title: Two novel COL2A1 mutations associated with a Legg-Calvé-Perthes disease-like presentation.
abstract: BACKGROUND
  Abnormal development and growth of the capital femoral epiphysis and acetabulum are associated with a wide variety of underlying etiologies, one of which is Legg-Calvé-Perthes disease.
  
  
  METHODS
  We report the cases of two children who presented with abnormal development of both hips and in whom novel mutations in the COL2A1 gene were found. These cases illustrate the importance of identifying individuals with a type II collagen abnormality, as it informs management, allows investigation for other complications, and provides the opportunity for accurate genetic counseling and consideration of other family members who might be at risk.
  
  
  METHODS
  The literature documents numerous private mutations in COL2A1 associated with diverse clinical phenotypes including bilateral hip dysplasia and premature osteoarthritis. Some of these mutations are associated with a joint-specific phenotype but few other skeletal or extraskeletal manifestations. Only careful clinical examination of children presenting with hip anomalies therefore will reveal additional findings that warrant an evaluation by a clinical geneticist. DNA mutation analysis may be useful for making a specific diagnosis and identifying other at-risk family members.
  
  
  CONCLUSIONS
  The purpose of our report is to alert clinicians to the possibility that children who present with bilateral Perthes-like disease of the hip might have an underlying mutation in the gene encoding type II collagen. It is important to consider this in the differential diagnosis and workup of such children as it has specific prognostic, clinical, genetic counseling, and reproductive sequelae.
authors: Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada. peter.kannu@sickkids.ca
authors: Peter
authors: P
authors: Kannu
authors: Melita
authors: M
authors: Irving
authors: Salim
authors: S
authors: Aftimos
authors: Ravi
authors: R
authors: Savarirayan
mesh_terms: D002675:Child, Preschool; D024043:Collagen Type II / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004838:Epiphyses / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007873:Legg-Calve-Perthes Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D004247:DNA