Marfan Syndrome

On your exam of a new patient, a 12-year-old girl, you hear a diastolic murmur in left upper sternal border as well as a mid-systolic click with late systolic murmur. You also notice she has long, thin limbs and a positive thumb sign and wrist sign.

What further evaluation would you perform? 

The above case is representative of Marfan Syndrome (MFS), and given the incidence, it is important for general pediatricians to be aware of the common features and management.

Epidemiology and Genetics

  • Incidence is 1 in 3,000-5,000 people  
  • No strong variation among ethnicity
  • Autosomal dominant
  • Most individuals have affected relative, but 25% de novo mutation
  • Highly variable expression
  • >90% have mutations in FBN1 gene
    • Encodes the connective tissue protein, fibrillin-1
    • Large gene (65 exons) located on chromosome 15q-21.1
    • Causes systemic weakness of connective tissue
  • <10% have mutation in TGF-beta receptor 1 or 2 (TGFBR1 or TGFBR2)

Physical Features and Clinical Manifestations

Multiple organ systems are affected by MFS. The presentation varies widely from a rapidly progressive, fatal neonatal form to isolated organ involvement.


  • Tall stature
  • Abnormal body proportions: reduced upper segment to lower segment ratio and increased arm span to height ratio
  • Long, thin extremities compared to trunk size (dolichostenomelia)
  • Long fingers (arachnodactyly): look for “thumb sign” and “wrist sign”)

Thumb sign; upper: normal, lower: Marfan syndrome.

  • Joint hypermobility (OR reduced joint mobility) 
  • Pectus carinatum (more specific) or pectus excavatum


  • Scoliosis/kyphosis
  • Torticollis
  • Flat feet (pes planus)
  • Acetabular protrusion
  • Long face


  • Lens dislocation (ectopia lentis)


  • Iridodonesis (rapid contraction and dilation of the iris)
  • Myopia (elongation of the globe)


  • Aortic dissection
  • Aortic root dilation leading to aortic regurgitation
  • Mitral valve prolapse


  • Spontaneous pneumothorax (due to emphysematous change causing bullae formation)
  • Reduced pulmonary reserve


  • Striae


  • Dural Ectasia (stretching of dural sac in lumbosacral region
  • Inguinal hernias
  • High palate arch (“steepled”)
  • Crowded teeth
  • Sleep apnea

Differential Diagnosis

  • Loeys-Dietz syndrome (LDS)
  • Shprintzen-Goldberg syndrome (SGS)
  • MASS (mitral valve prolapse, mid aortic dilatation, striae atrophica, skeletal features) phenotype
  • Mitral valve prolapse syndrome
  • Congenital contractural arachnodactylyl (CCA)
  • Homocystinuria 
  • Ehlers-Danlos syndrome
  • Klinefelter's syndrome

Evaluation and Diagnostic Criteria

Diagnosis of Marfan syndrome is based on the revised Ghent nosology (

  • Based on the degree of aortic root dissection (Z-score calculator available at, presence of ectopia lentisfamily history of MFS, and systemic score based on phenotypic traits.
  • It can be challenging to apply diagnostic criteria to children < 20 years as some disease features are not yet present and become more apparent with age.
  • Additional categories of “nonspecific connective tissue disorder” and “potential MFS” can be used for those children without clear inclusion criteria.

Systemic involvement can be gauged using a point system with a score ≥7, which indicates major systemic involvement (



Aortic disease is the most common cause of morbidity and mortality for patients with Marfan syndrome.

  • Aortic monitoring begins with echocardiogram performed at the time of diagnosis and 6 months later to determine aortic root and diameter size and rate of enlargement (2010 ACC/AHA/AATS)
  • With evidence of progressive aortic root dilation, beta-blockers should be prescribed as they help decrease wall stress (e.g., propranolol, atenolol, metoprolol), although efficacy in children has limited data.
  • Addition of an angiotensin II receptor blocker (e.g., losartan) to slow the progression of aortic root dilation may be beneficial, though clinical data is limited

Signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and progression. Therefore, regular exams are important for surveillance and intervention

  • Annual ophthalmologic examination for myopia and lens dislocation (especially as young children as they are at high risk for amblyopia)
  • Annual echocardiograms to monitor status of aortic root dilatation, aortic dissection, aortic tear or rupture, aortic regurgitation, mitral valve prolapse, tricuspid valve prolapse, and/or enlargement of the proximal pulmonary artery
  • Intermittent surveillance of the entire aorta with CT or MRA scans beginning in young adulthood
  •  Close monitoring for aneurysms and aortic arch dissection 

Other considerations include the following:

  • Restriction or limitation of vigorous physical exercise (low to moderate activity permissible)
  • Avoidance of sports with high risk of eye injury (ex. boxing, karate)
  • Elective surgical repair of the aorta and valves
  • Orthodontics for oromaxillofacial anomalies
  • Pulmonary function tests if significant respiratory complaints
  • Braces or surgery for scoliosis
  • Orthopedic intervention for complications of joint laxity
  • Screening of first degree relatives with echocardiogram
  • Genetic counseling
  • Support groups (ex. National Marfan Foundation)


Patient Resources



  1. Genetics, clinical features, and diagnosis of Marfan Syndrome.  UptoDate.
  2. Management of Marfan syndrome and related disorders - UpToDate. https://www-uptodate-com/contents/management-of-marfan-syndrome-and-rela...
  3. Tinkle BT, Saal HM. Health supervision for children with Marfan syndrome. Pediatrics. 2013 Oct;132(4):e1059-72. PubMed PMID: 24081994
  4. The Marfan Foundation. 2015. Z-score Calculation. Retrieved from
  5. Genetics Home Reference. 2012 . Marfan Syndrome. Retreived from
  6. Online Mendelian Inheritance in Man. 2015. Marfan Syndrome. Retrieved from
  7. National Human Genome Research Institute.2014 .learning about Marfan syndrome. Retrieved from


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