Clinical features* | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient | Age | M/S | CVS | Ocular | DE | FH | minor | Diagnosis† | Exon | Mutation‡ | Predicted consequence‡ | Fibrillin-1 domain | Method of analysis |
*Clinical features. Musculoskeletal (M/S), cardiovascular (CVS), ocular and dural ectasia (DE) are marked with a + if features were found on examination that corresponded to major involvement by the Ghent criteria.3 The aortic root was considered dilated when the maximum diameter at the sinus of Valsalva exceeded published normograms for age and body surface area (95% normal confidence limits).39 AD indicates a previous aortic dissection. Dural ectasia was diagnosed based on published recommendations.40 + = DE present, - = DE absent, blank MRI scan not performed, D MRI declined (7 and 27), delayed (22 and 25) because of aortic root surgery or prevented because of spinal deformity (23), age (40), or lost to follow up (15), but all seven of these subjects would fulfil the Ghent criteria for MFS if dural ectasia were present. FH, family history. F, familial phenotype. S, sporadic phenotype. + indicates that at least one relative was examined and fulfilled the Ghent criteria independently. - indicates that the relatives were examined and did not fulfil the Ghent criteria independently. The number of systems where minor criteria (such as M/S features, mitral valve prolapse, striae, or pneumothorax) were found (excluding those systems which also had a major criterion) is indicated. Keratometry and ultrasound of the globe to look for minor opthalmological involvement was not performed routinely. | |||||||||||||
†Diagnosis. The diagnosis of MFS was made according to the Ghent criteria if there were at least two major criteria and minor involvement of a third system; -, third system involvement was not demonstrated in these subjects. FEL, familial ectopia lentis; EL ectopia lentis - sporadic; FTAA, familial thoracic aortic aneurysm; FMH, familial Marfan-like habitus; SG, Shprintzen-Goldberg syndrome based on features of fatal aortic dissection, craniosynostosis, joint laxity, and arthrogryposis multiplex congenita. Two subjects had just one minor Ghent criterion but were included because of the familial nature of mild Marfan features in case 35, where four subjects had minor musculoskeletal features of MFS, and the severity of the sporadic Marfan-like striae in subject 37. | |||||||||||||
‡Nucleic acid and amino acid numbering according to Pereira et al.5PTC, premature termination codon; Ins, insertion; Del, deletion. | |||||||||||||
§Published previously.23 | |||||||||||||
¶Published previously.24 | |||||||||||||
**FBN1 mutation also found in affected relatives. | |||||||||||||
††Reported previously.8 | |||||||||||||
‡‡Reported previously.9 | |||||||||||||
11 | 46 | - | + (AD) | - | + | F+ | 2 | MFS | 2 | G247+1A§** | Skip exon 2 | NH2 | CSGE |
3 | 45 | - | + | - | + | F+ | 2 | MFS | 8 | 932insT§** | PTC at 348 | cbEGF2 | CSGE |
7 | 65 | - | - | + | D | F- | 1 | FEL | 15 | C1879T** | R627C†† | cbEGF6 | DHPLC |
33 | 40 | - | + | - | + | F- | 2 | MFS | 15 | G1960A | D654N | TB2 | DHPLC |
36 | 54 | - | + (AD) | + | S | 2 | MFS | 18 | G2168-1A | Splice defect | cbEGF7 | DHPLC | |
40 | 9 | - | + | + | D | S | 0 | MFS− | 18 | G2243A | C748Y | cbEGF7 | CSGE |
21 | 38 | + | - | + | + | F+ | 0 | MFS | 20 | G2539+1A | Splice defect | cbEGF9 | DHPLC |
18 | 30 | - | + | - | + | F | 2 | MFS | 35 | 4365delCT§ | PTC at 1470 | cbEGF21 | CSGE |
17 | 31 | + | + | - | F | 1 | MFS | 36 | 4485delC§ | PTC at 1519 | cbEGF22 | CSGE | |
13 | 43 | - | + | + | F | 3 | MFS | 37 | C4621T§** | R1541X | TB4 | CSGE | |
14 | 31 | - | + | + | S | 2 | MFS | 44 | G5504A§ | C1835Y | cbEGF26 | CSGE | |
15 | 30 | - | + | + | D | S | 0 | MFS− | 45 | A5546-2G | Splice defect | cbEGF27 | DHPLC |
12 | 25 | + | + | + | F | 0 | MFS | 47 | G5788+1A¶ | Ins 33 bases | cbEGF29 | Sequencing | |
41 | 10 | - | + | + | S | 1 | MFS | 48 | T5929C | C1977R | cbEGF30 | CSGE | |
1 | 46 | - | + | + | + | F+ | 1 | MFS | 55 | G6773A§** | C2258Y | cbEGF 35 | CSGE |
2 | 43 | + | + | + | F- | 0 | MFS | 57 | A6998-2G** | Del 12 bases | TB7 | DHPLC | |
16 | 43 | - | + (AD) | + | S | 3 | MFS | 57 | C7180T§ | R2394X | TB7 | CSGE | |
26 | 37 | + | - | - | + | S | 1 | MFS | 59 | C7398A | Y2466X‡‡ | cbEGF38 | DHPLC |
24 | 52 | - | + | + | F | 2 | MFS | 59 | C7399T | Q2467X | cbEGF38 | DHPLC | |
42 | 40 | - | + | - | + | S | 2 | MFS | 62 | 7816insT | PTC at 2607 | cbEGF42 | CSGE |
27 | 17 | - | - | + | D | F- | 2 | FEL | 65 | T8339C** | L2780P | C-term | DHPLC |
29 | 55 | + | - | - | + | S | 2 | MFS | - | DHPLC | |||
30 | 25 | + | + | - | + | F | 0 | MFS | - | DHPLC | |||
5 | 62 | - | + | + | F+ | 1 | MFS | - | DHPLC | ||||
6 | 41 | + | + (AD) | - | + | F- | 0 | MFS | - | DHPLC | |||
19 | 48 | + | - | - | + | S | 1 | MFS | - | DHPLC | |||
34 | 50 | - | - | + | S | 0 | EL | - | DHPLC | ||||
22 | 38 | - | + | - | D | F | 2 | FTAA | - | DHPLC | |||
25 | 41 | - | + | - | D | F | 1 | FTAA | - | DHPLC | |||
23 | 48 | + | - | - | D | F- | 1 | FMH | - | DHPLC | |||
38 | 46 | - | - | - | + | F | 3 | MASS | - | DHPLC | |||
31 | 53 | - | - | - | - | F- | 3 | MASS | - | DHPLC | |||
37 | 32 | - | - | - | S | 1 | Striae | - | DHPLC | ||||
35 | 27 | - | - | - | F- | 1 | - | - | DHPLC | ||||
32 | 10 | - | + (AD) | - | S | 0 | SG | - | DHPLC |