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
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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/
