Osteogenesis imperfecta type III
Incidence
Autosomal dominant. Autosomal recessive. Caused by mutations in type I collagen alpha-1 polypeptide and type 1 collagen alpha-2 polypeptide.
Clinical Characteristics
Osteogenesis imperfecta type III is about one-eighth as frequent as dominantly inherited OI with blue sclerae. Scleral hue, which may be bluish at birth, usually normalizes with age. Patients reported in the literature with normal sclerae have shown progressive deformity of the limbs in childhood and of the spine in late childhood and adolescence. Dentinogenesis imperfecta is particularly striking, especially in the primary dentition. Children with type III osteogenesis imperfecta exhibit increased mortality like type II. OI type III shows prominent limb bowing, being intermediate in severity. Patients with type III 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. Short stature is the rule for osteogenesis imperfecta. Growth hormone therapy did increase growth velocity in several of these children, so endocrinology referral should be considered in children with severe short stature. Early and regular assessment of hearing and vision is also recommended because of sensorineural hearing loss, retinal detachment, and myopia that is frequent in osteogenesis imperfecta. Although congenital heart disease is not common, later aortic dilatation and mitral valve prolapse warrant careful cardiac examination during pediatric follow-up and formal cardiac assessment in adolescence or early adulthood.
Precipitants
none
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.