Clinical features of patients with SMAD2 variants
| p.Asn205* Family 1 II-1 III-1 | p.Ala278Val(*) | p.Asn318Lys Family 2 II-2 III-1 | p.Asn361Thr Family 4 III-2 | p.Gln388Arg(†) P3-1 P3-2 | p.Ser397Tyr Family 3 III–2 IV-2 II-2 II-3 | p.Leu449Ser(†) P1–1 | p.Gly457Arg(†) P2–1 | p.Ser467Leu Family 5 II–5 | Total n=15 | |||||||
| Gender | M | M | M | F | F | M | F | F | M | F | F | F | F | F | M | M/F: 6/9 |
| Age at diagnosis (years) | 70 | 30 | 51 | 65 | 30 | 53 | 54 | 59 | 44 | 9 | 64 | 51 | 47 | 17 | 64 | |
| Arterial anomalies | ||||||||||||||||
| Thoracic aortic aneurysm | + | + | + | + | + | – | + | + | + | – | – | – | – | + | + | 10 |
| Abdominal aortic aneurysm | – | – | + | – | – | – | – | – | – | – | – | – | – | – | – | 1 |
| Aneurysm cerebral arteries | NA | NA | NA | – | – | – | – | – | + | – | – | + | + | NA | NA | 3 |
| Arterial tortuosity of cerebral arteries | NA | NA | NA | – | – | + | – | NA | + | + | – | – | – | NA | NA | 3 |
| Coronary artery dissection | NA | NA | NA | – | – | + | – | – | – | – | – | – | – | – | – | 1 |
| Iliac artery abnormalities | NA | NA | NA | – | – | + | – | – | – | – | – | – | – | – | – | 1 |
| Valve abnormalities (M, A, T, U) | NA | NA | NA | +AT | +A | – | +M | – | – | – | – | NA | +U | – | +M | 5 |
| Joint anomalies | ||||||||||||||||
| Arthritis | NA | NA | NA | + | + | + | + | + | – | – | + | + | NA | + | NA | 8 |
| Painful joints | NA | NA | NA | – | – | + | + | + | – | – | + | + | + | + | NA | 7 |
| Disc degeneration | NA | NA | + | NA | NA | NA | + | + | NA | NA | NA | NA | NA | + | NA | 4 |
| Skeletal anomalies | ||||||||||||||||
| Pes planus | NA | NA | NA | – | – | + | – | – | – | NA | NA | – | + | + | – | 3 |
| Scoliosis | NA | NA | NA | + | + | + | – | – | – | – | – | – | – | + | + | 5 |
| Pectus deformity | NA | NA | NA | + | – | – | – | – | – | – | – | – | – | + | + | 3 |
| Long fingers | + | + | NA | + | + | – | – | – | – | – | – | – | + | + | – | 6 |
| Tall stature | + | + | NA | + | + | – | – | – | + | NA | – | – | – | + | – | 6 |
| Skin anomalies | ||||||||||||||||
| Striae | NA | NA | NA | NA | NA | NA | + | + | + | – | – | – | – | – | – | 3 |
| Hernia D/I/U | NA | NA | NA | +D | +I | +I | +A | – | – | – | +D | – | – | +I | +I | 7 |
| Skin translucency | NA | NA | NA | NA | NA | NA | – | – | – | – | + | – | – | – | – | 1 |
| Skin hyperelasticity | NA | NA | NA | NA | NA | NA | NA | NA | – | – | + | – | NA | – | – | 1 |
| Easy bruising | NA | NA | NA | NA | NA | NA | – | + | + | – | + | + | – | – | + | 5 |
| Craniofacial anomalies | ||||||||||||||||
| Hypertelorism | – | – | – | + | – | – | – | – | + | + | + | – | – | – | – | 4 |
| Abnormal palate | – | – | + | + | – | – | + | + | + | – | – | – | – | + | – | 6 |
| Abnormal uvula | – | – | – | + | – | + | – | – | – | – | – | – | – | – | – | 2 |
| Downslanting palpebral fissures | – | – | – | + | – | + | NA | NA | – | – | – | – | NA | + | – | 3 |
| Dolichocephaly | – | – | + | + | – | – | – | – | – | – | + | – | – | + | – | 4 |
| Other phenotypic anomalies | ||||||||||||||||
| Transient ischaemic attacks | – | – | NA | NA | NA | NA | – | – | – | – | – | – | + | – | NA | 1 |
| Migraine | NA | NA | NA | – | + | NA | + | – | + | – | – | + | + | – | NA | 5 |
| Spontaneous pneumothorax | – | – | NA | – | – | NA | – | – | – | – | – | – | + | – | – | 1 |
| Varices | NA | NA | NA | – | – | + | – | + | – | – | + | + | – | – | – | 4 |
Valve abnormalities: M, mitral valve; A, aortic valve; T, tricuspid valve; U, unspecified. Hernia: D, diaphragmatic; I, inguinalis; U, umbilicalis; A, abdominal wall.
(*) and (†) represent (likely) pathogenic variants previously identified in SMAD2 by Zhang et al20 and Micha et al,19 respectively.
+, present; −,absent.
F, female; M, male; NA, not available.