Camptodactyly-arthropathy-coxa vara-pericarditis syndrome masquerading as juvenile idiopathic arthritis: Clinical, familial, and genetic spectrum of a Libyan case series

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare autosomal recessive disorder associated with biallelic pathogenic variants in PRG4, encoding proteoglycan 4 (lubricin). Progressive joint enlargement, restricted mobility, and synovial involvement may closely mimic juvenile idiopathic arthritis (JIA), resulting in diagnostic delay and unnecessary immunosuppressive treatment. This study aimed to describe the clinical, familial, radiological, therapeutic, and genetic spectrum of CACP syndrome in Libyan children and highlight diagnostic clues that distinguish this non-inflammatory arthropathy from JIA. This study retrospectively reviewed four clinically characterized children representing three apparently unrelated Libyan pedigrees. Clinical manifestations, laboratory findings, imaging, treatment history, family history, pedigree data, and available whole-exome sequencing (WES) results were reviewed. All four children had congenital or early-onset camptodactyly, progressive non-inflammatory arthropathy, gait abnormality, and variable hip involvement. Autoimmune serology was negative, and inflammatory markers were generally normal or minimally elevated. Pericardial involvement occurred in selected affected individuals. Available WES in tested affected individuals demonstrated the same homozygous pathogenic PRG4 c.3254_3260del, p.(Ser1085^*) frameshift variant. Patients had previously received methotrexate, corticosteroids, and/or etanercept for presumed inflammatory arthritis. CACP should be considered in children with early camptodactyly, chronic non-inflammatory arthropathy, hip disease, waddling gait, negative autoimmune investigations, familial clustering, and poor response to JIA-directed therapy. Pedigree analysis and molecular confirmation are central to accurate diagnosis and genetic counseling.