Ver el código de «Marfan syndrome»

==Background==
*Marfan syndrome (MFS) is a heritable [[connective tissue disorder]] with multi-system involvement<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>
**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==
[[File:Types_of_Dissections.jpg|thumb|Classification of Aortic Dissection using Stanford and DeBakey systems.<ref>CT evaluation of aortic dissection and other acute aortic syndromes: An update [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>]
=== 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)

'''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 
*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 <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)
**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]]<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>
**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)

==Differential Diagnosis ==
* Classic vs. Kyphoscoliotic vs. [https://marfan.org/conditions/veds/ Vascular Ehlers-Danlos Syndrome (vEDS)]<ref name="MarfanFoundation2025"/>
* [https://marfan.org/conditions/loeys-dietz/ 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==
[[File:ASvISED_Trial_Algorithm_and_AORTAs_Algorithm.png|thumb|'''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|'''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.]]
* 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>6. 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
** '''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

===Workup===

===Diagnosis===

==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.<ref>7. 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'''
** 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.<ref>8. 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>9. 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>
** Antibiotic prophylaxis is no longer recommended for MFS patients before dental procedures, except in those with artificial heart valves

===  Lifestyle Modifications <ref>10. The Marfan Foundation. (2017). Physical Activity Guidelines. https://marfan.org/wp-content/uploads/2021/09/FINAL-Physical-Activity-Guidelines-11_17.pdf</ref> ===
* 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 <ref>11. 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>12. 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:
** 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 ==
* [[Connective tissue disease]]
* [[Nontraumatic thoracic aortic dissection]]
* [[Ehlers-Danlos syndrome]]
* [[EBQ:IRAD]]

== External Links ==
* [https://marfan.org/ Marfan Foundation]
* [https://marfan.org/resources/professionals/ Marfan Foundation (Resources for Physicians)]
* [https://www.gentacalliance.org/ Genetic Aortic Network - formerly GenTAC Alliance]
* [https://www.iradonline.org/ International Registry of Acute Aortic Dissection (IRAD)]

== References ==
<references/>

[[Category:Misc/General]]