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Osteogenesis imperfecta (OI) is a group of heritable connective tissue disorders primarily affecting bone fragility due to defective synthesis of type I collagen.
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https://www.youtube.com/watch?v=uxm7aa89Ajk
OI Clinical nomenclature:
| OI clinical type | Description of severity |
|---|---|
| OI 1 | Non-deforming mild OI with blue sclera |
| OI 2 | Perinatal lethal form of OI |
| OI 3 | Severe, progressively deforming OI |
| OI 4 | Common variable OI with normal sclera |
| OI 5 | OI with progressive calcification abnormalities |
| Feature | Description |
|---|---|
| Genetic cause | Mutations in COL1A1 or COL1A2 genes (most common) |
| Inheritance | Autosomal dominant (common), also autosomal recessive forms |
| Defect | Type I collagen defect → weak, brittle bone matrix |
| Pathophysiology | Impaired osteoid formation and abnormal bone remodeling |
Sillence Classification:
| Type | Inheritance | Clinical Severity | Features |
|---|---|---|---|
| I | AD | Mild | Blue sclera, normal stature, fractures, no deformity |
| II | AD/AR | Perinatal lethal | Fractures in utero, crumpled bones, stillbirth |
| III | AR | Severe | Progressive deformities, short stature, fractures at birth |
| IV | AD | Moderate | Normal sclera, mild-to-moderate deformity |
| V–VIII | Various genes | Variable | Atypical features (e.g., calcified interosseous membranes, Bruck syndrome) |
OI clinical and genetic heterogeneity. OI clinical variability ranges from mild non-deforming OI to severe and lethal OI forms. Genetic diversity of the disorder is characterised by OI pathogenic variants in more than 22 different genes. Autosomal dominant (AD), autosomal recessive (AR) and X-linked recessive (XLR) inheritance patterns were observed among OI families. A – Autosomal chromosome; OI – Osteogenesis Imperfecta; X – X chromosome; Y – Y chromosome
Zhytnik, L., Simm, K., Salumets, A. et al. Reproductive options for families at risk of Osteogenesis Imperfecta: a review. Orphanet J Rare Dis 15, 128 (2020). https://doi.org/10.1186/s13023-020-01404-w
| Feature | Description |
|---|---|
| Multiple fractures | With minimal trauma; often first sign |
| Bone deformities | Bowing, limb shortening, scoliosis |
| ‣ (Type I) | Due to thin collagen in sclera |
| ‣ | Opalescent teeth, enamel loss, early tooth wear |
| Hearing loss | Due to ossicle fractures or ‣ (late childhood–adult) |
| Short stature | Especially in Types III and IV |
| Ligamentous laxity | May lead to hypermobility |
| ‣ | Accessory bones within cranial sutures |
Osteogenesis imperfecta type II (lethal):
(a) Patient ectoscopy: very short and deformed long bones; excess and wrinkled skin on a deformed face and neck; (b) non-ossification of the skull with transparent meninges; (c) extremely small thoracic cage; (d) typical babygram X-ray scan of a patient with a case of osteogenesis imperfecta type II
Savoldi AM, Villar MAM, Machado HN, Llerena Júnior JC. Fetal Skeletal Lethal Dysplasia: Case Report. Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics. 2017;39(10):576-582. doi:https://doi.org/10.1055/s-0037-1603943
Osteogenesis imperfecta type V:
Clinical characteristics of OI type V caused by the IFITM5 c.−14 C> T mutation. (A–C) Phenotypic diversity within individuals, and the characteristic facial features: wide set eyes, flat nose, thin lips, broad jaw, and short, wide forehead (F6IV2, F4III6, F4III9). (D) Hyperplastic callus (F3II1). (E) Dentinogenesis imperfecta (F7II1). (F) Large olecranon and coronoid process (F6IV2). (G) Saber-like deformity of lower limbs (F4III6). (H,I) Joint contracture involving knees and toes (F4IV2, F4III9). Written informed consent for the publication of these images were obtained.
Cao YJ, Wei Z, Zhang H, Zhang ZL. Expanding the Clinical Spectrum of Osteogenesis Imperfecta Type V: 13 Additional Patients and Review. Frontiers in Endocrinology. 2019;10. doi:https://doi.org/10.3389/fendo.2019.00375