Aims-To determine the causes of death in patients with osteogenesis imperfecta, excluding infants with the perinatal lethal form (type II).

Unexplained fractures are characteristic of both osteogenesis imperfecta (OI) and non-accidental injury (NAI) but in most cases the diagnosis is straightforward. However, in a few OI patients an initial diagnosis of NAI is made. Factors contributing to such difficulties include failure to recognise that OI can occur without a family history, without blue sclerae, without osteopenia, without an excess of Wormian bones, or with metaphyseal fractures. In addition we report on 39 patients with an unusual history in that fractures only occurred in the first year of life. Rib fractures, metaphyseal abnormalities and periosteal reactions were common. The initial diagnosis was usually OI if the fractures occurred in hospital, but NAI if they appeared to have been sustained at home. Additional findings such as anaemia, vomiting, hepatomegaly, and apnoeic attacks were often found in these patients. The disorder has some similarities to the syndrome of infantile copper deficiency. Like the latter it is particularly common in preterm infants and in twins. Therefore, we are attempting to examine the incidence of significant hypocupraemia in unselected preterm infants. We suggest that the likely cause of this "temporary brittle bone disease" is a temporary deficiency of an enzyme, perhaps a metalloenzyme, involved in the post-translational processing of collagen.

Hearing impairment has long been recognized as a common feature in osteogenesis imperfecta. The figures in some publications could be taken to imply that, with increasing age, the proportion of osteogenesis imperfecta patients with hearing impairment approaches 100 per cent. The incidence of hearing loss in a large survey of 1394 patients with osteogenesis imperfecta was examined. It was found that the most common age of onset was in the second, third and fourth decades of life. At the age of 50 approximately 50 per cent of the patients had symptoms of hearing impairment; over the next 20 years there was little further increase. Differences were shown between patients with different clinical types of osteogenesis imperfecta as delineated in the Sillence classification; hearing loss was significantly less common in the type IV disease than in the type I disorder. Among the 29 families with osteogenesis imperfecta type IA there were distinct differences in the likelihood of hearing loss. These findings provide insights which will be valuable in giving patients advice on the likelihood of developing hearing loss in the future.

We report 12 patients with osteogenesis imperfecta initially diagnosed with nonaccidental injuries. As a result, formal hearings, care proceedings, and criminal proceedings ensued and seven of the children were removed from their parents. The features suggestive of osteogenesis imperfecta at the time of the initial investigation included a positive family history in six patients, scleral discoloration in nine, abnormally large anterior fontanels in four, excessive numbers of wormian bones in four, abnormal bone texture in two, and abnormal biochemical findings in three. There were discrepancies between the fractures and other clinical evidence of inflicted trauma. The seven patients removed from their homes eventually were returned. Five patients remained at home. Information was available on the subsequent history of the patients for an average of 4.8 years. Although seven patients have had additional fractures, there have been no additional allegations of nonaccidental injury. When investigating children with unexplained fractures, it is important to review carefully their clinical history, family history, physical examination findings, and radiographic findings. Misdiagnosing patients with nonaccidental injuries causes substantial harm to the family and particularly to the child.

Having seen a number of women with osteogenesis imperfecta who developed severe back pain during or just after pregnancy, we wished to determine the likelihood of this and other musculoskeletal problems in pregnancy. We interviewed by telephone 100 women with osteogenesis imperfecta who had, between them, 213 pregnancies between 1957 and 1998. For each pregnancy we recorded the Sillence type for the osteogenesis imperfecta, the mode of delivery and the musculo-skeletal complications. The most common problem was back pain, which was severe in or after 28 pregnancies (13.1%). There was no identifiable relationship to the type of osteogenesis imperfecta or to the mode of delivery. In many cases the back pain could be related to crush fractures of vertebrae. Other problems identified included spinal deformity, non-vertebral fractures, disc problems and ligament problems. We suggest that it may be appropriate to advise the avoidance of long periods of breast feeding in women with OI, particularly in those who have vertebral fractures.