Osteogenesis Imperfecta (OI)
OI is a genetically heterogenous disorder characterized primarily by fractures. About 90% of affected individuals have mutations in type I collagen genes (COL1A1 and COL1A2) and in these families the condition is a dominantly inherited disorder. Some of the remainder have mutations in one of two other genes (CRTAP and LEPRE1). In these families, OI is recessively inherited.
As there are two laboratory techniques for identifying OI, the clinical circumstances may dictate your approach to testing. This listing of the clinical presentation of OI may help in this determination. Clinicians may also want to read FAQs about OI v non-accidental injury.
OI TABLE: Clinical Classification of Osteogenesis Imperfecta
| OI type | Clinical Presentation | Inheritance | Biochemical | Gene |
| I | Fractures, normal stature, little or no deformity, blue sclerae, hearing loss | AD | 50% reduction in type I collagen synthesis | COL1A1 |
| II | Lethal in neonatal period; multiple fractures, minimal clavarial mineralization, beaded ribs, compressed femurs, long bone deformity and platyspondyly. | AD | Structural alteration in type I collagen chains; overmodification | COL1A1 or COL1A2 |
| III | Multiple fractures, progressively deforming bones, moderate deformity at birth, sclerael hue varies, dentinogenesis imperfecta (DI), hearing loss (HL), very short. | AD | Structural alteration in type I collagen chains; overmodification | COL1A1 or COL1A2 |
| IV | Multiple fractures, normal sclerae in adults, mild/moderate deformity, variable short stature, DI, some HL. | AD | Structural alteration in type I collagen chains; overmodification | COL1A1 or COL1A2 |
| V | Similar to OI IV plus hyperplastic callus formation, calcif. of interosseous membrane of forearm, anterior radial head dislocation. (Glorieux et al 2001) | AD | Normal | Unknown |
| VI | Similar to OI IV plus early onset vertebral compression fractures, mineralization defect, no DI (Glorieux 2002) | Normal | Unknown | |
| VII | OI type II or III phenotype plus rhizomelic shortening and significant bowing. Loss of function mutations c/w OI type II. (Morello R et al 2007) | AR | Structural alteration in type I collagen chains; overmodification | CRTAP |
| VIII | OI type II or III phenotype plus gracile undermineralized bone and bulbous epiphyses. (Cabral WA et al 2007) | AR | Structural alteration in type I collagen chains; overmodification | LEPRE1 |
References:
Byers PH The Metabolic & Molecular Basis of Inherited Disease 8th Edition Volume IV 2000 Disorders of Collagen Biosynthesis and Structure p 5241-85.Byers PH et al. Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet. 1988 Feb;42(2):237-48.
Sillence DO et al. Genetic heterogeneity in osteogenesis imperfecta J Med Genet 1979 Apr;16(2):101-16.
Wenstrup RJ et al. Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta. Am J Hum Genet. 1990 May;46(5):975-82.
Glorieux FH et al. Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res 2000 Sep;15(9):1650.
Glorieux FH et al. Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res 2002 Jan;17(1):30-8.
Prenatal Diagnosis and Mode of Delivery:
Pepin M et al. Strategies and outcomes of prenatal diagnosis for osteogenesis imperfecta: a review of biochemical and molecular studies completed in 129 pregnancies. Prenat Diagn. 1997 Jun;17(6):559-70.
Cubert R et al. Osteogenesis imperfecta: mode of delivery and neonatal outcome. Obstet Gynecol. 2001 Jan;97(1):66-9.
CRTAP & LEPRE1 References:
Morello, R et al Cell 2006 Oct 20;127(2):291-304. CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta.
Barnes AM et al NEJM 2006 Dec 28;355(26):2757-64. Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.
Cabral WA et al Nat Genet Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. 2007 Mar;39(3):359-65.