Description
Progressive pseudorheumatoid dysplasia (PPRD) is a joint disease that worsens over time. This condition is characterized by breakdown (degeneration) of the cartilage between bones (articular cartilage). This cartilage covers and protects the ends of bones, and its degeneration leads to pain and stiffness in the joints and other features of PPRD.
PPRD usually begins in childhood, between ages 3 and 8. The first indications are usually an abnormal walking pattern, weakness and fatigue when active, and stiffness in the joints in the fingers and in the knees. Other signs and symptoms that develop over time include permanently bent fingers (camptodactyly), enlarged finger and knee joints (often mistaken as swelling), and a reduced amount of space between the bones at the hip and knee joints. Hip pain is a common problem by adolescence. Affected individuals have flattened bones in the spine (platyspondyly) that are abnormally shaped (beaked), which leads to an abnormal front-to-back curvature of the spine (kyphosis) and a short torso. At birth, people with PPRD are of normal length, but by adulthood, they are usually shorter than their peers. Affected adults also have abnormal deposits of calcium around the elbow, knee, and hip joints and limited movement in all joints, including those of the spine.
PPRD is often mistaken for another joint disorder that affects young people called juvenile rheumatoid arthritis. However, the joint problems in juvenile rheumatoid arthritis are associated with inflammation, while those in PPRD are not.
Frequency
PPRD has been estimated to occur in approximately 1 per million people in the United Kingdom. The condition is thought to be more common in Turkey and the Middle East, although its prevalence in these regions is unknown. The condition in all regions is likely underdiagnosed because it is often misdiagnosed as juvenile rheumatoid arthritis.
Causes
PPRD is caused by mutations in the CCN6 gene. The function of the protein produced from this gene is not well understood, although it is thought to play a role in bone growth and cartilage maintenance. The CCN6 protein is made in cells called chondrocytes, which produce and maintain cartilage. This protein is associated with the production of certain proteins that make up cartilage, but its role in their production is unclear. CCN6 may also help control signaling pathways involved in the development of cartilage and bone and may help regulate the breakdown of cartilage components.
CCN6 gene mutations lead to an altered protein that may not function. Loss of CCN6 protein function likely disrupts normal cartilage maintenance and bone growth, leading to the cartilage degeneration and joint problems that occur in PPRD.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Progressive pseudorheumatoid arthropathy of childhood
- Spondyloepiphyseal dysplasia tarda with progressive arthropathy
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Garcia Segarra N, Mittaz L, Campos-Xavier AB, Bartels CF, Tuysuz B, Alanay Y, Cimaz R, Cormier-Daire V, Di Rocco M, Duba HC, Elcioglu NH, Forzano F, Hospach T, Kilic E, Kuemmerle-Deschner JB, Mortier G, Mrusek S, Nampoothiri S, Obersztyn E, Pauli RM, Selicorni A, Tenconi R, Unger S, Utine GE, Wright M, Zabel B, Warman ML, Superti-Furga A, Bonafe L. The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): a review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):217-29. doi: 10.1002/ajmg.c.31333. Epub 2012 Jul 12. Citation on PubMed
- Hurvitz JR, Suwairi WM, Van Hul W, El-Shanti H, Superti-Furga A, Roudier J, Holderbaum D, Pauli RM, Herd JK, Van Hul EV, Rezai-Delui H, Legius E, Le Merrer M, Al-Alami J, Bahabri SA, Warman ML. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Nat Genet. 1999 Sep;23(1):94-8. doi: 10.1038/12699. Citation on PubMed
- Spranger J, Albert C, Schilling F, Bartsocas C. Progressive pseudorheumatoid arthropathy of childhood (PPAC): a hereditary disorder simulating juvenile rheumatoid arthritis. Am J Med Genet. 1983 Feb;14(2):399-401. doi: 10.1002/ajmg.1320140224. No abstract available. Citation on PubMed
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