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Pseudorheumatoid Dysplasia | Overview


Progressive pseudorheumatoid dysplasia is an autosomal recessive disorder that affects joints. Young children with PPD may appear less active and more prone to joint aches and pains than their peers. Often, the first sign of PPD occurring during mid-childhood is enlargement of the finger joints. This swelling may be mistaken for juvenile rheumatoid arthritis, but it can be distinguished from JRA by X-rays and laboratory studies. Patients with PPD have bony enlargement of the finger joints without evidence of inflammation. As children with PPD become older, they develop skeletal changes that resemble common osteoarthritis and their joints can become quite painful. Many teenagers and young adults with PPD have benefited from joint replacement surgery, which improves their pain and increases their mobility.

Most, if not all, patients with PPD have mutations in the gene WISP3. We first reported the identification of disease causing mutations in this gene in 1999.

Although we have found WISP3 mutations in a large number of patients with PPD, we were surprised to discover that mice lacking this gene do not develop PPD. We are still trying to understand why and how WISP3 protects joints and cartilage in humans, and is unnecessary in mice.

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

Pooling resources and sharing ideas is important for advancing our knowledge about PPD, 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. Are mutations in WISP3 the only cause of PPD?
  2. How does WISP3 function in human cartilage to protect against osteoarthritis?
  3. Why is WISP3 essential for human cartilage, but not for mouse cartilage?
  4. Can other organisms, such as zebrafish and fruitfly teach us about the biologic pathway in which WISP3 participates?

Interested in participating?

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

To better understand how WISP3 functions within the body, we are seeking joint material that is recovered from patients with PPD at the time of a diagnostic or medically-indicated procedure.

Studying the consequences of PPD 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 PPD are also welcome to contact us.