A case report: camptodactyly-arthropathy-coxa vara-pericarditis syndrome: confirmation of a previously undescribed...

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is an inherited childhood noninflammatory arthropathy that can mimic juvenile idiopathic arthritis (JIA). It consists of congenital or early-onset camptodactyly with arthropathy, but not all patients develop hip or heart involvement. We present a compelling case report that underscores the pivotal role of synovial RNA sequencing in diagnosing and understanding hereditary arthropathies.

We report an 18-year-old man with presumed recalcitrant JIA who had a previously undescribed mutation, p.Glu940*, resulting in a recognised phenotype of CACP syndrome. Diagnosis was confirmed with the aid of synovial tissue single-cell RNA sequencing.

Whole genome sequencing identified heterozygous PRG4 variants, including a nonsense mutation (p.GLU940*) and a splice-site variant initially classified as of uncertain significance. Synovial RNA analysis demonstrated aberrant splicing leading to an out-of-frame transcript, allowing reclassification of the splice-site variant as likely pathogenic.

Our report signifies the inaugural utilisation of synovial RNA sequencing to confirm the pathogenicity of a PRG4 variant, marking a significant stride in the diagnostic landscape of genetic arthropathies. Importantly, it sheds light on the crucial consideration of JIA mimics during atypical clinical presentations. The realisation that the disease course and clinical features do not align with the anticipated pattern underscores the necessity of broadening the diagnostic scope beyond conventional frameworks.