Physical Examination
Given the variable expressivity of Marfan syndrome (MFS), no single sign is pathognomic. The diagnosis is made on clinical grounds on the basis of typical abnormalities (see the image below).
Adult with Marfan syndrome. Note tall and thin build, disproportionately long arms and legs, and kyphoscoliosis.
The cardiac, skeletal, and ocular systems are generally more focused upon for MFS diagnostic criteria; however, other tissues, including skeletal muscle, fat, skin, fascia, and the respiratory tract, may be affected in this condition as well. [18, 16] In a prospective study by Sponseller et al, the physical examination features with the highest diagnostic yield were as follows [14] :
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Craniofacial characteristics
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Thumb and wrist signs
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Pectus carinatum
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Severe hindfoot valgus
Clinical Diagnostic Criteria for Marfan Syndrome
The following list describes the most common clinical findings and the revised Berlin criteria (1986) for diagnosis of MFS. In 1996, the Ghent criteria updated the previous guidelines to include greater emphasis on the skeletal findings, as well as those of the family and genetic history. The Ghent criteria were subsequently updated in 2010 (see below), [20, 21, 22, 23] the main difference from the 1996 criteria being that more weight was given to aortic root aneurysm and ectopia lentis. (See Genetics of Marfan Syndrome.)
Skeletal system
For the skeletal system involvement to be used as criteria for the diagnosis, at least two major criteria or one major criterion plus two minor criteria must be present.
Major skeletal system criteria are as follows:
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Pectus carinatum
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Pectus excavatum requiring surgery
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A reduced upper-to-lower segment ratio (ie, the distance from the head to the pubic symphysis divided by the distance of the pubic symphysis to the sole) of less than 0.85
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An increased arm span–to–height ratio that is greater than 1.05
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A positive wrist sign (ie, the thumb and index fingers overlap when encircling the contralateral wrist.)
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A positive thumb (Steinberg) sign (ie, the thumb extends beyond the ulnar border of the hand when the digit is held flexed in the palm.)
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A thoracolumbar scoliosis of more than 20º or spondylolisthesis
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Progressive collapse of the hindfoot, leading to pes planovalgus deformity
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A protrusio acetabuli of any degree (seen on anteroposterior [AP] radiographs of the pelvis)
Minor skeletal system criteria are as follows:
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Pectus excavatum of moderate severity
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Joint hypermobility
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High arched palate, with dental crowding
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Facial appearance (dolichocephaly, malar hypoplasia, enophthalmos, retrognathia, down-slanting palpebral fissures)
Ocular system
For ocular system involvement to be used as diagnostic criteria, the major criterion or at least two minor criteria must be present. [13]
The ocular system major criterion is ectopia lentis (lens dislocation). [24]
Minor ocular system criteria are as follows:
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An abnormally flat cornea
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An increased axial length of the globe, as measured by ultrasonography (US)
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A hypoplastic iris or hypoplastic ciliary muscle, causing myopia
Cardiovascular system
For cardiovascular system involvement to be considered diagnostic criteria, only one of the major or minor criteria must be present. [25, 26]
Major cardiovascular system criteria are as follows:
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Dilatation of the ascending aorta, with or without regurgitation, and involving at least the sinuses of Valsalva
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Dissection of the ascending aorta
Minor cardiovascular system criteria are as follows:
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Mitral valve prolapse, with or without regurgitation
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Dilatation of main pulmonary artery in the absence of valvular or peripheral pulmonic stenosis or any other obvious cause in patients younger than 40 years
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Calcification of the mitral valve anulus in patients younger than 40 years
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Dilatation or dissection of the descending thoracic or abdominal aorta in patients younger than 50 years
Pulmonary system
For pulmonary system involvement to be considered diagnostic criteria, one of the minor criteria must be present. [25]
No major pulmonary system criteria exist.
Minor pulmonary system criteria are as follows:
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Apical blebs
Skin and integument
For skin and integument involvement to be considered diagnostic criteria, the major criteria or one of the minor criteria must be present.
The major skin and integument criterion is lumbosacral dural ectasia, as depicted by computed tomography (CT) or magnetic resonance imaging (MRI).
The minor skin and integument criteria are as follows:
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Striae atrophicae that are not associated with pregnancy or repetitive stress
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Recurrent or incisional hernia
Family history
For the family history to be considered contributory to a diagnosis of MFS, one of the major criteria must be present.
The major family history criterion is a parent, child, or sibling who meets the following diagnostic criteria independently:
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Presence of a mutation in FBN1 known to cause MFS
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Presence of a haplotype around FBN1, inherited by descent that is known to be associated with unequivocally diagnosed MFS in the family
No minor family history criteria exist.
Requirements for a diagnosis of MFS
Requirements for a diagnosis of MFS include the following:
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Index case – Major criteria in at least two different organ systems and involvement in a third organ system
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Family member – Presence of a major criterion in the family history, one major criterion in an organ system, and involvement of a second organ system
Revised (2010) Ghent criteria
In the 2010 revised Ghent nosology for MFS, [20, 23] diagnosis of the syndrome is based on seven rules. [22] In the absence of a family history, the following four criteria lead to the diagnosis of MFS:
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Aortic root dilatation Z score of 2 or greater and ectopia lentis
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Aortic root dilatation Z score of 2 or greater and identified FBN1 mutation
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Aortic root dilatation Z score of 2 or greater and systemic score of 7 or greater
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Ectopia lentis and FBN1 mutation with known aortic root dilatation
In the presence of a family history, the following three criteria lead to the diagnosis of MFS:
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Ectopia lentis and family history of MFS (as defined by rules 1-4)
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Systemic score of 7 or greater and family history of MFS (as defined by rules 1-4)
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Aortic root dilatation score of 2 or greater (in those aged ≥20 years) or 3 or greater (in those aged < 20 years) and family history of MFS (as defined by rules 1-4)
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Adult with Marfan syndrome. Note tall and thin build, disproportionately long arms and legs, and kyphoscoliosis.
