Skeletal phenotype/genotype in progressive pseudorheumatoid chondrodysplasia

Axial and extra-axial deceleration in function and progressive joint pain with subsequent development of antalgic gait associated with swellings, and stiffness of the joints with loss of the physiological spine biomechanics were the natural history in this group of patients. Clinical and radiological phenotypes have been analysed carefully to further understand the aetiology behind.

Seven patients (three children around the age of 9-11 and one child of 17 years old). Three adults aging 25, 30, 33 and 40 years old were seen and examined. The paediatric group of patients were initially diagnosed with myopathy followed later by juvenile rheumatoid arthritis in other institutions. Clinical and imaging documentation were collected in our departments, followed by mutation screening, was carried out by bidirectional sequencing of the WISP3 gene.

Clinical and radiological phenotypic studies confirmed the diagnosis of progressive pseudorheumatoid chondrodysplasia. A constellation of abnormalities such as early senile hyperostosis of the spine (Forestier disease), osteoarthritis of the hips showed progressive diminution and irregularities of the hip joint spaces associated with progressive capital femoral epiphyseal dysplasia and coxa vara have been encountered. Loss-of-function homozygous mutations (c.667T>G, p.Cys223Gly) and (c.170C>A, p.Ser57*) in the WISP3 gene were identified in our patients.

The definite diagnosis was not defined via vigorous myopathic and rheumatologic investigations. Detailed clinical examination and skeletal survey, followed by genotypic confirmation, were our fundamental pointers to rule out the false diagnosis of juvenile rheumatoid arthritis and rheumatoid polyarthritis in the adult group of patients. We wish to stress that the clinical/radiological phenotype is the baseline tool to establish a definite diagnosis and to guide the geneticist toward proper genotype.Key Points•Joint pain and difficulties in walking/climbing the stairs are characteristic features encountered in early childhood. False diagnosis of juvenile rheumatoid arthritis can be made at this point.•False positive-like muscular wasting resembling myopathy results in ensuing vigorous troublesome investigations.•Flattened vertebral bodies associated with defective ossification of the anterior end plates are characteristic features of progressive pseudorheumatoid chondrodysplasia.•Joint expansions, which are usually accompanied by narrowing of the articular ends of the appendicular skeletal system, show a clear radiological phenotype of pseudorheumatoid chondrodysplasia.