Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory arthropathy, shown to be caused by mutations in the WNT1-inducible signaling pathway protein 3 (WISP3) gene. Although several hundred cases were reported, the diagnosis remains challenging and elusive. Subsequently, the syndrome is often unrecognized and misdiagnosed, leading to unnecessary procedures and treatments.
We present here a multiply affected consanguineous family of Iraqi Jewish descent with PPRD. The proband, a 6.5 years old girl, had presented with bilateral symmetric bony enlargements of the 1st interphalangeal joints of the hands, without signs of synovitis. Extensive evaluation ensued however did not bring to a diagnosis. Molecular analysis by Whole Exome Sequencing and homozygosity mapping identified a novel homozygous missense mutation (c.G257T, p.C86F) in the WISP3 gene. Following this diagnosis, an additional 53 years old affected family member was found to harbor the mutation. Two other individuals in the family were reported to have had similar involvement however both had died of nonrelated causes.
The reported family underscores the importance of recognition of this unique skeletal dysplasia by clinicians, and especially pediatric rheumatologists and orthopedic surgeons.
