ICCnotes

Evidence-based clinical reference for inherited cardiac conditions, genetics, risk, treatment & guidelines

Marfan Syndrome (MFS)

Quick Summary

Definition: A systemic autosomal dominant connective tissue disorder caused by FBN1 variants, with skeletal, ocular and cardiovascular features, notably aortic root dilatation and dissection risk.[1]

  • Prevalence: 1 in 5,000 (most common heritable aortopathy)[1]
  • Key gene: FBN1 (fibrillin-1), autosomal dominant, ~25% de novo
  • Hallmark: Aortic root dilatation (Z≥2) + ectopia lentis + skeletal features (Ghent criteria)
  • High-risk markers: Aortic root >45mm, rapid growth (>3mm/year), family history dissection, pregnancy
  • First-line Mx: Beta-blockers (target HR 60-70), annual echo, prophylactic surgery >50mm (or >45mm if risk factors)

Aetiology

Monogenic (Mendelian): ~100%, FBN1 variant (~25% de novo)[1]

Genetics

Inheritance: Autosomal dominant. Each child of an affected person has a 50% chance of inheriting the variant; risk to parents and siblings depends on whether the variant was inherited or arose de novo (low-level parental mosaicism is possible), so it is set by parental testing and the pedigree.[1]

Familial vs de novo: Approximately 75% of cases are familial (inherited from an affected parent); approximately 25% arise as de novo FBN1 mutations with no family history of Marfan syndrome.[1]

Gene: FBN1 (fibrillin-1), >90% of cases meeting revised Ghent criteria

Penetrance: ~100%, but expressivity is highly variable, the same mutation can cause mild or severe disease even within the same family

Prevalence

1 in 5,000 to 1 in 10,000[1]

No ethnic or sex predilection

~25% de novo mutations

Diagnostic Criteria

Revised Ghent Nosology (2010)

In absence of family history:

  • Aortic root dilatation (Z-score ≥2) AND ectopia lentis, OR
  • Aortic root dilatation AND FBN1 mutation, OR
  • Aortic root dilatation AND systemic score ≥7*, OR
  • Ectopia lentis AND FBN1 mutation with known aortic disease

With family history:

  • Ectopia lentis, OR
  • Systemic score ≥7*, OR
  • Aortic root dilatation (Z ≥2 if age ≥20y, Z ≥3 if <20y)*

* Only after Shprintzen-Goldberg, Loeys-Dietz and vascular Ehlers-Danlos syndromes have been excluded, with TGFBR1/TGFBR2, COL3A1 or other testing as indicated[1].

Systemic score (maximum 20; ≥7 indicates systemic involvement):[1]

PointsFeature
3Wrist AND thumb sign (wrist OR thumb sign alone: 1)
2Pectus carinatum (pectus excavatum or chest asymmetry: 1)
2Hindfoot deformity (plain pes planus: 1)
2Pneumothorax
2Dural ectasia
2Protrusio acetabuli
1Reduced upper-to-lower segment ratio AND increased arm span-to-height ratio, without severe scoliosis
1Scoliosis or thoracolumbar kyphosis
1Reduced elbow extension
1Facial features (3 of 5: dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)
1Skin striae
1Myopia >3 dioptres
1Mitral valve prolapse

Diagnosis

Confirming the diagnosis: see the revised Ghent nosology criteria above.[1] Core work-up: echocardiography (aortic root Z-score) and slit-lamp ophthalmology (ectopia lentis) in every suspected case; FBN1 genetic testing is strongly recommended (and is essential for cascade testing of relatives), but the revised Ghent criteria allow a clinical diagnosis in some patients without a detected FBN1 variant, so genetic testing is not an absolute requirement for diagnosis in every case.

Cardinal cardiovascular features:

  • Aortic root aneurysm (most important - risk of dissection)
  • Aortic regurgitation
  • Mitral valve prolapse, mitral regurgitation
  • Aortic dissection

Skeletal features: Tall stature, arachnodactyly, pectus deformity, scoliosis, reduced upper:lower segment ratio

Ocular: Ectopia lentis (lens dislocation)

Investigations

Echocardiography: aortic root at the sinuses of Valsalva and the ascending aorta, expressed as Z-scores for age and body size; aortic and mitral valves (prolapse, regurgitation); LV size and function.[1][6]

Whole-aorta imaging: CT or MR angiography of the entire aorta at baseline and during follow-up (see Follow-up), and whenever echo views are suboptimal. MRI is preferred for repeated imaging in young people to limit radiation.[2][6]

After aortic root surgery: lifelong imaging of the remaining aorta, since dissection or aneurysm of the arch and descending aorta is the main late aortic risk after root replacement.[6]

ECG and ambulatory monitoring: ventricular ectopy and NSVT, particularly where there is LV dilatation or significant mitral valve prolapse.[10]

Genetic testing: FBN1 sequencing; multi-gene panel (including FBN2, TGFBR1/2) if FBN1-negative[1]

Ophthalmology: Slit-lamp examination for ectopia lentis

Skeletal assessment: the features needed to calculate the systemic score (see Diagnostic Criteria).[1]

Treatments

1. General measures:

  • Avoid heavy lifting, isometric exercise, contact sports, competitive sports
  • Moderate aerobic activity (low-intensity) generally acceptable
  • Genetic counselling and family cascade testing, see the Genetic Testing page

2. Medical therapy:

  • Aims to reduce aortic growth rate[2]
  • Beta-blockers (first-line):
    • Atenolol (most evidence in Marfan; the Pediatric Heart Network trial found atenolol and losartan similarly effective at slowing aortic-root dilatation in children and young adults[7]):
      • Start 25–50 mg once daily → target 50–100 mg once daily
      • Target resting HR <60–70 bpm and blunted exercise HR response
      • Dose to maximum tolerated; avoid underdosing
    • Bisoprolol (alternative):
      • Start 2.5 mg once daily → target 5–10 mg once daily
      • Preferred if atenolol not tolerated or renal impairment
    • Propranolol (alternative, non-selective):
      • Start 20–40 mg twice daily → target 80–160 mg twice daily
  • Losartan, additive to beta-blocker (ESC Class IIa):
    • Start 25–50 mg once daily → target 100 mg once daily (or maximum tolerated)[5]
    • COMPARE trial: losartan reduced the aortic-root dilatation rate in adults with Marfan syndrome[8]. The AIMS trial separately found irbesartan slowed aortic-root dilatation in children and young adults[9]. Overall, ARBs and beta-blockers each modestly slow aortic growth, with no clear superiority of one class[3]
    • Avoid in pregnancy, switch to beta-blocker monotherapy pre-conception
    • Monitor K⁺ and renal function; check BP (target systolic <130 mmHg)

3. Surgery:

  • Prophylactic aortic root replacement if diameter ≥50 mm (≥45 mm if family history of dissection, rapid growth >3 mm/year, or concurrent surgery planned)[2][6]
  • Valve-sparing root replacement (David/Yacoub procedure) preferred if aortic valve pliable and not regurgitant

4. Advanced heart failure and/or transplant referral:

  • Standard advanced-heart-failure pathways apply if severe valve disease leads to LV dysfunction and refractory heart failure
Related Resources

Complications

  • Aortic root aneurysm: progressing to dissection or rupture, the principal life-threatening complication[1]
  • Aortic and mitral regurgitation: and mitral valve prolapse
  • Pregnancy-associated dissection: with risk rising with root size and in the peripartum period
  • Multisystem features: ectopia lentis and retinal detachment, spontaneous pneumothorax, dural ectasia and scoliosis
  • Distal aortic dissection or aneurysm: particularly after root replacement, hence lifelong imaging of the remaining aorta[6]
  • Myocardial involvement: mild LV dilatation or systolic dysfunction beyond what valve disease explains, with ventricular arrhythmia[10]

Risk Stratification

Aortic dissection risk increases with:[2][6]

  • Root diameter ≥50 mm, or ≥45 mm with additional risk factors
  • Growth of more than 3 mm per year
  • Family history of dissection
  • Pregnancy and the postpartum period
  • Previous aortic surgery, after which the distal aorta remains at risk

Body size: interpret diameters relative to body size, particularly in children and small adults.[6]

Arrhythmia: ventricular arrhythmia is more frequent than in the general population and arrhythmic sudden death occurs independently of valve disease; in adults with FBN1 variants it was associated with raised NT-proBNP and LV dilatation.[10]

Life expectancy: Near normal with appropriate management

Pregnancy Management

mWHO class II–III or above: refer to a Pregnancy Heart Team before conception (see Pregnancy).

Pregnancy in Marfan syndrome - individualized risk assessment

Pregnancy risk in Marfan syndrome is not determined by aortic root diameter alone. Risk assessment should incorporate indexed aortic root and ascending aorta measurements, growth rate, any previous dissection, family history of dissection, valve disease (aortic or mitral regurgitation) and, where known, genotype. A larger root or a history of dissection materially raises risk, but there is no single diameter cut-off (e.g. 40 mm or 45 mm) above which pregnancy should be described as universally contraindicated. The mWHO framework used by the ESC pregnancy guideline nonetheless classes a root of 40–45 mm as high risk (mWHO III) and >45 mm as very high risk (mWHO IV), and these categories should be discussed in counselling; the decision itself is individualized.[1][4]

Pre-pregnancy assessment: baseline echocardiography (aortic root and ascending aorta) and, where indicated by prior imaging gaps or dimensions, CT/MR angiography of the whole aorta; review of prior surgery, growth trend and family history; genetic counselling (genetic testing is strongly recommended, but the revised Ghent criteria allow a clinical diagnosis in some patients even without a detected FBN1 variant, so a negative genetic test does not exclude the diagnosis).[1]

During pregnancy: beta-blockers are generally continued; ACE inhibitors and ARBs (including losartan) are stopped before conception as they are teratogenic. Imaging frequency should be individualized to the patient's baseline dimensions and growth rate rather than a fixed monthly schedule for everyone; more frequent surveillance is reasonable for a larger or growing aorta, less frequent for a stable, normal-range aorta.[4]

Surgery before pregnancy: recommended if the root is >45 mm (I); may be considered at 40–45 mm with growth >3 mm/year or a family history of aortic dissection (IIb).[4]

Delivery: vaginal delivery is recommended if the aorta is <40 mm (I); at 40–45 mm, vaginal delivery with epidural anaesthesia and an expedited second stage should be considered (IIa) and caesarean may be considered (IIb); at ≥45 mm, or with aortic dissection, caesarean should be considered (IIa). The plan is agreed by the Pregnancy Heart Team on aortic status at the time.[4]

Postpartum: most postpartum dissections occur in the first week: a postpartum echocardiogram is done (repeated before discharge if high risk) and a stay of up to a week may be planned for women at high risk[11]. Imaging continues until 6 months postpartum[4], with patient education about urgent symptoms (chest, back or abdominal pain).

Contraception and future pregnancy: discuss the full range of options, including long-acting reversible contraception and permanent methods, through non-directive counselling; the decision, including whether to consider a future pregnancy, is led by the patient.

Follow-up

Based on the 2024 ESC aortic & peripheral arterial diseases (PAAD) guideline and the revised Ghent nosology[2][1][6].

Advanced / complicated = aortic root ≥45 mm, growth >3 mm/year, prior dissection or repair, significant valve disease, or pregnancy.

Genotype-positive / phenotype-negative (G+/P−) = a confirmed pathogenic-variant carrier with no overt disease expression yet.

Genotype+ / Phenotype−Uncomplicated / StableAdvanced / Complicated
FrequencyAnnual (FBN1+ even if no features)AnnualEvery 6 months (or sooner)
Clinical reviewSymptoms, BP control, medicationSymptoms, BP control, medication adherenceAs above
Echocardiography (aortic root)AnnualAnnual if stable and <45 mm6-monthly if ≥45 mm or growing
CT / MR angiography (whole aorta)BaselineBaseline, then every 1–2 yearsAnnual or sooner
Ophthalmology / skeletalPeriodic (ectopia lentis, skeletal)Periodic (ectopia lentis, scoliosis)As needed
PregnancyPre-conception counsellingPre-conception aortic assessment & counsellingAortic imaging during pregnancy, frequency individualised (often each trimester if stable, more frequently for a larger or growing aorta)
Family screening–Cascade imaging ± genetics–

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

Key Points

  • Genetic counselling - 50% risk to offspring[1]
  • Screen first-degree relatives
  • Pregnancy risk rises substantially with a larger or growing aortic root or prior dissection; there is no single universal diameter cut-off, and the decision (including consideration of prophylactic surgery before conception) should be individualized by an aortopathy/Pregnancy Heart Team[1]
  • Risk rises as the aortic root enlarges, and mWHO categories are commonly applied in this direction: a root under 40mm is treated as lower risk (though dissection still occurs), 40-45mm as high risk, and around or above 45mm as very high risk falling into mWHO IV in many frameworks. Apply these as a guide to intensity of care and counselling rather than as fixed thresholds, since the classification varies between guidelines and the assessment also depends on growth rate, prior dissection, family history, valve disease and genotype
  • Beta-blockers throughout pregnancy unless contraindicated; dose and heart-rate goal individualised[1]
  • Delivery at tertiary centre with cardiothoracic surgery on-site
  • Lifelong surveillance required - annual imaging[1]

References & Review Date

Last reviewed: October 2026

Key studies in Marfan syndrome · the landmark studies, drawn to scale with the other inherited cardiac conditions.

  1. Loeys BL, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–485. doi:10.1136/jmg.2009.072785
  2. Erbel R, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. Eur Heart J. 2014;35(41):2873–2926. doi:10.1093/eurheartj/ehu281
  3. Milleron O, et al. Marfan Sartan: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2015;36(32):2160–2166. doi:10.1093/eurheartj/ehv151
  4. De Backer J, Haugaa KH, et al. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy. Eur Heart J. 2025;46(43):4462–4568. doi:10.1093/eurheartj/ehaf193
  5. Joint Formulary Committee. British National Formulary (BNF). Losartan potassium. bnf.nice.org.uk/drugs/losartan-potassium
  6. Mazzolai L, Teixido-Tura G, Lanzi S, et al. 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. Eur Heart J. 2024;45:3538–3700. doi:10.1093/eurheartj/ehae179
  7. Lacro RV, et al. Atenolol versus losartan in children and young adults with Marfan's syndrome (Pediatric Heart Network). N Engl J Med. 2014;371(22):2061–2071. doi:10.1056/NEJMoa1404731
  8. Groenink M, et al. Losartan reduces aortic dilatation rate in adults with Marfan syndrome (COMPARE): a randomized controlled trial. Eur Heart J. 2013;34(45):3491–3500. doi:10.1093/eurheartj/eht334
  9. Mullen M, et al. Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial. Lancet. 2019;394(10216):2263–2270. doi:10.1016/S0140-6736(19)32518-8
  10. Aydin A, Adsay BA, Sheikhzadeh S, et al. Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations. PLoS One. 2013;8(12):e81281. doi:10.1371/journal.pone.0081281
  11. Royal College of Obstetricians and Gynaecologists. Prevention and management of aortic dissection in pregnancy. Good Practice Paper No. 20. August 2026. rcog.org.uk