Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome masquerading as juvenile idiopathic arthritis: a case series with a novel PRG4 variant and emphasis on bone health.

backgroundCamptodactyly-arthropathy-coxa vara-pericarditis syndrome is a rare autosomal recessive disorder caused by loss-of-function variants in the proteoglycan 4 gene, which encodes lubricin. It is frequently misdiagnosed as juvenile idiopathic arthritis, leading to prolonged immunosuppressive therapy. CASE PRESENTATION: We report two unrelated boys born to consanguineous parents who presented with progressive large-joint swelling and were initially diagnosed with juvenile idiopathic arthritis. Both received multiple disease-modifying and biologic agents without clinical response. Inflammatory markers remained persistently normal, and radiographs showed preserved joint spaces without erosive changes. Camptodactyly developed later in the disease course. One patient developed pericardial effusion and showed a reduced bone mineral density on dual-energy X-ray absorptiometry with limited hip motion and acetabular changes; the other patient showed only a qualitative radiographic image of a reduced bone mineral density but was not confirmed by dual-energy X-ray absorptiometry. Whole-exome sequencing identified a previously reported homozygous frameshift variant in proteoglycan 4 gene (c.2208del; p.Thr737ProfsTer175) in the first patient and a homozygous nonsense variant (c.4104T > A; p.Tyr1368Ter) in the second which was absent from ClinVar and Varsome (accessed April 2026) and it was classified as pathogenic by ACMG/AMP.

conclusionsCamptodactyly-arthropathy-coxa vara-pericarditis syndrome should be considered in children with non-inflammatory arthropathy unresponsive to immunosuppressive therapy. The recognition of the broader phenotypic burden including reduced bone mineral density supports the need for a standard method to assess bone health beyond the classical tetrad approach. Early whole-exome sequencing can shorten the diagnostic journey and redirect management toward appropriate supportive care.