Comparison of the natural course of clinical and radiologic features in 13 patients with TRPV4-related skeletal dysplasias

Background Heterozygous TRPV4 mutations cause a group of skeletal dysplasias characterized by short stature, short trunk, and spinal deformities. Objective The aim of this study is to compare the natural history of clinical and radiologic features of patients with different TRPV4 -related skeletal dysplasias. Material and methods Thirteen patients with a mutation in TRPV4 from 10 families were included in the study, and 11 were followed for a median of 6.5 years. The clinical phenotype of five patients was compatible with Kozlowski-type spondylometaphyseal dysplasia (SMDK), three each with classic form metatropic dysplasia (MD) and brachyolmia-3 (BCYM3), one each with the mild form of Maroteaux-type spondyloepiphyseal dysplasia (SEDM), and congenital distal spinal muscular atrophy (CDSMA). Results Short stature, and bone pain during running, walking, and stair climbing occurred in SMDK and MD patients after the age of 5 years and became more pronounced with increasing age. Kyphosis was more pronounced in SMDK and MD patients, and scoliosis in BCYM3 and CDSMA. Severe platyspondyly and delayed carpal ossification persisted into adulthood in SMDK and MD patients. Pelvic radiographs of SMDK patients showed irregular proximal femora leading to destruction of the femoral head towards the end of puberty while the marked widening of the femoral neck also occurred in MD. We noticed that metaphyseal dysplasia in long bones other than the proximal femur was so inconspicuous that it could be ignored in SMDK patients. Conclusion This study identified important radiologic features that vary by age in TRPV4 -related dysplasias and also intrafamilial variability in SMDK and BCYM3 families.