TABLE 1.
Clinical and molecular findings of 23 patients in this study
| Family | 1 | 2 | 3 | 4 | 5 | 6 | |||
|---|---|---|---|---|---|---|---|---|---|
| Patient | #1 | #2 | #3 | #4 | #5 | #6 | #7 | #8 | #9 |
| Mother | Son | Mother | Daughter | Mother | Daughter | ||||
| Clinical suspicion | OI | OI | OI | OI | OI | OI | OI | OI | OI |
| Final diagnosis | OI type I | OI type I | OI type I | OI type I | OI unclassified | OI type I | OI type I | OI type I | OI unclassified |
| General | |||||||||
| Sex | F | F | F | M | F | F | F | F | M |
| Age (years) | 67 | 41 | 55 | 26 | 47 | 6 | 45 | 18 | 27 |
| Height (cm/SD) | 143/−0.6 | 160.8/+0.4 | 154.5/−0.5 | 173.5/+0.4 | 138.6/−3.7 | 111.4/−0.6 | 156.6/−0.3 | 157.5/0.0 | 152.8/−3.2 |
| Outcome | Deceased | Alive | Alive | Alive | Alive | Alive | Alive | Alive | Alive |
| Skeletal | |||||||||
| Multiple bone fractures | + | + | + | + | + | + | + | + | + |
| Frequency of fractures | 8 | 10 | 7 | 6 | >50 | 2 | 2 | 6 | 5 |
| Position of fractures | LB, PT, FM, PB, FB | PH, EL, PF | FM, TB, SC, EL, PF | AK, EL, WR | FM, PH, PF, EL, PT | FM | SC, PF | SK, HM, EL, PH, KN | CX, HM, PT |
| Dental abnormality | − | − | + | − | − | − | NA | − | − |
| Joint hypermobility | NA | + | − | − | − | − | − | + | − |
| Beighton score | 6 | 2 | 4 | 2 | 8 | ||||
| Recurrent joint dislocation | + | − | − | + | − | − | − | + | + |
| Congenital hip dislocation | − | − | − | − | − | − | − | − | NA |
| Joint contracture | − | − | − | − | + | − | − | − | NA |
| Long bone deformity | − | − | − | − | + | − | − | − | + |
| Spinal deformity | + | + | − | + | − | − | − | + | + |
| Congenital clubfoot | − | − | − | − | − | − | − | − | NA |
| Flat feet | NA | + | + | − | + | + | + | + | + |
| Ruptures of tendon, ligament, or muscle | − | − | − | − | − | − | + | + | + |
| Intramuscular bleeding | NA | − | − | − | − | − | − | − | − |
| Joint pain | NA | NA | − | − | NA | NA | NA | + | NA |
| DXA(vertebral:g/cm2) | 0.548 | 1.132 | 0.743 | 0.961 | 0.547 | 0.432 | 0.645 | 1.145 | 0.936 |
| T‐score | −4.8 | −0.2 | −2.9 | −1.0 | −4.8 | − | 82 (%YAM) | − | −2.1 |
| Z‐score | −3.4 | −0.2 | −2.2 | −1.0 | −4.7 | − | 0 | −2.1 | |
| Skin | |||||||||
| Hyperextensibility | NA | NA | − | − | − | − | + | − | − |
| Fragility | NA | NA | − | − | + | + | + | + | − |
| Atrophic scars | NA | NA | − | − | − | − | − | − | − |
| Translucency | NA | + | − | − | NA | NA | + | − | − |
| Soft doughy skin | NA | NA | + | − | + | + | NA | NA | − |
| Piezogenic papules | NA | NA | NA | NA | − | − | + | − | NA |
| Easy bruising | NA | NA | − | − | − | − | − | − | + |
| Eye and ear | |||||||||
| Blue sclerae | + | + | + | + | + | + | + | + | + |
| Retinal detachment | NA | − | − | − | − | − | − | − | − |
| Refractive errors | NA | Myopia | Myopia | Myopia | − | − | Myopia | Myopia | + |
| Hearing impairment | + | + | + | − | + | − | + | + | − |
| Cardiovascular | |||||||||
| Vascular dissection | Ascending aorta | − | − | − | − | NA | − | NA | − |
| Arterial aneurysm | Lt. MCA | Bil. ICA | Rt. ICA | − | − | NA | Rt. MCA | NA | − |
| Cardiac valve disorder | AR | − | − | NA | − | NA | − | NA | MR, TR |
| Renal disease | PKD | URA | NA | NA | NA | NA | NA | NA | − |
| Hypertension | + | − | − | NA | − | − | + | − | NA |
| Others | SAH due to MCA rupture | SAH due to ICA rupture | SAH due to ICA rupture | Coronary‐pulmonary artery fistula | |||||
| Variant | |||||||||
| COL1A1(PV: OI) | COL1A1(PV: OI) | COL1A1(PV: OI, C1ROD) | COL1A1(PV: OI) | COL1A1(UV) | COL1A1(UV) | ||||
| c.779G > A | c.2829 + 1G > A | c.1243C > T | c.769G > A | c.1679del | c.572G > T | ||||
| p.Gly260Asp | p.Arg415* | p.Gly257Arg | p.Gly560Valfs*20 | p.Gly191Val | |||||
| Exon 11 | Intron 39 | Exon 19 | Exon 11 | Exon 25 | Exon 7 | ||||
| Family | 7 | 8 | 9 | 10 | 11 | |||
|---|---|---|---|---|---|---|---|---|
| Patient | #10 | #11 | #12 | #13 | #14 | #15 | #16 | #17 |
| Mother | Daughter | Elder brother | Younger brother | Father | Daughter | |||
| Clinical suspicion | OI | OI | OI | OI | OI | OI | OI | OI |
| Final diagnosis | OI type I | OI unclassified | OI unclassified | OI type I | OI type I | OI type I | OI type I | OI type I |
| General | ||||||||
| Sex | F | F | F | F | M | F | M | F |
| Age (years) | 37 | 3 | 26 | 14 | 16 | 9 | 41 | 8 |
| Height (cm/SD) | 151/−1.2 | 86.3/−1.7 | 133.9/−4.3 | 148.4/−1.5 | 150.3/−3.3 | 122/−1.8 | 168.5/−0.5 | 124.8/−1.8 |
| Outcome | Alive | Alive | Alive | Alive | Alive | Alive | Alive | Alive |
| Skeletal | ||||||||
| Multiple bone fractures | + | − | + | + | + | + | + | − |
| Frequency of fractures | 5 | − | 12 | 5 | 5 | 2 | 5 | − |
| Position of fractures | RD, UL, FB | − | FM | TB, FB, EL, RD | TB, RD, UL, CB, PF | TB, HM | FM, PF | − |
| Dental abnormality | + | − | + | − | − | − | + | + |
| Joint hypermobility | − | − | + | + | − | − | − | − |
| Beighton score | 7 | 7 | 4 | 4 | ||||
| Recurrent joint dislocation | − | − | − | − | − | − | − | − |
| Congenital hip dislocation | − | − | − | − | − | − | − | − |
| Joint contracture | − | − | + | − | − | − | − | − |
| Long bone deformity | − | + | + | − | − | − | − | − |
| Spinal deformity | − | − | + | − | − | − | − | + |
| Congenital clubfoot | − | − | − | − | − | − | − | − |
| Flat feet | − | − | + | + | − | − | − | − |
| Ruptures of tendon, ligament, or muscle | − | − | − | − | − | − | − | − |
| Intramuscular bleeding | − | − | − | − | − | − | − | − |
| Joint pain | − | − | NA | − | − | − | − | − |
| DXA(vertebral:g/cm2) | NA | NA | 0.886 | 0.864 | 0.837 | 0.716 | 0.981 | 0.55 |
| T‐score | −1.9 | 80 (%YAM) | − | − | −0.9 | − | ||
| Z‐score | −1.5 | −1.7 | 0 | 0 | −0.9 | −1.5 | ||
| Skin | ||||||||
| Hyperextensibility | − | − | − | + | − | − | − | − |
| Fragility | − | − | − | − | − | − | − | − |
| Atrophic scars | − | − | − | − | − | − | − | − |
| Translucency | − | − | − | − | − | − | − | − |
| Soft doughy skin | − | − | − | + | − | − | − | − |
| Piezogenic papules | − | − | NA | NA | − | − | + | − |
| Easy bruising | + | − | − | − | − | − | − | − |
| Eye and ear | ||||||||
| Blue sclerae | + | + | + | + | + | + | + | + |
| Retinal detachment | − | − | NA | − | − | − | − | − |
| Refractive errors | − | − | Myopia | − | − | − | Myopia | NA |
| Hearing impairment | − | − | − | − | − | − | NA | − |
| Cardiovascular | ||||||||
| Vascular dissection | − | − | − | NA | − | − | − | NA |
| Arterial aneurysm | − | − | − | NA | − | − | − | NA |
| Cardiac valve disorder | − | − | − | NA | − | − | − | NA |
| Renal disease | − | − | NA | NA | − | − | Rt. renal cyst | NA |
| Hypertension | − | − | − | − | − | − | − | NA |
| Others | ||||||||
| Variant | ||||||||
| COL1A1(UV) | COL1A2(UV) | COL1A2(PV: OI) | COL1A2(PV: OI) | COL1A1(PV: OI) | ||||
| c.559del | c.1963G > C | c.693 + 1G > A | c.2314G > A | c.2362G > A | ||||
| p.Arg187Valfs*78 | p.Gly655Arg | p.Gly772Ser | p.Gly788Ser | |||||
| Exon 7 | Exon 32 | Intron 14 | Exon 38 | Exon 34 | ||||
| Family | 12 | 13 | 14 | 15 | ||
|---|---|---|---|---|---|---|
| Patient | #18 | #19 | #20 | #21 | #22 | #23 |
| Father | Daughter | Son | ||||
| Clinical suspicion | OI | aEDS | aEDS | cEDS | vEDS | vEDS or OI |
| Final diagnosis | C1ROD | C1ROD | C1ROD | cEDS | C1ROD | C1ROD |
| General | ||||||
| Sex | M | F | M | M | M | F |
| Age (years) | 34 | 4 | 2 | 18 | 47 | 45 |
| Height (cm/SD) | 163.2/−1.5 | 99.7/−0.9 | 85.2/0.0 | 143.8/−1.5 | 173/−0.1 | 135.5/−4.0 |
| Outcome | Alive | Alive | Alive | Alive | Alive | Alive |
| Skeletal | ||||||
| Multiple bone fractures | + | − | − | − | + | − |
| Frequency of fractures | 6 | − | − | − | 2 | 1 |
| Position of fractures | NA | − | − | − | EL | TB |
| Dental abnormality | − | − | − | − | − | − |
| Joint hypermobility | + | + | + | + | + | + |
| Beighton score | 9 | 9 | 8 | 6 | NA | NA |
| Recurrent joint dislocation | − | − | − | − | − | + |
| Congenital hip dislocation | − | + | − | − | − | − |
| Joint contracture | − | − | − | − | − | − |
| Long bone deformity | − | − | − | − | + | NA |
| Spinal deformity | − | + | NA | − | − | − |
| Congenital clubfoot | − | − | − | − | − | + |
| Flat feet | + | + | + | − | − | − |
| Ruptures of tendon, ligament, or muscle | − | − | − | − | − | − |
| Intramuscular bleeding | − | − | − | − | − | − |
| Joint pain | − | − | − | − | − | − |
| DXA(vertebral:g/cm2) | 1.048 | NA | NA | NA | 0.787 | 0.623 |
| T‐score | −0.5 | −0.8 | −3.5 | |||
| Z‐score | −0.5 | −0.8 | ||||
| Skin | ||||||
| Hyperextensibility | + | + | + | − | + | − |
| Fragility | − | − | − | − | + | + |
| Atrophic scars | − | − | − | + | − | − |
| Translucency | − | − | − | − | + | + |
| Soft doughy skin | − | + | + | + | + | + |
| Piezogenic papules | NA | + | + | − | NA | NA |
| Easy bruising | + | + | + | + | − | + |
| Eye and ear | ||||||
| Blue sclerae | + | + | + | − | + | + |
| Retinal detachment | − | − | NA | − | − | − |
| Refractive errors | Myopia | Myopia, astigmatism | NA | − | − | − |
| Hearing impairment | NA | − | − | − | − | NA |
| Cardiovascular | ||||||
| Vascular dissection | − | − | − | − | Bil. ICA | Bil. VA |
| Arterial aneurysm | − | − | − | − | − | AAA |
| Cardiac valve disorder | NA | − | − | − | − | − |
| Renal disease | NA | − | − | − | − | Lt. renal AVM |
| Hypertension | NA | NA | NA | − | − | NA |
| Others | Cerebral infarction | Lateral medullary infarction | ||||
| Variant | ||||||
| COL1A2(PV: OI, C1ROD) | COL1A1(PV: cEDS) | COL1A1(PV: OI) | COL1A1(UV) | |||
| c.432 + 4_432 + 7del | c.934C > T | c.658C > T | c.571G > T | |||
| p.Arg312Cys | p.Arg220* | p.Gly191Cys | ||||
| Intron 9 | Intron 14 | Exon 9 | Exon 7 | |||
Abbreviations: +, present; −, absent; AAA, abdominal aortic aneurysm; AK, ankle; AR, aortic valve regurgitation; AVM, arteriovenous malformation; Bil., bilateral; C1ROD, COL1‐related overlap disorder; CB, clavicle bone; CX, coxal bone; EL, elbow; F, female; FB, fibula; FM, femur; HM, humerus; ICA, inner carotid artery; KN, knee; LB, lumbar spine; Lt., left; M, male; MCA, middle cerebral artery; MR, mitral valve regurgitation; NA, not available; PB, pubis; PF, phalanx of foot; PH, phalanx of hand; PKD, polycystic kidney disease; PT, patella; PV, previously published variant; RD, radius; Rt., right; SAH, subarachnoidal hemorrhage; SC, scapula; SK, skull; TB, tibia; TR, tricuspid valve regurgitation; UL, ulna; URA, unilateral renal aplasia; UV, unpublished variant; VA, vertebral artery; WR, wrist; YAM, young adult mean.