Center for the Study of Genetic Skeletal Disorders | Camptodactyly Arthropathy Coxa Vara Pericarditis

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is an autosomal recessive disorder that mostly affects joints and tendons, but can also affect the pericardium and pleura, which are the surfaces that surround the heart and lungs, respectively.

The first sign of CACP, often noted at birth or within the first few months of life, is flexion contracture of one or more finger joints, which is termed camptodactyly. Older children with CACP develop painless swelling of their wrist, knee, and/or ankle joints. This painless swelling is termed arthropathy, and it does not appear to be associated with inflammation since affected joints are neither warm, red, or tender.

A biopsy of the tissue that encloses the joint space, called the synovium, is often necessary to diagnose of CACP.

Other findings that have been described in some persons with CACP are an angular deformity at the hip joint, termed coax vara, and an overgrowth of cells surrounding the heart, termed restrictive pericarditis.

Most, if not all, patients with CACP have mutations in the gene PRG4, which encodes the secreted protein now called lubricin. We first reported the identification of disease causing mutations in this gene in 1999. We initially called the protein CACP protein and other investigators, who were independently studying this protein called it by additional names, including Superficial Zone Protein, megakaryocyte stimulating factor, Proteoglycan 4, and hemangiopoeitin.

We have established an international consortium of patients, clinicians and basic scientists to study CACP. The goals of this consortium are to improve the diagnosis and treatment for persons affected with CACP.

Pooling resources and sharing ideas is important for advancing our knowledge about CACP, since we estimate that only 7000 persons in the entire world are affected with this rare disease.

Among the questions we want to answer are:

1. Is it possible to rapidly diagnose CACP using a blood test, rather than having to perform a biopsy of synovium?
2. What are the functions of lubricin within joints and tendons, and is it possible to replace these functions in persons with CACP?
3. Are unaffected relatives of patients with CACP at increased risk for developing common forms of joint disease, such as osteoarthritis?
4. Do acquired alterations in lubricin function increase one's risk for developing joint or tendon diseases?

Interested in participating?

We welcome individuals and families who are affected by CACP to participate in our research by contacting us.

To improve our ability to diagnose CACP without having to perform a synovial biopsy, we are seeking blood samples from patients with CACP and their unaffected relatives.

To better understand how lubricin functions within the body, we are seeking synovial tissue, synovial fluid, pericardial tissue, and tendon tissue that can be recovered from patients with CACP at the time of a diagnostic or medically-indicated procedure.

Studying the consequences of CACP at the cellular, biophysical, and protein levels may help in furthering the development of new therapeutic strategies.

Physicians seeking assistance in making a diagnosis of CACP are also welcome to contact us.