title: Treatment responses in five patients with Ribbing disease including two with 466C>T missense mutations in TGFβ1.
abstract: OBJECTIVE
  To assess 5-year treatment responses and TGFB1 gene abnormalities in five patients with ribbing disease.
  
  
  METHODS
  PCR analysis and bidirectional sequencing of TGFβ1 exons 1 through 7 were performed in all five patients.
  
  
  RESULTS
  The five patients, four women and one man with a mean age of 34 years at symptom onset, shared the following features: severe diaphyseal pain predominating in the lower limbs with diaphyseal hyperostosis; increased radionuclide uptake at sites of pain and, in some cases at other cortical sites; asymmetric or asynchronous lesions; long symptom duration (5-18 years) despite a variety of treatments; and a delay of several years (2-15) between symptom onset and the diagnosis. Of our five patients, two had a heterozygous missense mutation in exon 2 of TGFβ1 (c.466C>T, p.Arg156Cys, previously described in Camurati-Engelmann syndrome) and three had commonly found TGFβ1 polymorphisms. Intravenous bisphosphonate therapy was used in all five patients but induced substantial improvements in a single patient. Of the three patients given bolus methylprednisolone therapy, two experienced a lasting response; the exception was one of the two women with a TGFβ1 mutation.
  
  
  CONCLUSIONS
  Considerable heterogeneity in the clinical presentations, genetic abnormalities, and treatment responses contribute to the diagnostic challenges raised by ribbing disease. Detailed genetic studies are needed.
authors: Service de Rhumatologie, Hôtel-Dieu, CHU de Nantes, 44093 Nantes cedex 01, France.
authors: Anne
authors: A
authors: Savoie
authors: François
authors: F
authors: Gouin
authors: Yves
authors: Y
authors: Maugars
authors: Bertrand
authors: B
authors: Isidor
authors: Catherine
authors: C
authors: Larrose
authors: Jean-Marie
authors: JM
authors: Berthelot
mesh_terms: D000328:Adult; D000368:Aged; D003966:Camurati-Engelmann Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D004164:Diphosphonates / Q000008:administration & dosage; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010017:Osteoma, Osteoid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D004164:Diphosphonates; D005938:Glucocorticoids; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Bisphosphonate; Camurati-Engelmann syndrome; Glucocorticoids; Hyperostosis; Multiple diaphyseal sclerosis; Ribbing disease; TGF-beta-1; Treatment