Osteogenesis Imperfecta type IV
Incidence
The estimated prevalence of the major types of osteogenesis imperfecta is about 1 in 20,000 individuals. Types I, III and IV were long known to exhibit autosomal dominant inheritance. Now it is realized that all major types of osteogenesis imperfecta involve mutations in the genes for type I collagen.
Clinical Characteristics
There are four major types of osteogenesis imperfecta, and more than a dozen additional syndromes include bone fragility as a component feature. Most common is type I osteogenesis imperfecta with short stature, fractures, blue sclerae, and normal life span. Perinatal lethal osteogenesis imperfecta is designated as type II, with types III (prominent limb bowing) and IV (normal sclerae) being intermediate in severity. The usual phenotype in osteogenesis imperfecta consists of short stature with a relatively large head (macrocephaly), small nose and chin with blue sclerae and abnormal teeth, joint laxity with dislocations, limb bowing, spinal curvature (kyphoscoliosis), hearing loss that increases with age, and easy bruisability. Less common complications include brain stem damage or hydrocephalus (accumulation of fluid in brain cavities) due to skull abnormalities, seizures, dilatation of large arteries (aortic aneurysm) or mitral valve prolapse, abdominal pain with constipation from protrusion of the hips into the abdomen, and kidney stones. Rarely, patients may have complications typical of weakened connective tissue such as retinal detachment or dilations of the aorta or cerebral arteries. Patients with type IV of osteogenesis imperfecta may be difficult to recognize in the neonatal period. Many present in early childhood for evaluation of short stature or recurrent fractures. It is the mildest form of the 4 types. They have normal sclerae. The presence of thin or deformed bones, fractures, blue sclerae and hearing loss is strongly suggestive of osteogenesis imperfecta, particularly when there is a family history.
Precipitants
Mild accidents may produce bone fractures.
Provocation Tests
None.
Diagnostic Procedures
Skeletal x-rays are often diagnostic, but biochemical and DNA testing for collagen abnormalities provide the most definitive diagnosis when they reveal an abnormality. Although DNA testing can be performed from blood samples, the variety of mutations in the osteogenesis imperfectas is too great to allow comprehensive screening. A better method for testing is to analyze collagen synthesis in cultured fibroblasts from skin biopsy. If an abnormality of collagen synthesis is detected in skin fibroblasts, then DNA testing for collagen gene abnormalities can be tried. Since mutations in type I collagen genes have been detected in all four types of osteogenesis imperfecta and in two types of Ehlers-Danlos syndrome, clinical correlation is still required for diagnosis and prognosis.