Besides brittle bones, all other clinical characteristics of osteogenesis imperfecta (OI) are variable, and even different members of the same family may present with a dissimilar degree of severity [
1]. Severity appears to follow a continuum in the OI population, and it is therefore very difficult to establish a clinical prognostic classification in definite categories. This disease has received different names through history, including osteopsathyrosis, Vrolik's disease, fragilitas ossium, mollities ossium, Lobstein's disease, and Van der Hoeve syndrome [
2]. In a first attempt to classify OI, in 1906 Looser divided the disease in two forms [
3]: "congenita" (Vrolik) and "tarda" (Lobstein), depending on the severity of the presentation. In OI congenita, multiple fractures may occur
in-utero, whereas in OI tarda, fractures happen at the time of birth or later. OI tarda has also been sub-divided in "gravis" and "levis" [
3]. This classification is no longer tenable because it failed to encompass the obvious clinical variability apparent in this disorder. There has also been an attempt to classify OI according to radiological characteristics [
4]. Some of the features suggested by the authors of this classification are not present until age 5 or 10 years, and children of early ages can not be classified using this scheme. There has also been suggested that OI could be classified OI according to severity [
5,
6]. The most commonly used classification, initially proposed by Sillence in 1979, divides the patients in four types (I-IV) [
7,
8]. In fact, it is now widely recognized that there may be more types of OI [
9‐
11]. Some of the forms of congenital brittle bones have been considered OI and have been added as numbers V, VI and VII [
8,
12‐
14], while others have been designated with eponyms (Cole-Carpenter syndrome [
15], Bruck syndrome [
16]), and others designated with clinical features (OI with denser areas in bones [
17], OI with optic atrophy, retinopathy, and severe psychomotor retardation [
18], OI with microcephaly, and cataracts [
19], osteoporosis-pseudoglioma syndrome). The numeric classification (I-VII) is somewhat confusing, as the characteristics of each type overlap. Furthermore, there is no consensus about basic characteristics of the different types. For example, it is not clear if type I OI includes individuals with short stature, or if bone deformity rules out the diagnosis of Type I OI. Also, it is unclear if an individual with normal height can have type IV OI. Type II OI is defined as lethal, but there are cases of children with clinical characteristics of type II OI who have survived several years. Furthermore, the current classification does not allow for prognostic predictions, as individuals with type I OI may have numerous fractures and chronic pain in the course of their lives. This is part of the lack of a precise definition of OI. Thus, despite the fact that OI has been known for more than 200 years, there is no consensus about the definition for the disease. For some, it includes only those forms of congenital brittle bones secondary to mutations in the genes codifying for type I pro-collagen (COL1A1 and COL1A2). For others, it is a group of conditions with the common feature of congenital brittle bones. The example of the osteogenesis imperfecta-pseudoglioma syndrome illustrates this concept very clearly. This syndrome has been re-named as "osteoporosis-pseudoglioma syndrome" once the causal mutation has been identified to be in the LRP5 gene, elsewhere than the type I pro-collagen genes [
20,
21]. Following this example, I propose to define osteogenesis imperfecta as syndromes resulting from mutations in either COL1A1 or COL1A2 genes, and to group all other syndromes with congenital brittle bones as "syndromes resembling OI" (SROI), pending the identification of their causal mutation. Here, a review of the different forms of syndromes with congenital brittle bones is presented (Table
1). A working-group of international experts (like the Villefrance criteria in Ehlers-Danlos Syndrome) to clarify the issue of definition of congenital brittle bones syndromes and their classification is warranted.
Table 1
syndromes with congenital brittle bones
Osteogenesis Imperfecta |
Mild OI with normal stature |
Moderate OI with short stature |
Severe OI |
Lethal OI |
Congenital brittle bones with dense areas in bones |
Syndromes resembling OI (SROI) |
Congenital brittle bones with craniosynostosis and ocular proptosis |
Congenital brittle bones with congenital joint contractures |
Osteoporosis-pseudoglioma syndrome |
Congenital brittle bones with optic atrophy, retinopathy and severe psychomotor retardation |
Congenital brittle bones with microcephaly and cataracts |
Congenital brittle bones with redundant callus |
Congenital brittle bones with mineralization defect |
Congenital brittle bones with rhizomelia |