Laboratory Studies
No specific laboratory test exists with which to make the diagnosis of Marfan syndrome (MFS).
Molecular genetic testing can be performed to assist in making the diagnosis of MFS in the following two clinical situations:
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First, if the specific FBN1 mutation is known in an individual diagnosed with MFS, this information can be applied to help diagnose family members
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Second, linkage analysis can be performed in families with several individuals who are affected with MFS to assess involvement in the remaining undiagnosed relatives
It is known that the FBN1 locus is associated with MFS; however, it is possible that other genes may cause a marfanoid habitus with phenotypic manifestations similar to those seen in MFS. [27] The role of molecular genetics testing in the sporadic case is minor. In general, the diagnosis is made on a clinical basis using the previously described Ghent criteria (see Presentation).
Imaging Studies
Skeletal system
Standard radiography
Hand radiographs may be taken to demonstrate the typical finding of arachnodactyly. Specifically, the metacarpal index can be calculated by measuring the ratio of the average length and width of the second through fourth metacarpals. A ratio of more than 8.8 in males and 9.9 in females is indicative of arachnodactyly. Camptodactyly can be associated with MFS; this abnormal flexion at the interphalangeal (IP) joint should be noted clinically and on standard radiographs.
Spine radiographs may demonstrate a variety of abnormalities. Many patients are affected by scoliosis. Posteroanterior (PA) and lateral radiographs of the spine demonstrate the severity of the scoliotic curve and any thoracic lordotic or thoracolumbar kyphotic deformity. Thoracic lordosis, if present, should be addressed, as it can restrict pulmonary function. Thoracic lordosis is also a contraindication to the use of bracing on a scoliosis that is present at a lower level. Vertebral height is typically greater than normal. Spondylolisthesis is more prevalent in MFS and usually occurs at L5-S1.
Anteroposterior (AP) radiographs of the pelvis may demonstrate protrusio acetabuli, which occurs frequently in MFS. This condition may be present and progressive during childhood until it becomes symptomatic after the patient reaches maturity. Developmental dislocation of the hip may also occur; this is likely due to the patient's overall ligamentous laxity. The dislocated or subluxed hip is easily visualized on the AP and frogleg lateral views in the pediatric patient.
Chest radiographs (PA and lateral) may demonstrate pectus excavatum or carinatum, which may be found in patients with MFS. The anterior chest deformity is most easily detected when the chest is tilted in the axial plane.
Foot radiographs (AP and lateral weightbearing views) may demonstrate pes planovalgus secondary to the ligamentous laxity that is found in patients with MFS.
Skull radiographs (AP and lateral) may demonstrate a high arched palate, increased skull height, and an enlarged frontal sinus.
Computed tomography
Axial computed tomography (CT) images of the hips can be taken in order to detect subtle protrusio acetabuli.
Magnetic resonance imaging
Axial magnetic resonance imaging (MRI) of the hip can also be taken to detect subtle protrusio acetabuli. Dural ectasia, which involves enlargement of the thecal sac that contains cerebrospinal fluid (especially common in the sacral region), can be identified on MRI.
Ocular system
Ultrasonography (US) of the globe may demonstrate megalocornea that occasionally occurs with MFS. The axial length of the cornea is increased (normal length in adults, < 1 cm).
Cardiovascular system
Once electrocardiography (ECG) shows abnormal findings in the patient with MFS, transesophageal echocardiography (TEE) or MRI is usually the next modality that is used to elucidate any clinically significant structural abnormalities.
To identify aortic root enlargement, either a cross-sectional echocardiogram in the parasternal long-axis view or a standard MRI should be performed. This enlargement typically occurs near the sinuses of Valsalva, although the ascending aorta and more distal aspect of the aorta may be involved (associated with a worse overall prognosis).
Once an echocardiogram or MRI is obtained, the patient's results can be compared with their body size with the use of nomograms that are appropriate for the patient's age. The following equation describes how the aortic root dimensions are obtained for comparison with normal levels:
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Aortic root dimension = 24(BSA)1/3 + 0.1(age) – 4.3
where BSA stands for body surface area.
Because the aortic root diameter typically does not change, the expected aortic root diameter (determined with the above equation) is then compared to the patient's actual aortic root dimensions as seen on either echocardiography or MRI. The normal ratio should approximate 1.0. If the ratio is greater than 1.18, the patient is likely undergoing aortic root enlargement with an increased likelihood of aortic valvular abnormalities and dissection.
In patients with MFS, the risk of developing aortic regurgitation is directly related to the overall size of the aortic root. In patients with roots that are less than 40 mm in diameter, the risk of developing aortic regurgitation is remote; however, in patients with roots greater than 60 mm, the aortic regurgitation is almost always present.
Mitral valve prolapse may also be detected via echocardiographic analysis. One study demonstrated a unique anatomic abnormality that was thought to be specific for MFS. These authors found that all visible chordae tendineae arose from the posterior left ventricular wall rather than from one of the major papillary muscles.
Because vascular dilation beyond the aortic root can be found in MFS, thoracoabdominal magnetic resonance angiography (MRA) may be useful by providing a complete assessment of the arterial system. [28]
Other Tests
Ocular system
A slit-lamp examination is performed with full pupillary dilatation in order to characterize lens abnormalities. The most worrisome finding is that of retinal detachment, which may herald the onset of blindness. Lens dislocation can be diagnosed and usually occurs in a superolateral direction, though other directions are possible. Iridodonesis (fluttering of the iris) is also a common finding with ectopia lentis. Open-angle glaucoma, severe myopia, and cataracts are more common in patients with MFS and can be diagnosed via slit-lamp examination as well.
Keratometry is a study of the radius of curvature of the cornea. In general, patients with MFS have flatter corneas, and increasing flatness is associated with ectopia lentis.
Cardiovascular system
ECG is useful because valvular abnormalities are common in MFS; atrial and ventricular electrical conduction abnormalities, as well as cardiomyopathy, may be present in some patients. ECG represents the best initial screening test for cardiac dysfunction in MFS because more than 80% of the patients have cardiac dysfunction over the course of their lives. Common findings on ECG include T-wave inversions (mitral valve prolapse) and the development of anterior electrical forces across the precordial leads (pectus excavatum or cardiomegaly with leftward heart shift).
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Adult with Marfan syndrome. Note tall and thin build, disproportionately long arms and legs, and kyphoscoliosis.
