Treatment responses in five patients with ribbing disease including two with 466C>T missense mutations in TGFβ1

ObjectiveTo assess 5-year treatment responses and TGFB1 gene abnormalities in five patients with ribbing disease.MethodsPCR analysis and bidirectional sequencing of TGFβ1 exons 1 through 7 were performed in all five patients.ResultsThe 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.ConclusionConsiderable heterogeneity in the clinical presentations, genetic abnormalities, and treatment responses contribute to the diagnostic challenges raised by ribbing disease. Detailed genetic studies are needed.