Table 1.
Clinical features according to the revised Ghent nosology for Marfan syndrome1 for the five probands with a FBN1 mosaic pathogenic variant from this report and for the two symptomatic mosaic patients from the literature.
| Patient 1 (present study) | Patient 2 (present study) | Patient 3 (present study) | Patient 4 (present study) | Patient 5 (present study) | Blyth et al.11 | Rekondo et al.12 | |
|---|---|---|---|---|---|---|---|
| FBN1 mosaic pathogenic variant |
c.3037G>A p.(Gly1013Arg) |
c.3208+2T>A |
c.3221G>A p.(Cys1074Tyr) |
c.4139G>A p.(Cys1380Tyr) |
c.5546-750_6163+1205del (exons 45-49 deletion) |
Exons 13–49 deletion | c.2677+5G>C |
| Age at diagnosis | 8 | 3 | 6 | 48 | 5 | 3 | 49 |
| Age at consultation | 23 | 53 | 28 | 48 | 26 | 5 | 58 |
| Cardiovascular | |||||||
| Ascending aortic dilatation | Y | Y | N | Y | Y | N | NA |
| Valsalva diameter (z score (Campens et al.14) | 44 mm (+3.8 SD) | 48 mm (+3.4 SD) | 32 mm (+1 SD) | 45 mm (+2.7 SD) | 43 mm (+3.1 SD) | NA | NA |
| Ascending aortic dissection | N | N | N | Y | N | N | N |
| Aortic surgery | N | N | N | Y | N | N | Y |
| Age/type/indication of surgery | N | N | N | 48/Bentall/type A aortic dissection | N | N | 49/percutaneous placement of an endovascular prosthesis/type B aortic dissection |
| Mitral valve prolapse | N | N | N | N | Y | Y | NA |
| Ascending aortic dilatation or dissection before 40 years old | N | N | N | N | N | N | N |
| Ocular | |||||||
| Ectopia lentis | Y | Y | Y | N | Y | Y | N |
| Age at ectopia lentis diagnosis | 8 | 3 | 6 | N | 11 | 3 | NA |
| Myopia (>3 dioptries) | Y | N | N | N | Y | Y | Y |
| Flat cornea | Y | Y | Y | N | Y | NA | NA |
| Musculoskeletal | |||||||
| Pectus carinatum | N | N | N | N | Y | Y | N |
| Severe pectus excavatum | N | Y | N | N | N | N | Y |
| Dolichostenomelia = reduced US/LS AND increased arm/height AND no severe scoliosis | N | N | N | NA | N | N | NA |
| Positive wrist and thumb signs (arachnodactyly) | Y | N | Y | NA | Y | Y | NA |
| Positive wrist or thumb signs | N | Y | N | NA | N | N | NA |
| Scoliosis >20° or spondylolisthesis | N | Y | N | Y | N | Y | Y |
| Limited elbow extension <170° | Y | Y | Y | NA | N | NA | NA |
| Joint hypermobility | N | N | N | NA | Y | Y | NA |
| Protrusio acetabulae | N | N | N | N | Y | NA | NA |
| Hindfoot deformity | N | N | N | N | N | NA | NA |
| Plain pes planus | N | Y | Y | N | N | Y | NA |
| Typical facial appearance (3/5: dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia) | N | Dolichocephaly, downslanting palpebral fissures, malar hypoplasia | N | N | N | Dolichocephaly, malar hypoplasia | NA |
| Highly arched palate with crowding | N | Y | Y | Y | Y | Y | NA |
| Other | |||||||
| Pneumothorax | N | N | N | N | N | NA | NA |
| Striae | Y | N | Y | Y | N | NA | NA |
| Recurrent herniae | N | N | N | Y | Y | NA | NA |
| Dural ectasia | Y | Y | N | NA | Y | NA | NA |
| Systemic score | 8 | 7 | 6 | ≥2 | 9 | ≥8 | ≥3 |
Y yes, N no, NA not available, US/LS upper segment to lower segment.