The prevalence of craniofacial and functional anomalies in TGF-β-opathies
| Craniofacial anomalies | LDS1 (TGFBR1) | LDS2 (TGFBR2) | LDS3 (SMAD3) | LDS4 (TGFB2 ligand) | LDS5 (TGFB3 ligand) | SGS (SKI) | Total | ||||||||
| n=15 | % | n=14 | % | n=3 | % | n=7 | % | n=1 | % | n=4 | % | n=44 | % | ||
| Face | |||||||||||||||
| 1 | Facial asymmetry | 13.3 | 5.0 | 35.7 | 0.0 | 0.0 | 1.0 | 14.3 | 0.0 | 0.0 | 0.0 | 0.0 | 8.0 | 18.2 | |
| 2 | Craniosynostosis | 2.0 | 13.3 | 4.0 | 28.6 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.0 | 100.0 | 10.0 | 22.7 |
| 3 | Broad forehead | 7.0 | 46.7 | 10.0 | 71.4 | 0.0 | 0.0 | 4.0 | 57.1 | 0.0 | 0.0 | 3.0 | 75.0 | 24.0 | 54.5 |
| 4 | Flat midface projection/infraorbital flatness | 13.0 | 86.7 | 14.0 | 100.0 | 2.0 | 66.7 | 3.0 | 42.9 | 1.0 | 100.0 | 4.0 | 100.0 | 37.0 | 84.1 |
| 5 | Mandibular hypoplasia/retrognathic mandible | 14.0 | 93.3 | 13.0 | 92.9 | 2.0 | 66.7 | 4.0 | 57.1 | 0.0 | 0.0 | 4.0 | 100.0 | 37.0 | 84.1 |
| 6 | Cleft palate/bifid uvula | 6.0 | 40.0 | 10.0 | 71.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 25.0 | 17.0 | 38.6 |
| Eyes | |||||||||||||||
| 7 | Abnormal eye shape/downslanting palpebral fissures | 11.0 | 73.3 | 10.0 | 71.4 | 1.0 | 33.3 | 6.0 | 85.7 | 0.0 | 0.0 | 4.0 | 100.0 | 32.0 | 72.7 |
| 8 | Hypertelorism | 5.0 | 33.3 | 7.0 | 50.0 | 0.0 | 0.0 | 2.0 | 28.6 | 0.0 | 0.0 | 4.0 | 100.0 | 18.0 | 40.9 |
| 9 | Telecanthus | 1.0 | 6.7 | 6.0 | 42.9 | 0.0 | 0.0 | 1.0 | 14.3 | 0.0 | 0.0 | 4.0 | 100.0 | 12.0 | 27.3 |
| 10 | Vertical dystopia | 5.0 | 33.3 | 7.0 | 50.0 | 0.0 | 0.0 | 3.0 | 42.9 | 1.0 | 100.0 | 3.0 | 75.0 | 19.0 | 43.2 |
| 11 | Exopthalmos | 3.0 | 20.0 | 6.0 | 42.9 | 0.0 | 0.0 | 1.0 | 14.3 | 0.0 | 0.0 | 4.0 | 100.0 | 14.0 | 31.8 |
| 12 | Blue sclera | 6.0 | 40.0 | 4.0 | 28.6 | 1.0 | 33.3 | 1.0 | 14.3 | 0.0 | 0.0 | 3.0 | 75.0 | 15.0 | 34.1 |
| 13 | Scleral show | 10.0 | 66.7 | 8.0 | 57.1 | 1.0 | 33.3 | 3.0 | 42.9 | 1.0 | 100.0 | 4.0 | 100.0 | 27.0 | 61.4 |
| 14 | Blepharoptosis | 11.0 | 73.3 | 9.0 | 64.3 | 2.0 | 66.7 | 4.0 | 57.1 | 0.0 | 0.0 | 3.0 | 75.0 | 29.0 | 65.9 |
| Nose | |||||||||||||||
| 15 | Slit nares/bulbous tip | 10.0 | 66.7 | 8.0 | 57.1 | 3.0 | 100.0 | 5.0 | 71.4 | 0.0 | 0.0 | 3.0 | 75.0 | 29.0 | 65.9 |
| Lips | |||||||||||||||
| 16 | Abnormal lip shape (thin upper lip vermillion, indistinct philtrum) | 9.0 | 60.0 | 9.0 | 64.3 | 2.0 | 66.7 | 4.0 | 57.1 | 0.0 | 0.0 | 4.0 | 100.0 | 28.0 | 63.6 |
| Ears | |||||||||||||||
| 17 | Low-set ears | 11.0 | 73.3 | 10.0 | 71.4 | 3.0 | 100.0 | 4.0 | 57.1 | 0.0 | 0.0 | 4.0 | 100.0 | 32.0 | 72.7 |
| 18 | Abnormal ear size | 4.0 | 26.7 | 3.0 | 21.4 | 0.0 | 0.0 | 1.0 | 14.3 | 0.0 | 0.0 | 3.0 | 75.0 | 11.0 | 25.0 |
| Skin | |||||||||||||||
| 19 | Skin translucency/nasal dorsal vein | 9.0 | 60.0 | 8.0 | 57.1 | 2.0 | 66.7 | 3.0 | 42.9 | 0.0 | 0.0 | 4.0 | 100.0 | 26.0 | 59.1 |
| Functional anomalies | |||||||||||||||
| 20 | Hearing deficiency | 6.0 | 40.0 | 2.0 | 14.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.0 | 18.2 |
| 21 | TMD | 7.0 | 46.7 | 6.0 | 42.9 | 1.0 | 33.3 | 1.0 | 14.3 | 1.0 | 100.0 | 1.0 | 25.0 | 17.0 | 38.6 |
| Limited ROM | 0.0 | 0.0 | 1.0 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 2.3 | |
| Deviation | 2.0 | 13.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 25.0 | 3.0 | 6.8 | |
| Sounds | 5.0 | 33.3 | 5.0 | 35.7 | 1.0 | 33.3 | 1.0 | 14.3 | 1.0 | 100.0 | 1.0 | 25.0 | 14.0 | 31.8 | |
| Arthralgia/patient-reported pain | 4.0 | 26.7 | 2.0 | 14.3 | 1.0 | 33.3 | 1.0 | 14.3 | 1.0 | 100.0 | 1.0 | 25.0 | 10.0 | 22.7 | |
| 22 | OSA | 4.0 | 26.7 | 2.0 | 14.3 | 0.0 | 0.0 | 1.0 | 14.3 | 0.0 | 0.0 | 3.0 | 75.0 | 10.0 | 22.7 |
| 23 | Snoring | 6.0 | 40.0 | 4.0 | 28.6 | 1.0 | 33.3 | 3.0 | 42.9 | 0.0 | 0.0 | 3.0 | 75.0 | 17.0 | 38.6 |
| 24 | Nystagmus/strabismus | 7.0 | 46.7 | 8.0 | 57.1 | 0.0 | 0.0 | 2.0 | 28.6 | 1.0 | 100.0 | 1.0 | 25.0 | 19.0 | 43.2 |
| CAI average scores | 11.3 | 12.4 | 7.0 | 8.1 | 5.0 | 18.0 | 11.3 | ||||||||
Percentages over 50% are in bold numbers. To calculate the Craniofacial Anomalies Index (CAI), 1 point is granted for the presence of each of the following characteristics for each patient. A total achievable score is 24. The average CAI per subtype is provided.
LDS, Loeys-Dietz syndrome; OSA, obstructive sleep apnoea; ROM, range of motion; SGS, Shprintzen-Goldberg syndrome; SMAD3, signal transducer in TGF-β; TGF-β, transforming growth factor-beta; TGFB2, TGF-β 2; TGFB3, TGF-β 3; TGFBR1, TGF-β receptor 1; TGFBR2, TGF-β receptor 2; TMD, temporomandibular disorder.