TABLE II.
Comparison of the Clinical findings in Patients with Aortopathy Due to Mutations in the TGFβ Signaling Pathway2
| Clinical syndrome (N, %) | ||||||
|---|---|---|---|---|---|---|
| Patient 1 (N=1) | Patient 2 and Aortopathy and Mitral valve dysfunction with JPS (N=5)1 | Aneurysm-Osteoarthritis syndrome (N=27)2 | Marfan syndrome (N=1,013)3 | Loeys-Dietz syndrome, I (N=40)4 | Loeys-Dietz syndrome, II (N=12)4 | |
| Associated Gene | SMAD4 (frameshifting indel) | SMAD4 (deletion) | SMAD3 | FBN1 | TGFBR1, TGFBR2 | TGFBR1, TGFBR2 |
| Clinical findings | ||||||
| Cardiovascular: | ||||||
| Aortic root dilation/dissection | 1/1 (100) | 4/6 (67)5 | 15/26 (58) | 775/1,013 (77)/ 145/1,013 (14) | 39/40 (98) | 12/12 (100) |
| Aneurysm other vessels | 0/1 (0) | 0/1 (0) | 7/17 (41) | unknown | 21/40 (52) | 8/11 (73) |
| Arterial tortuosity | 0/1 (0) | 0/1 (0) | 9/17 (53) | unknown | 21/25 (84) | 6/9 (67) |
| Mitral valve abnormalities (MVP/MR) | 1/1 (100) | 5/6 (83) | 13/22 (59) | 533/983(54)/ 313/959(33) | unknown | unknown |
| Congenital heart defects | 1/1 (100) | 1/6 (17) | 1/22 (5) | unknown | 9/40 (22) | unknown |
| Patent ductus arteriosus | 1/1 (100) | 0/6 (0) | 1/22 (5) | unknown | 14/40 (35) | unknown |
| Other heart diseases | 0/1 (0) | 0/6 (0) | 7/22 (32)6 | unknown | unknown | unknown |
| Musculoskeletal: | ||||||
| Pectus deformity | 0/1 (0) | 1/4 (25) | 3/19 (16) | 570/962 (59) | 27/40 (68) | unknown |
| Scoliosis | 0/1 (0) | 3/4 (75) | 9/21 (43) | 508/965 (53) | 20/40 (50) | unknown |
| Joint laxity (Beighton score >5) | 0/1 (0) | 3/4 (75) | 3/16 (19) | 600/956 (63) | 27/40 (68) | 12/12 (100) |
| Osteoarthritis (≥1 joint) | 0/1 (0) | 0/1 (0) | 21/21 (100) | unknown | unknown | unknown |
| Disc degeneration | 0/1 (0) | 0/1 (0) | 18/20 (900 | unknown | unknown | unknown |
| Craniofacial appearance: | ||||||
| Hypertelorism | 0/1 (0) | 0/1 (0) | 7/19 (37) | unknown | 36/40 (90) | 0/12 (0) |
| Abnormal palate/uvula | 0/1 (0) | 0/1 (0) | 11/19 (58) | unknown | 36/40 (90) | 3/12 (25) |
| Craniosynostosis | 0/1 (0) | 0/1 (0) | 0/27 (0) | unknown | 19/40 (48) | 0/12 (0) |
| Skin/Integument: | ||||||
| Velvety skin | 0/1 (0) | 0/1 (0) | 12/18 (67) | unknown | 11/40 (28) | 9/11 (82) |
| Striae | 0/1 (0) | 2/4 (50) | 11/18 (61) | 444/945 (47) | unknown | unknown |
| Umbilical/Inguinal hernia | 0/1 (0) | 0/1 (0) | 9/18 (50) | 96/988 (10) | unknown | 4/11 (36) |
| Ocular: | ||||||
| Ectopia lentis | 0/1 (0) | 0/4 (0) | 0/27 (0) | 542/1,013 (54) | 0/40 (0) | unknown |
| Myopia | 0/1 (0) | 1/4 (25) | unknown | 453/865 (52) | unknown | unknown |
| CNS: | ||||||
| CNS involvement | 0/1 (0) | 1/1 (100) | unknown | 154/1,013 (15) | unknown | unknown |
| Pulmonary: | ||||||
| Arteriovenous malformation | 1/1 (100) | 1/1 (100) | unknown | unknown | unknown | unknown |
1
A family with JPS, aortopathy and mitral valve dysfunction seqregating SMAD4 mutation [Andrabi et al., 2011];
2
Adapted from Table 2 [van de Laar et al., 2011];
3
Table 2 [Faivre et al., 2007];
4
Table 1 and 2 [Loeys et al., 2006];
5
Proband’s relatives have SMAD4 mutation with colonic polyps, mitral regurgitation, MVP and aortic dilation along with Marfan features.;
6
Left ventricular hypertrophy and atrial fibrillation; JPS, Juvenile polyposis syndrome, MVP, Mitral valve prolapse; MR, Mitral regurgitation