Table 2.
Phenotypic features of the 15 individuals with biallelic pathogenic SCUBE3 variants included in the study.
| Individual |
F1S1 |
F1S2 |
F2S1 |
F2S2 |
F3S1 |
F3S2 |
F3S3 |
F4S1 |
F5S1 |
F5S2 |
F6S1 |
F7S1 |
F8S1 |
F9S1 |
F9S2 |
Total (%) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SCUBE3 variant/change | p.Cys97Trp | p.Ile815Thr | p.Arg573∗ | p.Val747Asp_fs∗46 | c.2599+2T>C | p.Arg282_ Cys322del | p.Ile815Thr | p.Gly204Asp | p.Arg929∗ | ||||||||
| Age | 19 y | 10 y | 22 y | 15 y | 39 y | 29 y | 25 y | 11.5 y | 11.6 y | 7.3 y | 16 m | 26 m | 12.8 y | 8 y | 22.5 y | ||
| Gender | F | F | M | M | F | F | M | M | M | F | F | M | M | M | F | ||
| Prenatal growth retardation (−2 SDS) | + | − | + | + | + | N/A | N/A | + | N/A | N/A | + | + | + | − | − | 8/11 (82) | |
| Postnatal growth retardation (−2 SDS) | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | 15/15 (100) | |
| DD/ID | − | − | − | − | − | − | − | − | − | − | − | + | − | − | + | 1/15 (7) | |
| Speech delay | − | − | − | − | − | − | − | − | − | − | − | + | − | − | + | 3/15 (20) | |
| Hypotonia | − | − | − | − | − | N/A | − | − | − | − | + | + | − | − | − | 2/14 (14) | |
| Craniofacial | |||||||||||||||||
| Microcephaly (−2 SDS) | − | − | + | + | + | N/A | − | + | + | + | + | N/A | + | − | + | 9/13 (69) | |
| Long/triangular face | + | + | + | + | + | + | + | + | + | + | + | N/A | + | + | + | 14/14 (100) | |
| High forehead | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | 15/15 (100) | |
| High nasal bridge | + | + | + | + | + | + | + | + | + | + | − | − | + | + | + | 13/15 (73) | |
| Long nose | + | + | + | + | + | + | + | + | + | + | − | − | + | + | + | 13/15 (87) | |
| Thick lips | + | + | − | + | − | − | − | + | − | − | + | + | + | − | − | 7/15 (47) | |
| Short chin | + | + | + | + | + | N/A | + | + | + | + | + | + | + | + | + | 14/14 (100) | |
| Pointed china | + | + | + | + | N/A | N/A | + | + | + | + | − | − | + | + | + | 11/13 (85) | |
| Pierre Robin sequence/cleft palate | − | CP | − | − | − | N/A | − | − | − | − | − | PRS | PRS | − | − | 3/14 (21) | |
| Dental anomalies | H,DC | H,ED, DC | DC | DC | DC | DC | O, DC | MD,ED,DC,ET | ED | ED | DC,MA | MA | DC | DC | O,DC, MA | 15/15 (100) | |
| Skeletal anomalies | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | 15/15 (100) | |
| Short hands/brachydactyly | + | + | + | + | + | + | − | + | + | − | − | + | + | + | + | 12/15 (80) | |
| Hip defects | NIW/CV | CV | NIW,CV | NIW, CV | NIW,AD | NIW | N/A | NIW,CV | CV | − | − | − | − | − | − | 9/14 (64) | |
| Thin/short long bones | + | + | N/A | N/A | − | N/A | N/A | + | + | + | − | − | + | − | − | 6/11 (54) | |
| Squared vertebrae | + | + | − | + | + | N/A | N/A | − | − | − | − | − | + | − | − | 5/13 (39) | |
| Abnormal cervical vertebrae | + | + | N/A | N/A | − | N/A | N/A | N/A | − | − | + | − | + | − | − | 4/10 (40) | |
| 11 pairs of ribs | + | + | − | − | + | N/A | N/A | − | − | − | − | − | + | − | − | 4/13 (31) | |
| Scoliosis | + | + | − | + | − | N/A | N/A | − | + | + | − | − | + | − | − | 6/13 (46) | |
| Joint abnormalities | +b | +b | − | − | N/A | N/A | N/A | − | N/A | N/A | +c | N/A | +c | +c | N/A | 5/8 (63) | |
| Hearing loss (conductive) | − | − | + | + | − | N/A | + | − | N/A | N/A | − | − | + | − | − | 4/12 (33) | |
| Cardiac defects | − | − | − | − | − | N/A | − | − | − | CA | ASD | PFO | − | − | ASD | 4/14 (29) | |
| Other defects | − | − | − | − | − | − | − | − | − | − | − | OD,TM, HS, ST | BCC | Ny, SBH | Ny, AST, SBH | ||
AD, acetabular dysplasia; ASD, atrial septal defect; AST, astigmatism; BCC, bilateral coronal synostosis; CA, cardiac arrhythmia (ventricular extrasystoles, atrioventricular block); CP, cleft palate; CV, coxa valga; DC, dental crowding; ED, enamel dysplasia/multiple caries; ET, ectopic teeth; H, hypodontia; HD, hip dislocation (bilateral); HS, hypospadias; MA, misalignment of incisor; MD, macrodontia; N/A, not assessed; NIW, narrow iliac wing; Ny, nystagmus; O, oligodontia; OD, oropharyngeal dysphagia; PFO, patent foramen ovale; PRS, Pierre Robin sequence; SBH, sparse brittle hair; ST, strabismus; TM, tracheo-bronchomalacia.
This feature becomes more evident at older ages.
Joint hypermobility.
Joint stiffness (F6S1); limited flexion of the proximal interphalangeal joints in both hands (F8S1); limited flexions of fingers, and hand grip difficulties (F9S1).