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
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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.
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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.
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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
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/