Osteogenesis Imperfecta
Osteogenesis Imperfecta (OI) is a disorder of bone fragility caused generally by mutations in the COL1A1 and COL1A2 genes that encode type I collagen.
Overview
-
Osteogenesis Imperfecta (OI) is a disorder of bone fragility caused generally by mutations in the COL1A1 and COL1A2 genes that encode type I collagen. OI is one of the most common skeletal dysplasias. It is a generalized disease that is phenotypically and molecularly heterogeneous manifesting with a broad array of signs and symptoms including connective tissue and systemic manifestations in addition to bone fragility.
-
The more prevalent autosomal dominant forms of osteogenesis imperfecta are caused by primary defects in type 1 collagen, whereas autosomal recessive forms are caused by deficiency of proteins which interact with type 1 procollagen. There are at least 8 different types of the disease based on the inheritance. The differential diagnosis of OI includes child abuse, rickets, osteomalacia and other rare skeletal syndromes.
-
The Igenomix Osteogenesis Imperfecta Precision Panel can be used to make a directed and accurate differential diagnosis of bone fragility ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
The Igenomix Osteogenesis Imperfecta Precision Panel is indicated for those patients with a suspected clinical diagnosis of osteogenesis imperfecta presenting with the following manifestations:
- Blue sclerae
- Triangular facies
- Macrocephaly
- Hearing loss
- Defective dentition
- Barrel chest
- Scoliosis
- Limb deformities
- Pregnancy ultrasound: Limb-length abnormalities at 15-18 weeks’ gestation, decreased mineralization of calvaria, bowing of the long bones, multiple rib fractures
- Fractures
- Joint laxity
- Growth retardation
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team, encompassing physical rehabilitation and surgical procedures, management of hearing, dental and pulmonary abnormalities, as well as drugs, such as bisphosphonates and recombinant human growth hormone.
- Prenatal detection of osteogenesis imperfecta for a directed obstetric and perinatal treatment of affected infants.
- Combining phenotypic and genotypic data to improve diagnostic rate of these patients in the target population.
- Risk assessment of asymptomatic family members according to the mode of inheritance
Genes & Diseases
See all genes and diseases
|
GENE |
OMIM DISEASES |
INHERITANCE* |
% GENE COVERAGE (20X) |
HGMD** |
| ALPL | Adult Hypophosphatasia, Childhood Hypophosphatasia | AD,AR | 100% | 320 of 321 |
| ARCN1 | Rhizomelic Short Stature With Microcephaly, Micrognathia, And Developmental Delay | AD | 99.91% | 4 of 4 |
| B3GAT3 | Multiple Joint Dislocations, Short Stature, Craniofacial Dysmorphism With Or Without Congenital Heart Defects | AR | 99.86% | 15 of 15 |
| B4GALT7 | B4GALT7-Related Spondylodysplastic Ehlers-Danlos Syndrome | AR | 99.92% | 11 of 11 |
| BMP1 | Osteogenesis Imperfecta Type XIII | AR | 99.98% | 27 of 28 |
| CLCN5 | Dent Disease, X-linked Recessive Hypophosphatemic Rickets, Nephrolithiasis With Renal Failure, Low Molecular Weight Proteinuria With Hypercalciuria And Nephrocalcinosis | X,XR,G | 99.39% | NA of NA |
| COL1A1 | Arthrochalasia, Ehlers-Danlos Syndrome, Caffey Disease, Dermatofibrosarcoma Protuberans, Osteogenesis Imperfecta Type I, IIA, III, IV | AD | 99.98% | 1156 of 1159 |
| COL1A2 | Arthrochalasia Ehlers-Danlos Syndrome, Cardiac-Valvular Ehlers-danlos Syndrome, Osteogenesis Imperfecta Type IIA, III, IV, Osteoporosis | AD,AR | 100% | 576 of 581 |
| CREB3L1 | Osteogenesis Imperfecta Type XVI | AR | 99.98% | 4 of 4 |
| CRTAP | Osteogenesis Imperfecta Type VII | AR | 99.98% | 29 of 30 |
| FGF23 | Autosomal Dominant Hypophosphatemic Rickets, Familial Hyperphosphatemic Tumoral Calcinosis | AD,AR | 100% | 21 of 21 |
| FKBP10 | Bruck Syndrome, Kuskokwim Syndrome, Osteogenesis Imperfecta Type XI | AR | 100% | 51 of 51 |
| IFITM5 | Osteogenesis Imperfecta, Type V | AD | 100% | 4 of 4 |
| KDELR2 | Congenital Sucrase-Isomaltase Deficiency | 75.90% | NA of NA | |
| LRP5 | Autosomal Dominant Endosteal Hyperostosis, Exudative Vitreoretinopathy, Hyperostosis Corticalis Generalisata, Isolated Polycystic Liver Disease, Autosomal Dominant Osteopetrosis, Osteoporosis-Pseudoglioma Syndrome, Osteosclerosis-Developmental Delay-Craniosynostosis Syndrome, Retinopathy Of Prematurity, Van Buchem Disease Type 2 | AD,AR | 98.12% | 265 of 269 |
| MBTPS2 | Bresek Syndrome, Ichthyosis Follicularis-Alopecia-Photophobia Syndrome, Keratosis Follicularis Spinulosa Decalvans, X-linked Mutilating Palmoplantar Keratoderma With Periorificial Keratotic Plaques, Osteogenesis Imperfecta Type XIX, X-linked Mutilating Palmoplantar Keratoderma With Periorificial Keratoticplaques | X,XR,G | 100% | NA of NA |
| MESD | Osteogenesis Imperfecta Type XX | AR | 99.89% | NA of NA |
| P3H1 | Osteogenesis Imperfecta Type VIII | AR | 94.60% | NA of NA |
| PHEX | X-linked Dominant Hypophosphatemic Rickets | X,XD,G | 99.42% | NA of NA |
| PLOD2 | Bruck Syndrome | AR | 99.97% | 29 of 29 |
| PLS3 | Bone Mineral Density Quantitative Trait Locus | X,XD,G | 95.54% | NA of NA |
| PPIB | Osteogenesis Imperfecta Type IX | AR | 100% | 14 of 14 |
| SEC24D | Cole-Carpenter Syndrome | AR | 99.97% | 14 of 14 |
| SERPINF1 | Osteogenesis Imperfecta Type VI | AR | 99.73% | 42 of 46 |
| SERPINH1 | Osteogenesis Imperfecta Type X, Preterm Premature Rupture Of The Membranes | AR,MU,P | 100% | 9 of 10 |
| SGMS2 | Calvarial Doughnut Lesions With Bone Fragility | AD | 99.93% | 3 of 3 |
| SLC34A3 | Hereditary Hypophosphatemic Rickets With Hypercalciuria, Hereditary Hypophosphatemic Rickets With Hypercalciuria | AR | 100% | 52 of 52 |
| SP7 | Osteogenesis Imperfecta Type XII | AR | 99.98% | 3 of 3 |
| SPARC | Osteogenesis Imperfecta Type XVII | AR | 100% | 4 of 4 |
| TENT5A | Osteogenesis Imperfecta Type XVIII | AR | 99.84% | NA of NA |
| TMEM38B | Osteogenesis Imperfecta Type XIV | AR | 99.99% | 5 of 6 |
| WNT1 | Idiopathic Juvenile Osteoporosis, Osteogenesis Imperfecta Type XV | AR | 99.84% | 57 of 59 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
Pauli, R. (2019). Achondroplasia: a comprehensive clinical review. Orphanet Journal Of Rare Diseases, 14(1). doi: 10.1186/s13023-018-0972-6
Horton, W., Hall, J., & Hecht, J. (2007). Achondroplasia. The Lancet, 370(9582), 162-172. doi: 10.1016/s0140-6736(07)61090-3
Baitner, A., Maurer, S., Gruen, M., & Di Cesare, P. (2000). The Genetic Basis of the Osteochondrodysplasias. Journal Of Pediatric Orthopaedics, 594-605. doi: 10.1097/00004694-200009000-00010
Ornitz, D. M., & Legeai-Mallet, L. (2017). Achondroplasia: Development, pathogenesis, and therapy. Developmental dynamics : an official publication of the American Association of Anatomists, 246(4), 291–309. https://doi.org/10.1002/dvdy.24479
Daugherty A. (2017). Achondroplasia: Etiology, Clinical Presentation, and Management. Neonatal network : NN, 36(6), 337–342. https://doi.org/10.1891/0730-0832.36.6.337
Horton, W., Hall, J., & Hecht, J. (2007). Achondroplasia. The Lancet, 370(9582), 162-172. doi: 10.1016/s0140-6736(07)61090-3
Legare JM. Achondroplasia. 1998 Oct 12 [Updated 2020 Aug 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/
