Camptodactyly-arthropathy-coxa vara-pericarditis syndrome is a rare

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic medical condition due to a mutation in the gene proteoglycan 4 (

PRG4 Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the ''PRG4'' gene. It acts as a joint/boundary lubricant. Function Lubricin is present in synovial fluid and on the surface (superficial layer) of articular cartilage ...

) – a mucin-type glycoprotein that acts as a lubricant for the cartilage surfaces. This gene is also known as lubricin.

Presentation

This condition was first described in 1986.Bulutlar G, Yazici H, Ozdogan H, Schreuder I (1986) A familial syndrome of pericarditis, arthritis, camptodactyly and coxa vara. Arthritis Rheum 29:436–438 and is a syndrome of camptodactyly, arthropathy, coxa vara, and

pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...

.Offiah AC, Woo P, Prieur AM, Hasson N, Hall CM (2005) Camptodactyly-arthropathy-coxa vara-pericarditis syndrome versus juvenile idiopathic arthropathy. AJR Am J Roentgenol 185(2):522-529 It may also include congenital cataracts.Akawi NA, Ali BR, Al-Gazali L (2012) A novel mutation in PRG4 gene underlying camptodactyly-arthropathy-coxa vara-pericarditis syndrome with the possible expansion of the phenotype to include congenital cataract. Birth Defects Res A Clin Mol Teratol doi: 10.1002/bdra.23031. The cause of this syndrome was discovered in 1999.Marcelino J, Carpten JD, Suwairi WM, Gutierrez OM, Schwartz S, Robbins C, Sood R, Makalowska I, Baxevanis A, Johnstone B, Laxer RM, Zemel L, Kim CA, Herd JK, Ihle J, Williams C, Johnson M, Raman V, Alonso LG, Brunoni D, Gerstein A, Papadopoulos N, Bahabri SA, Trent JM, Warman ML (1999) CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Nat Genet 23(3):319-322 Children with this syndrome often present with a joint effusion that is cool and resistant to anti-inflammatory therapy. The arthropathy principally involves large joints such as elbows, hips, knees, and ankles. Pericarditis may be a presenting feature or may occur later in the course of the disease. Coxa vara occurs in 50–90% of cases and noninflammatory pericarditis in 30%.

Genetics

The gene responsible for this condition is located on the long arm of chromosome 1 (1q). The encoded protein is a

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

of ~345 kDa specifically synthesized by

chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...

s located at the surface of articular cartilage, and also by some synovial lining cells. The cDNA encodes a protein of 1,404 amino acids (human A isoform) with a

somatomedin B Somatomedin B is a serum factor of unknown function, is a small cysteine-rich peptide, derived proteolytically from the N-terminus of the cell-substrate adhesion protein vitronectin. Cys-rich somatomedin B-like domains are found in a number o ...

homology domain,

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...

-binding domains, multiple mucin-like repeats, a hemopexin domain, and an aggregation domain. There are 3 consensus sequences for N-glycosylation and 1 chondroitin sulfate substitution site.

Diagnosis

Laboratory

The full blood count, erythrocyte sedimentation rate and C reactive protein are normal. Synovial fluid is typically viscous, clear, honey-colored, and low in cell count. Synovial histology shows little or no mononuclear infiltration. Mild thickening of the

synovium The synovial membrane (also known as the synovial stratum, synovium or stratum synoviale) is a specialized connective tissue that lines the inner surface of capsules of synovial joints and tendon sheath. It makes direct contact with the fibrous ...

is present and giant cells may be occasionally seen.

Radiology

Large acetabular cysts are common in this condition. Other features include periarticular osteopenia, squaring of metacarpals and

phalanges The phalanges (singular: ''phalanx'' ) are digital bones in the hands and feet of most vertebrates. In primates, the thumbs and big toes have two phalanges while the other digits have three phalanges. The phalanges are classed as long bones. ...

and bilateral joint effusions.

Management

References

External links

{{Medical resources , ICD10 = , ICD9 = , ICDO = , OMIM = 208250 , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 2848 Genetic diseases and disorders Syndromes