Table 4.
Comparison of the diagnostic criteria of MFS according to the Berlin versus Ghent-1 nosology
| Berlin nosology | Ghent-1 nosology |
|---|---|
| Skeletal manifestations | Skeletal system – major criterion (≥4 of the major criteria from the following list): |
| Anterior chest deformity, especially asymmetric pectus excavatum/carinatum | Pectus carinatum Pectus excavatum that requires surgery |
| Dolichostenomelia not due to scoliosis or tall stature, especially when compared to unaffected first-degree relatives | Upper-to-lower-segment ratio <0.85 or arm span-to-height ratio >1.05 |
| Arachnodactyly | Positive wrist and thumb sign Medial displacement of the medial malleolus causing pes planus |
| Vertebral column deformity: scoliosis; thoracic lordosis; or reduced thoracic kyphosis | Scoliosis >20° or spondylolisthesis Extension at elbows <170° |
| Protrusio acetabulae | Protrusio acetabuli of any degree Skeletal system – minor criteria (skeletal involvement with two of the major criteria or one of the major and two of the minor criteria) Pectus excavatum not requiring surgery |
| Abnormal appendicular joint mobility: congenital flexion contractures; hypermobility | Joint hypermobility |
| High, narrowly arched palate and dental crowding | High-arched palate with crowding of teeth Facial features (3/5): dolichocephaly; enophthalmos; downslanting palpebral fissures; malar hypoplasia; retrognathia |
| Ocular manifestations | Ocular system – major criterion |
| Ectopia lentis* | Ectopia lentis of any degree Ocular system – minor criteria (ocular involvement with ≥2 minor criteria): |
| Flat cornea | Flat cornea |
| Elongated globe, retinal detachment, myopia | Increased axial length of the globe (>23.5 mm) Hypoplastic ciliary muscle causing decreased miosis |
| Cardiovascular manifestations | Cardiovascular system – major criteria |
| Dilatation of the ascending aorta* | Aneurysm of the ascending aorta involving at least the sinuses of Valsalva |
| Aortic dissection,* aortic regurgitation | Dissection of the ascending aorta Cardiovascular system – minor criteria (cardiovascular involvement with one major or ≥1 minor criterion) |
| Mitral regurgitation due to mitral valve prolapse, mitral valve prolapse | Mitral valve prolapse (irrespective of mitral regurgitation) Dilatation of the main pulmonary artery <40 years of age (unassociated with pulmonic stenosis) |
| Calcification of the mitral annulus | Calcification of the mitral annulus <40 years of age |
| Abdominal aortic aneurysm; dysrhythmia; endocarditis | Dilatation or dissection of the descending thoracic or abdominal aorta <50 years of age |
| Pulmonary manifestations | Pulmonary system – minor criteria (pulmonary involvement with ≥1 minor criteria) |
| Spontaneous pneumothorax | Spontaneous pneumothorax |
| Apical bleb | Apical blebs (radiography) |
| Skin and integument | Skin and integument – minor criteria (skin and integumental involvement with ≥1 minor criteria) |
| Striae distensae | Striae distensae |
| Inguinal hernia, other hernia (umbilical, diaphragmatic, incisional) | Recurrent or incisional hernia |
| Central nervous system manifestations | Dura: major criterion |
| Dural ectasia,* lumbosacral meningocele, dilated cisterna magna, learning disability (verbal performance discrepancy), hyperactivity with or without attention deficit disorder | Lumbosacral dural ectasia |
| Genetics |
Family and genetic history (present with ≥1 major criterion) First-degree relative who independently meets the Marfan criteria |
| Autosomal dominant inheritance | Mutation in FBN1 known to cause MFS |
| 25%–30% of cases are sporadic; paternal age effect | Haplotype around the FBN1 locus inherited via descent and is unequivocally associated with a diagnosed Marfan in the family |
| Requirements for diagnosis | Requirements for diagnosis |
| In the absence of an unequivocally affected first-degree relative: involvement of the skeleton and at least two other systems; at least one major manifestation. In the presence of at least one unequivocally affected first-degree relative: involvement of at least two systems; at least one major manifestation preferred, but this will depend somewhat on the family’s phenotype. |
For the index case: if the family/genetic history is not contributory, then major criteria in at least two different organ systems and involvement of a third organ system. If a mutation known to cause MFS in others is detected, then one major criterion in an organ system and involvement of a second organ system. For a relative of an index case: the presence of a major criterion in the family history, as well as one major criterion in an organ system and involvement of a second organ system. |