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 skeletal 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.

Materials and methods: Thirteen patients with a mutation in TRPV4 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 spondylometaphyseal dysplasia Kozlowski type, three each with metatropic dysplasia and brachyolmia type 3, and one each with spondyloepiphyseal dysplasia Maroteaux type and congenital distal spinal muscular atrophy.

Results: Short stature and bone pain when running, walking, and climbing stairs occurred in patients with spondylometaphyseal dysplasia Kozlowski type and metatropic dysplasia from the age of 5 years and worsened with increasing age. Kyphosis was more pronounced with increasing age in these two groups of patients, while severe scoliosis occurred in brachyolmia type 3. In the radiographs of patients with spondylometaphyseal dysplasia Kozlowski type and metatropic dysplasia, severe platyspondyly persisted into adulthood or puberty. The patients with spondylometaphyseal dysplasia Kozlowski type exhibited irregular proximal femora leading to destruction of the femoral head towards the end of puberty, whereas metatropic dysplasia showed marked irregularity and widening of the femoral neck. We also observed that metaphyseal dysplasia in long bones other than the proximal femur was so inconspicuous that it could be ignored in patients with spondylometaphyseal dysplasia Kozlowski type.

Conclusion: Comparison of radiologic features that change with age in five different TRPV4-related skeletal dysplasias will be of great benefit in the management of this patient group.