title: COL2A1-related skeletal dysplasias with predominant metaphyseal involvement.
abstract: Skeletal dysplasias induced by mutations in the collagen 2 gene (the so-called "type 2 collagenopathies") form a wide spectrum in severity and are distinguished by subtle clinical and radiographic differential signs. The unifying features are predominant involvement of the vertebral bodies and the epiphyses of the long bones ("spondylo-epiphyseal" pattern). A mild degree of metaphyseal dysplasia can be seen in the so-called Strudwick variant of spondyloepimetaphyseal dysplasia and is generally mild or absent in other forms. We report here on four individuals with COL2A1 mutations associated with marked metaphyseal involvement with only mild epiphyseal and spondylar changes. One patient who carried a Gly283Arg substitution had a pattern of metaphyseal dysplasia that corresponded precisely to what was termed "Murdoch type metaphyseal dysplasia" in 1960s and was renamed Strudwick type SEMD in 1980s; the second patient carried a Gly181Arg substitution and had severe metaphyseal dysplasia with fractures at the metaphyses reminiscent of the "corner fractures" or Sutcliffe type spondylometaphyseal dysplasia. The third patient also had major metaphyseal involvement but more epiphyseal changes than the others in this study and had a Gly922Arg mutation in COL2A1. The final patient had a small in-frame deletion and unusually ballooned and distorted metaphyses. While it remains true that most individuals with COL2A1 mutations have chondrodysplasia with a spondylo-epiphyseal pattern, metaphyseal involvement is not incompatible with a COL2A1 dysplasia and mutation analysis can be indicated. The observation of these individuals with metaphyseal dysplasia indicates that the phenotypic spectrum associated with mutations in type 2 collagen, the main cartilage protein, is even wider than hitherto assumed.
authors.affiliation: Centre for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Walter
authors.forename: Mojca
authors.initials: M
authors.lastname: Tansek
authors.forename: Edward S
authors.initials: ES
authors.lastname: Tobias
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.forename: James
authors.initials: J
authors.lastname: Hyland
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iwaya
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
mesh_terms: D000293:Adolescent; D002648:Child; D024043:Collagen Type II / Q000235:genetics*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D006801:Humans; D006811:Humerus / Q000000981:diagnostic imaging; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000473:pathology*; D011859:Radiography; D013131:Spine / Q000000981:diagnostic imaging; D013977:Tibia / Q000000981:diagnostic imaging
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II