Abstract
Dominant mutations in the calcium permeable ion channel TRPV4 (transient receptor potential vanilloid 4) typically result in skeletal dysplasia or peripheral neuromuscular disease. However, the full spectrum of TRPV4-related phenotypes remains incompletely defined. This study systematically reviewed the clinical and genetic features of 10 Chinese patients harboring various TRPV4 variants. In the cohort, six patients were diagnosed with spondylometaphyseal dysplasia Kozlowski type (SMDK) and four patients with metatropic dysplasia (MD). The most common features involved spinal deformity (platyspondyly, kyphosis or scoliosis), and lower-limb malalignments (genu varum, genu valgum, or leg-length discrepancy). Two patients with MD had neurological deficits. The R594H and P799R substitutions were the most recurrent variants in our study. A novel variant (c.1628T>G, p.L543R) in the S2-S3 loop was identified. The study seeks to improve diagnostic precision by combining genetic and radiographic assessment, and highlights the importance of early spinal surveillance and multidisciplinary care to prevent neurological complications underlying TRPV4-mediated disorders.