camptodactyly-arthropathy-coxa vara-pericarditis syndrome

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (also known as CACP syndrome) is a rare genetic rheumatologic condition that primarily affects the joints, skeletal structure, and, in some cases, the heart. It is caused by pathogenic variants in the PRG4 gene, which is responsible for producing lubricin, a protein essential for joint lubrication. The condition typically presents in early childhood with congenital or early-onset camptodactyly and progressive joint abnormalities. It is extremely rare, affecting fewer than 1 in 1,000,000 people.

Individuals with this syndrome often present with a range of musculoskeletal abnormalities. Characteristic findings include camptodactyly of both the fingers and toes, symmetrical polyarticular arthropathy affecting large joints such as the knees, elbows, and wrists, and progressive coxa vara deformity. Additional features noted in many affected individuals are wrist swelling, lumbar hyperlordosis, short femoral neck, and in some cases, complications like osteoporosis, bone cysts, osteoarthritis, and less commonly, non-inflammatory pericarditis or pleuritis. Not all individuals experience all features, and severity varies considerably.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome is caused by pathogenic variants in the PRG4 gene, which encodes lubricin—a protein that plays a crucial role in ensuring smooth joint movement and cartilage health. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected. It is more common when parents share a common ancestor because both may carry the same rare genetic variant. Genetic counseling is recommended to help families understand the recurrence risk and to explore options for family planning. Associated genes include PRG4.