Sillence classification of osteogenesis imperfecta
The original Sillence classification system grouped OI into four clinical categories of severity. A fifth phenotype was reported in 2000; hence, current nomenclature recognizes five types of OI (as well as a sixth category: OI, other types). Most forms can be classified clinically into mild, moderate, severe, and lethal.
Type I OI (mild): bone fragility, little or no deformity, normal stature, blue sclerae, osteopenia, and hearing loss in 50%, may (Type IA) or may not (Type IB) have dentinogenesis imperfecta. Mutation of COL1A1 or COL1A2 gene causing underproduction (50%) of normal type I collagen and subsequent hypomineralization. T scores are often –2.5 to –4.0. Inheritance is AD.
Type II OI (usually lethal): multiple in utero fractures and blue or gray sclerae, in utero /neonatal death common. Inheritance is AD or AR.
Type III OI (severe deforming): multiple fractures before 3 years, fractures heal with major skeletal deformities, triangular facies with frontal bossing, short stature, scoliosis, joint laxity, gray or blue sclerae, and hearing loss. Not usually ambulatory. Pulmonary insufficiency from thoracic deformity is a major cause of death before the age of 35 years. Usually results from a spontaneous mutation but can be AD or AR inheritance.
Type IV OI (moderate severity): variable short stature, variable bone fragility with a moderate number of fractures by the age of 10 years, wormian bones, normal (white) or gray sclerae, dentinogenesis imperfecta, some hearing loss, ambulatory. Inheritance is AD.
Type V OI (rare): similar to type IV but with hyperplastic callus formation post fracture (fracture risk moderate), normal sclera, limited pronation and supination at the forearm due to intramembranous bone formation. Mutation in IFITM5. Inheritance is AD.
The diagnosis of OI is primarily clinical. Several laboratories will perform collagen biochemical and molecular (DNA sequencing) analysis from a skin biopsy, and NextGen Sequencing from whole blood is available from some laboratories as well. It is important to note that negative genetic testing does not rule out disease due to a false-negative rate of 10%, despite testing panels that may include 25 separate genes. Bisphosphonate therapy may be beneficial, especially intravenous pamidronate and zoledronic acid in Type I and Type II OI. Teriparatide in adults with mild OI may be beneficial, and denosumab is being tested in OI patients as well. Teriparatide is not considered safe for children due to osteosarcoma risk. Corrective surgery, bracing, physical therapy, and continuous rehabilitative care are important.
