Invited editorial comment: Osteogenesis imperfecta: A pasture for splitters and lumpers

✍ Scribed by Spranger, J.

• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 206 KB
• Volume: 17
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320170205

✦ Synopsis

Ever since Looser [1906] discerned a congenita and a tarda group of osteogenesis imperfecta physicians have struggled to delineate more or less homogenous subsets of this disorder. None of the earlier classification systems has passed the test of time. Now the "Sillence classification'' tries to bring order into what had become a clinical geneticist's nightmare. How is he going to counsel his patients and their parents?

First proposed in 1979, the Sillence classification recognizes four main types of osteogenesis imperfecta, two relatively mild ones with autosomal dominant inheritance, and two severe, autosomal recessive ones. It now becomes clear that there is more heterogeneity. The dominant types are subdivided into A and B subtypes depending on the presence or absence of dentinogenesis imperfecta (Levin et al, 1978). In addition, there are a considerable number of cases which cannot be classified at present [Opitz, 1982; Spranger, 1982al. In their present paper, Professor Sillence and his associates present evidence for heterogeneity of their original type I1 osteogenesis imperfecta which they now divide into subgroups A, B, and C.

Subgroup IIA is the classical one with the "telescoped" long bones and beaded ribs. More heterogeneity must be anticipated in this subgroup. Though autosomal recessive inheritance is probable, the observation of two biochemically distinct proalpha 1 (I) chains in the collagen of a patient with that disorder is better explained by a dominant mutation [Barsh and Byers, 19811. Segregation analysis of this subgroup shows deficiency of affected sibs and a paucity of parental consanguinity (which is also compatible with the presence of some dominantly inherited cases).

Type IIC poses no major nosologic problems. It seems to be a rare disorder which is radiologically characterized by a peculiar nodular appearance of the ribs and long bones.