pharmacologic Considerations'''
** Avoidance of fluoroquinolones (FQs) due to matrix metalloproteinase (MMP) activation and increased risk of aortic aneurysm/dissection
** Avoid [[fluoroquinolones]] (FQs) due to matrix metalloproteinase activation and increased risk of aortic aneurysm/dissection
*** Chen S-W et al. (2023) did not show a significant increase in aortic aneurysm/dissection (OR 1.000) in MFS and other high-risk patients after FQ administration.<ref>Chen S-W, Lin C-P, Chan Y-H, et al. Fluoroquinolones and risk of aortic aneurysm or dissection in patients with congenital aortic disease and Marfan Syndrome. Circ J. 2023;87(9):1164-1172. doi:10.1253/circj.cj-22-0682</ref>
*** Chen S-W et al. (2023) did not show a significant increase in aortic aneurysm/dissection (OR 1.000) in MFS and other high-risk patients after FQ administration.<ref>Chen S-W, Lin C-P, Chan Y-H, et al. Fluoroquinolones and risk of aortic aneurysm or dissection in patients with congenital aortic disease and Marfan Syndrome. Circ J. 2023;87(9):1164-1172. doi:10.1253/circj.cj-22-0682</ref>
*** Gopalakrishnan et al. (2020) showed a significant increase in aortic aneurysm/dissection in patients receiving FQs for pneumonia (HR 2.57, p<0.01%), but not UTIs (HR 0.99, p<0.01%). This suggests intrathoracic inflammation from the primary disease pathology, not FQs themselves, increase the risk of aneurysm or dissection.<ref>Gopalakrishnan C, Bykov K, Fischer MA, et al. Association of fluoroquinolones with the risk of aortic aneurysm or [[aortic dissection]]. JAMA Intern Med. 2020;180(12):1596-1605. doi:10.1001/jamainternmed.2020.4199</ref>
*** Gopalakrishnan et al. (2020) showed a significant increase in aortic aneurysm/dissection in patients receiving FQs for pneumonia (HR 2.57, p<0.01%), but not UTIs (HR 0.99, p<0.01%). This suggests intrathoracic inflammation from the primary disease pathology, not FQs themselves, increase the risk of aneurysm or dissection.<ref>Gopalakrishnan C, Bykov K, Fischer MA, et al. Association of fluoroquinolones with the risk of aortic aneurysm or [[aortic dissection]]. JAMA Intern Med. 2020;180(12):1596-1605. doi:10.1001/jamainternmed.2020.4199</ref>
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=== Emergency Management <ref>Reed MJ. Diagnosis and management of [[acute aortic dissection]] in the emergency department. Brit J of Hosp Med. 2024;85(4). doi:10.12968/hmed.2023.0366</ref> <ref>Isselbacher EM, Preventza O, Black JH, et al. 2002 ACC/AHA Guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. JACC. 2022;80(24):e223-e393. doi:10.1016/j.jacc.2022.08.004</ref> ===
=== Emergency Management <ref>Reed MJ. Diagnosis and management of [[acute aortic dissection]] in the emergency department. Brit J of Hosp Med. 2024;85(4). doi:10.12968/hmed.2023.0366</ref> <ref>Isselbacher EM, Preventza O, Black JH, et al. 2002 ACC/AHA Guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. JACC. 2022;80(24):e223-e393. doi:10.1016/j.jacc.2022.08.004</ref> ===


* Evidence-based management of acute aortic dissection:
* Evidence-based management of [[acute aortic dissection]]:
** IV medications to reduce blood pressure (< 100–120 mmHg) and heart rate (< 60 bpm) (e.g., esmolol, labetalol, nitroprusside)
** IV medications to reduce blood pressure (< 100–120 mmHg) and heart rate (< 60 bpm) (e.g., [[esmolol]], [[labetalol]], [[nitroprusside]])
** Emergent vascular, cardiothoracic, or other surgical consultations
** Emergent vascular, cardiothoracic, or other surgical consultations
** Definitive management per current guidelines based on Stanford Type A vs. B dissection, location, extent, and branch involvement
** Definitive management per current guidelines based on Stanford Type A vs. B dissection, location, extent, and branch involvement
* Standard-of-care treatment for other associated pathologies
* Standard-of-care treatment for other associated pathologies


===Disposition===
==Disposition==
* Disposition depends entirely upon the chief complaint, clinical gestalt, and objective findings from physical exam and workup.
* Disposition depends upon the chief complaint, clinical gestalt, and objective findings from physical exam and workup.


== See Also ==
== See Also ==
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[[Category:Misc/General]]
[[Category:Misc/General]]
[[Category:Rheumatology]]

Latest revision as of 17:17, 10 September 2025

Background

  • Marfan syndrome (MFS) is a heritable connective tissue disorder with multi-system involvement[1]
    • First characterized as a syndrome by French pediatrician Antoine Marfan in 1896
    • Clinical features vary along a spectrum typical of autosomal-dominant disorders
  • Autosomal-dominant mutation in FBN1 gene (encodes collagen matrix protein fibrillin-1) on chromosome 15[1]
    • This results in cystic medial degeneration of the aortic tunica media (leading to increased risk of aortic aneurysm / dissection)
    • This also interferes with elastin deposition during extracellular matrix formation implicates in the elasticity of multiple tissue types
    • Majority of cases (75%) are familial / inherited vs. minority (25%) are de novo mutations
  • Estimated prevalence of 1/5000 individuals worldwide (equal between men and women)[1]
  • Life expectancy for those diagnosed and treated is now close to that of non-MFS population (previously expected increase in patient mortality by third and fourth decades of life)

Clinical Features

Pectus excavatum in a person with Marfan syndrome.
Marfan Patient.jpeg
Ectopia lentis in Marfan syndrome with Zonular fibers seen.

Physical Findings

Not all may be present

  • Tall stature, long extremities
  • Reduce upper-to-lower segment ratio, increased arm span-to-height ratio
  • Arachnodactyly (“wrist sign, thumb sign), reduced elbow extension
  • Scoliosis or thoracolumbar kyphosis
  • Pectus excavatum or carinatum
  • Ligamentous laxity, hyperextensibility
  • Protrusio acetabuli
  • Hindfoot deformity, plain flat foot
  • Ectopia lentis
  • Myopia (often severe); retinal detachment
  • Lumbrosacral dural ectasia
  • Dolichocephaly, downward slanting palpebral fissures, enophthalmos, retrognathia, malar hypoplasia, high arched palate
  • Skin striae

Increased Risk[2]

Differential Diagnosis

  • Classic vs. Kyphoscoliotic vs. Vascular Ehlers-Danlos Syndrome (vEDS)[4]
  • Loeys-Dietz Syndrome (LDS)
  • Familial Thoracic Aortic Aneurysm and Dissection (FTAAD)
  • Familial Ectopia Lentis Syndrome
  • MASS Phenotype (Myopia, Mitral Valve Prolapse, Aortic Root Dilatation, Aortic Aneurysm Syndrome, Striae, Skeletal Findings)
  • Shprintzen-Goldberg Syndrome
  • Beals Syndrome
  • Stickler Syndrome
  • Non-Specific Connective Tissue Disorder

Evaluation

TOP: Flowchart of ADvISED Trial Algorithm. BOTTOM: flowchart of AORTAs Algorithm[5].
Summary of currently published clinical tools for acute aortic syndrome in the ED, with respective components and scoring systems.[6]

Workup

  • Initial evaluation often occurs in the outpatient setting and involves a thorough physical exam for identification of classically associated features, review of family medical history, slit lamp dilated pupil eye exam (to evaluate for ectopia lentis), and echocardiogram.
  • Advancement to specialist involvement, review of transthoracic echocardiography for aortic root dilation / aneurysm / heart valve involvement, potential genetic testing and/or medical genetics consultation per current guidelines.[7]

Acute Aortic Syndrome (AAS)

  • A high index of suspicion for AAS in the ED setting is critical in MFS when symptoms or signs of this life-threatening complication occur.
  • Key Elements:
    • Sudden onset of severe, “thunderclap” quality, potentially “tearing” and/or migratory chest, neck, abdominal, and/or back pain
    • Young patients with few traditional cardiovascular risk factors
    • Current or recent pregnancy
    • Family history of aortic aneurysm/dissection or unexplained sudden death
    • Typical “Marfanoid” features may not always be present, especially in non-white patients
  • Clinical decision-making tools and algorithms are available (e.g., ADvISED Trial ADD-RS + D-dimer, AORTAs Algorithms), but are not yet externally validated (see images).[8]
  • Basic labs, troponin, D-dimer
    • Important Note: D-dimer is not 100% sensitive and cannot exclude all acute aortic syndromes
  • EKG, CXR
  • CTA / MRA aortic protocol (with IV contrast)
  • Bedside POCUS (Left ventricular outflow tract, aortic root, aortic valve, pericardium, abdominal aorta survey)
  • Formal TTE / TEE

Other Emergencies

  • Standard workup as with non-MFS patients

Diagnosis

Revised Ghent Nosology (2010)[4]

In the absence of family history:

  • Aortic Root Dilatation Z Score > 2 and Ectopia Lentis
  • Aortic Root Dilatation Z Score > 2 and FBN1 Mutation
  • Aortic Root Dilatation Z Score > 2 and Systemic Score > 7 points
  • Ectopia Lentis and FBN1 Mutation (associated with aortic root dilatation)

In the presence of family history:

  • Ectopia Lentis and Family History of MFS
  • Systemic Score > 7 points and Family History of MFS
  • Aortic Root Dilatation Z Score > 2 (above 20 years old), > 3 (below 20 years old) and Family History of MFS

Aortic Dissection Classification

  • Stanford
    • Type A: Involves any portion of ascending aorta
    • Type B: Isolated to descending aorta
  • De Bakey
    • Type I: Involves the ascending and descending aorta
    • Type II: Involves only the ascending aorta
    • Type III: Involves only the descending aorta
Classification of aortic dissection
Image AoDissect DeBakey1.png AoDissect DeBakey2.png AoDissect DeBakey3.png
Percentage 60% 10–15% 25–30%
Type DeBakey I DeBakey II DeBakey III
Classification Stanford A (Proximal) Stanford B (Distal)

Management

Medications

  • Beta-Blocker and/or Angiotensin II Type 1 Receptor Blocker (ARB) Therapy
    • Beta-blockade lowers blood pressure / heart rate and reduces aortic wall shearing forces to reduce the rate of aortic aneurysm growth and risk of dissection
    • Inhibition of ATII Type 1 Receptor-mediated TGF-beta signaling may reduce elastic tissue degeneration based upon mouse models.[9]
  • Other Pharmacologic Considerations
    • Avoid fluoroquinolones (FQs) due to matrix metalloproteinase activation and increased risk of aortic aneurysm/dissection
      • Chen S-W et al. (2023) did not show a significant increase in aortic aneurysm/dissection (OR 1.000) in MFS and other high-risk patients after FQ administration.[10]
      • Gopalakrishnan et al. (2020) showed a significant increase in aortic aneurysm/dissection in patients receiving FQs for pneumonia (HR 2.57, p<0.01%), but not UTIs (HR 0.99, p<0.01%). This suggests intrathoracic inflammation from the primary disease pathology, not FQs themselves, increase the risk of aneurysm or dissection.[11]
    • Antibiotic prophylaxis is no longer recommended for MFS patients before dental procedures, except in those with artificial heart valves

Lifestyle Modifications [12]

  • Regular blood pressure measurement, lifestyle modification, and titration of antihypertensive therapies with goal BP < 120/80 mmHg
  • Avoidance of high-intensity, high-impact sports and intensive isometric activities / weightlifting
  • Low- to moderate-intensity aerobic activities are encouraged after discussion with a cardiologist or specialist
  • Avoidance of Valsalva and other maneuvers that increase intrathoracic or abdominal pressure (risk of acute dissection)
  • Avoidance/cessation of tobacco, smoking, vaping, or stimulant abuse (e.g., cocaine, methamphetamines)
  • Psychiatric evaluation, resources, and support groups (e.g., Marfan Foundation, oeys-Dietz Syndrome Foundation) as appropriate to help address psychosocial sequelae (e.g., body dysmorphia, anxiety, depression, PTSD, suicidal ideation)

Emergency Management [13] [14]

  • Evidence-based management of acute aortic dissection:
    • IV medications to reduce blood pressure (< 100–120 mmHg) and heart rate (< 60 bpm) (e.g., esmolol, labetalol, nitroprusside)
    • Emergent vascular, cardiothoracic, or other surgical consultations
    • Definitive management per current guidelines based on Stanford Type A vs. B dissection, location, extent, and branch involvement
  • Standard-of-care treatment for other associated pathologies

Disposition

  • Disposition depends upon the chief complaint, clinical gestalt, and objective findings from physical exam and workup.

See Also

External Links

References

  1. ↑ 1.0 1.1 1.2 Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. doi:10.1038/s41572-021-00298-7.
  2. ↑ Dean, J. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007;15:724-733. doi.org/10.1038/sj.ejhg.5201851
  3. ↑ 4. Kim JH, Woo Kim J, Song S-W, et al. Intracranial aneurysms are associated with Marfan Syndrome: Single cohort retrospective study in 118 patients using brain imaging. Stroke. 2020;52(1):331-334. doi:10.1161/STROKEAHA.120.032107
  4. ↑ 4.0 4.1 The Marfan Foundation. (2025, May 21). The Marfan Foundation | Know the Signs | Fight for Victory. Marfan Foundation. https://marfan.org/
  5. ↑ Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007
  6. ↑ Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007
  7. ↑ Isselbacher EM, Preventza O, Black JH, et al. 2022 ACC/AHA Guideline for the diagnosis and management of aortic disease: A report of the American Heart Association / American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2022;146(24):e334-482. doi.org/10.1161/CIR.0000000000001106
  8. ↑ Pena RCF, Hofmann Bowman MA, Ohle R, et al. Algorithms and clinical-decision-making tools for ruling out acute aortic syndrome in the Emergency Department: A narrative review. Italian Journal of Vascular Surgery. 2024;31(1):42-53. doi:10.23736/S1824-4777.23.01623-6
  9. ↑ Pena RCF, Hofmann Bowman MA, Ahmad M, et al. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Seminars in Vasc Surg. 2022;25(1):16-34. doi:10.1053/j.semvascsurg.2022.02.007
  10. ↑ Chen S-W, Lin C-P, Chan Y-H, et al. Fluoroquinolones and risk of aortic aneurysm or dissection in patients with congenital aortic disease and Marfan Syndrome. Circ J. 2023;87(9):1164-1172. doi:10.1253/circj.cj-22-0682
  11. ↑ Gopalakrishnan C, Bykov K, Fischer MA, et al. Association of fluoroquinolones with the risk of aortic aneurysm or aortic dissection. JAMA Intern Med. 2020;180(12):1596-1605. doi:10.1001/jamainternmed.2020.4199
  12. ↑ The Marfan Foundation. (2017). Physical Activity Guidelines. https://marfan.org/wp-content/uploads/2021/09/FINAL-Physical-Activity-Guidelines-11_17.pdf
  13. ↑ Reed MJ. Diagnosis and management of acute aortic dissection in the emergency department. Brit J of Hosp Med. 2024;85(4). doi:10.12968/hmed.2023.0366
  14. ↑ Isselbacher EM, Preventza O, Black JH, et al. 2002 ACC/AHA Guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. JACC. 2022;80(24):e223-e393. doi:10.1016/j.jacc.2022.08.004
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