What is this condition?
She has osteogenesis imperfecta, but not the perinatal lethal form (type II). She most likely has type I. Type III is seen in children and adults, but is more severe. Type IV is hard to distinguish from type III.
OI causes osteopenia ("brittle bones") and predisposes to fractures. Patients often have blue sclerae, dental abnormalities, and progressive hearing loss. The perinatal form leads to death in utero, at birth, or shortly thereafter.
The course of mild and moderate forms is more variable. Some patients appear normal at birth and become progressively worse. Some have multiple fractures in infancy and childhood, improve after puberty, and fracture more frequently later in life.
What is the inheritance pattern?
Type I OI is usually autosomal dominant with a frequency of about 1 in 30,000.
Type II OI typically results from spontaneous new autosomal dominant mutations. The frequency of another fetus with lethal OI in the same family is about 7% because of germ-line mosaicism in one of the parents. Type II OI has a reported incidence at birth of about 1 in 60,000.
What is the biochemical defect?
The typical mutations of OI involve one of the two genes that encode type I procollagen. Over 90% of patients with type I OI and blue sclerae have mutations in the pro1(I) gene that decrease the steady-state levels of the mRNA for pro1(I) chains and decrease the rates of synthesis of pro1(I) chains relative to those for pro2(I) chains.
In more severe forms (types II, III, and IV), the effects of mutations that cause synthesis of abnormal pro chains are amplified.
Explain the appearance of her eyes.
The sclerae can be normal, slightly bluish, or bright blue. The color is probably caused by a thinness of the collagen layers of the sclerae that allows the choroid layers to be seen. Blue sclerae, however, are an inherited trait in some families who do not have increased bone fragility.
What is the reason for the hearing loss?
With OI, the bone of the middle ear does not develop properly. There can be maldevelopment, deficient ossification, persistence of cartilage, and abnormal calcium deposition.
Hearing loss usually begins during the second decade of life and occurs in over 50% of subjects over age 30. The loss can be conductive, sensorineural, or mixed and varies in severity.
What is the reason for the dental imperfections?
She has dentinogenesis imperfecta. The tooth enamel appears normal, but the teeth may have a characteristic amber, yellowish brown, or translucent bluish gray color because of improper deposition or deficiency of dentin. The defect in dentin is directly attributable to the fact that normal dentin is rich in type I collagen. Similar tooth defects, however, can be inherited without any evidence of OI.
What happens to patients with this disorder?
Most patients with type I can function well despite deformities. Those with mild disorder may need little treatment when fractures decrease after puberty, but women require special attention during pregnancy and after menopause, when fractures again increase.
More severely affected children require a comprehensive program of physical therapy, surgical management of fractures and skeletal deformities, and vocational education. Treatment with bisphosphonates to decrease bone loss has been introduced on an experimental basis.
