Table 2.1–4 Diagnosis of Marfan syndrome according to the criteria of the revised Ghent classification (Loeys et al. 2010).
| A diagnosis of Marfan syndrome is made with the following findings: | |
| A No confirmed family history of Marfan syndrome: | |
| 1. Aortic root dilation (Z≥2) or aortic dissection and lens luxation1 | |
| 2. Aortic root dilation (Z≥2) or aortic dissection and FBN1 mutation | |
| 3. Aortic root dilation (Z≥2) or aortic dissection and systemic involvement (≥7 points)1 | |
| 4. Lens luxation and FBN1 mutation previously noted in an individual with aortic dilation | |
| B At least one relative meeting one of the four criteria above independently of the individual being examined (positive family history): | |
| 5. Positive family history and lens luxation | |
| 6. Positive family history and systemic involvement (≥7 points)1 | |
| 7. Positive family history and aortic root dilation (Z≥2 > 20 years, Z≥3≤20 years)1 | |
| C Systemic score2: | |
| Systemic characteristic: | Score points: |
| Positive wrist and thumb sign | 3 |
| Positive wrist or thumb sign | 1 |
| Pectus carinatum | 2 |
| Pectus excavatum or chest asymmetry | 1 |
| Talipes valgus | 2 |
| Pes planus | 1 |
| Pneumothorax | 2 |
| Dural ectasia | 2 |
| Otto disease (protrusio acetabuli) | 2 |
| Reduced leg-body ratio and arm length-height ratio > 1.05 (with exclusion of high-grade scoliosis)3 | 1 |
| Scoliosis or thoracolumbar kyphosis4 | 1 |
| Reduced elbow extension (170° or less) | 1 |
| Facial characteristics (at least three of the five signs)5 | 1 |
| Striae cutis distensae | 1 |
| Myopia > 3 diopter | 1 |
| Mitral valve prolapse | 1 |
1 Requires exclusion of relevant differential-diagnostic clinical signs of Shprintzen–Goldberg syndrome, Loeys–Dietz syndrome, or vascular Ehlers–Danlos syndrome and after TGFBR1/2 mutation analysis, collagen biochemistry examination and COL3A1 analysis if indicated (see Table 2.1-5).
2 Systemic involvement is present at ≥ 7 points (maximum 20).
3 The leg–body ratio, measured from the upper edge of the pubis, is considered abnormal from < 1 at an age of 0–5 years, < 0.95 at age 6–7, < 0.9 at age 8–9, and < 0.85 at age ≥ 10 in whites and < 0.78 in blacks.
4 Scoliosis is present with a Cobb angle ≥ 20° or a height difference between the right and left dorsal halves of the chest ≥ 1.5 cm when the patient is leaning forward.
5 Signs of facial dysmorphia are dolichocephalism, enophthalmos, laterally sloping eyelid axes, malar hypoplasia and retrognathism. Z = Aortic root Z score.
In our experience, there are many patients in whom it is not possible to diagnose a syndrome despite clear evidence of a genetically determined aortic disease. There are also patients who have nucleotide sequence changes in the “aortic genes” who do not have any manifestion of aortic disease. Substantial diagnostic difficulties may arise in children in particular, as many extra-aortic and cardiovascular changes have age-dependent manifestations. In addition, there are no established criteria for recording many signs of dysmorphia and assessing aortic changes, therefore clinical experience is vital. Due to multiple-organ involvement in many syndromes, collaboration between several medical disciplines is always essential. A third diagnostic rule should be that diagnostic assessment of patients with genetically determined aortic diseases should take place in specialized centers (von Kodolitsch et al. 2002). These centers are approved in Germany as part of “outpatient hospital treatment” (Book V, Para. 116b of the German Social Code) (Bekanntmachungen 2007). This regulation permits specialized hospitals to carry out comprehensive diagnosis, including gene sequencing, while approximately covering costs (Manow et al. 2010).
Table 2.1–5 Clinical signs relevant to the differential diagnosis in the revised Ghent classification (Loeys et al. 2010).
| Differential diagnosis | Gene | Clinical signs |
| Loeys–Dietz syndrome (LDS) | TGFBR1/2 | Cleft palate/bifid uvula, arterial tortuosity, hypertelorism, diffuse aortic and arterial aneurysms, craniosynostosis, talipes equinovarus, unstable cervical vertebrae, silky and brittle skin, bleeding tendency |
| Shprintzen–Goldberg syndrome (SGS) | FBN1 and others | Craniosynostosis, mental retardation |
| Congenital contractural arachnodactyly (CCA) | FBN2 | Wrinkled ears, contractures |
| Weill–Marchesani syndrome (WMS) | FBN1, ADAMTS10 | Microspherophakia, brachydactyly, stiff joints |
| Ectopia lentis syndrome (ELS) | FBN1, LTBP2, ADAMTSL4 | Exclusion of aortic dilation |
| Homocystinuria | CBS | Thromboses, mental retardation |
| Familial thoracic aortic aneurysm (FTAA)syndrome |
TGFBR1/2, ACTA2
|