NeurometPlus

Incidence

Autosomal dominant. Caused by mutations in the collagen I, alpha-1 gene (COL1A1). Update 2017 by MGJM.

Clinical Characteristics

Osteogenesis imperfecta (OI) is a group of rare disorders affecting the connective tissue and characterized by extremely fragile bones that break or fracture easily (brittle bones), often without apparent cause. The specific symptoms and physical findings associated with OI vary greatly from case to case. The severity of OI also varies greatly, even among individuals of the same family. OI may be a mild disorder or may result in severe complications. Four main types of OI have been identified. OI type I is the most common and the mildest form of the disorder. OI type II is the most severe. In most cases, the various forms of osteogenesis imperfecta are inherited as autosomal dominant traits. Most common is type I osteogenesis imperfecta with short stature, fractures, blue sclerae, and normal life span. Normal to near normal stature. Height often shorter than unaffected family members. Normal teeth. The presence of thin or deformed bones, fractures, blue sclerae (whites of the eyes), and hearing loss is strongly suggestive of osteogenesis imperfecta, particularly when there is a family history. Skeletal x-rays are often diagnostic, but biochemical and DNA testing for collagen abnormalities provide the most definitive diagnosis when they reveal an abnormality. OI type 1 osteogenesis imperfecta is characterized by short stature, fractures, deafness, and blue sclerae. 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.

Precipitants

none

Provocation Tests

none

Diagnostic Procedures

The presence of thin or deformed bones, fractures, blue sclerae (whites of the eyes), and hearing loss is strongly suggestive of osteogenesis imperfecta, particularly when there is a family history. 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.