Marfan syndrome: Difference between revisions
No edit summary
Line 108: Line 108:


[[Category:Misc/General]]
[[Category:Misc/General]]
===EVALUATION===
* 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>
'''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 Figure 3, Table 1)<ref>Reference 6 details here.</ref>
* 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
[[File:ASvISED_Trial_Algorithm_and_AORTAs_Algorithm.png|thumb|center|800px|'''Figure 3.''' TOP: (Figure 1 from Peña et al. (2022) – flowchart of ADvISED Trial Algorithm). 
BOTTOM: (Figure 2 from Peña et al. (2022) – flowchart of AORTAs Algorithm).]]
[[File:Pena Summary.png|thumb|center|800px|'''Table 1.''' Summary from Peña et al. (2022) of currently published clinical tools for acute aortic syndrome in the ED, with respective components and scoring systems.]]


===Disposition===
===Disposition===

Revision as of 16:11, 27 August 2025

BACKGROUND [1]

  • Marfan syndrome (MFS) is a heritable connective tissue disorder with multi-system involvement
    • 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
    • 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)
  • 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 & DIAGNOSIC CRITERIA [2]

Revised Ghent Nosology (2010)

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 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
Source: https://step1.medbullets.com/msk/113055/marfan-syndrome

Clinical Features (not all may be present) (Figure 1)

  • 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 of the Following [3]

  • Acute Aortic Syndrome (AAS)
    • Thoracic aortic aneurysm
    • Stanford Types A and B Aortic Dissection
    • Intramural Hemotoma (IMH)
  • Mitral valve prolapse (present in up to 60%) and mitral regurgitation
  • Spontaneous pneumothorax (associated with bullae, 4-11%)
  • Subarachnoid hemorrhage (SAH)[4]
    • Controversial link between Marfan Syndrome and intracranial aneurysms (more clearly associated with vEDS and LDS)
  • Ocular Lens dislocation, retinal detachment
  • Spinal conditions (scoliosis; lumbosacral disease; dural ectasia)
  • Musculoskeletal injuries due to joint laxity (laxity in 85% of children, 56% of adults)
  • 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)
Figure 2. Classification of Aortic Dissection using Stanford and DeBakey systems. Source: ResearchGate

DIFFERENTIAL DIAGNOSIS[2]

  • Classic vs. Kyphoscoliotic vs. Vascular Ehlers-Danlos Syndrome (vEDS)
  • 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

MANAGEMENT

Medications

  • Beta-Blocker (BB) 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.[4]
  • Other Pharmacologic Considerations
    • Avoidance of fluoroquinolones (FQs) due to matrix metalloproteinase (MMP) 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[5]
      • 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[6]
    • Antibiotic prophylaxis is no longer recommended for MFS patients before dental procedures, except in those with artificial heart valves

Lifestyle Modifications[7]

  • 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, GenTAC) as appropriate to help address psychosocial sequelae (e.g., body dysmorphia, anxiety, depression, PTSD, suicidal ideation)

Emergency Management[8][9]

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

See Also

External Links

References

  1. ↑ 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. ↑ 2.0 2.1 The Marfan Foundation. (2025, May 21). The Marfan Foundation | Know the Signs | Fight for Victory. Marfan Foundation. https://marfan.org/
  3. ↑ Dean, J. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007;15:724-733. doi.org/10.1038/sj.ejhg.5201851
  4. ↑ Reference 7
  5. ↑ Reference 8
  6. ↑ Reference 9
  7. ↑ Reference 10
  8. ↑ Reference 11
  9. ↑ Reference 12

References

  1. 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.org/10.1161/STROKEAHA.120.032107
Retrieved from "https://www.wikem.org/w/index.php?title=Marfan_syndrome&oldid=377797"