title: Camptodactyly-arthropathy-coxavara-pericarditis syndrome in Saudi Arabia: clinical and molecular genetic findings in 22 patients.
abstract: BACKGROUND
  Camptodactyly-arthropathy-coxavara-pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by mutations in the gene proteoglycan 4 (PRG4), affecting lubricin production, which is an essential protein for joint function. Manifestations vary between affected individuals with camptodactyly, early-onsetnon-inflammatory arthropathy, coxa vara deformity and non-inflammatory pericarditis.
  
  
  OBJECTIVE
  To describe the clinical, laboratory, radiological and genetic findings of CACP syndrome in children from Saudi Arabia.
  
  
  METHODS
  Medical records of all the children with CACP syndrome seen between June 1990 and June 2012 at King Faisal Specialist Hospital and Research Center, Riyadh were reviewed. The data include gender,age of first disease manifestations,referral diagnosis, clinical and radiological features, and molecular genetic studies as well as functional status at the last follow-upvisit.
  
  
  RESULTS
  Twenty-two patients (15 boys), (clinical and genetic data of 15 patients were previously published) with mean age at diagnosis 3.7 (1-14) years, were included in this cohort study. The referral diagnosis was inaccurate in all patients; juvenile idiopathic arthritis (JIA) was the referral diagnosis in majority of the patients. Six families had more than one affected child. Camptodactyly and large joints arthropathy were present in all the cases. Camptodactyly was observed in the neonatal period in all the patients, while other joint involvement was observed through the 1st year of life. All patients had a normal cardiac evaluation but two children had evidence of pericarditis. All patients had normal inflammatory markers and the result for rheumatoid factor test was negative. Radiological findings included coxa vara with a short femoral neck and flat, irregular femoral heads and intra-osseous cysts, increased joint space, and abnormal modeling of the acetabulum with small iliac wings. Other joints (knees, ankle, elbow and wrist) showed soft-tissue swelling consistent with thick cartilage and abnormal modeling with evidence of intra-articular fluid in majority of the patients. Synovial biopsy from three patients revealed proliferating synovial epithelium with moderate fibro-collagenous densities and multinucleated giant cells, occasional lymphocytes or neutrophils were identified. Previously, a locus responsible for causing CACP syndrome has been reported in eight patients of our cohort; it has been assigned to 1q25-q31. Furthermore, in seven newly diagnosed patients from four unrelated families, five novel mutations were found. All patients were referred to us while they were on NSAIDs, 10 patients used antirheumatic drugs (prednisone and methotrexate) and two patients were treated with etanercept. In all patients, treatment was ineffective apart from mild pain relief.
  
  
  CONCLUSIONS
  CACP syndrome is an autosomal recessive disorder occurring due to mutations in the gene PRG4 encoding lubricin; it is not an uncommon disorder in Saudi Arabia. Pericarditis is rarely seen in our patients. Our data suggest that CACP syndrome may be easily confused with JIA, causing a delay in diagnosis and probably unnecessary treatment with antirheumatic drugs including biologic agents.
authors.affiliation: Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Intisar
authors.initials: I
authors.lastname: Albuhairan
authors.forename: Sulaiman M
authors.initials: SM
authors.lastname: Al-Mayouf
mesh_terms: D000293:Adolescent; D001177:Arthropathy, Neurogenic / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D060905:Coxa Vara / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D011509:Proteoglycans / Q000235:genetics*; D012529:Saudi Arabia; D013585:Synovitis / Q000175:diagnosis* / Q000235:genetics; D000099158:Proteoglycan 4
chemical_list: D011509:Proteoglycans; C419197:PRG4 protein, human; D000099158:Proteoglycan 4
keywords: Childhood arthropathy; Childhood rheumatic diseases; Contracture; Coxa vara; Familial arthropathy; Juvenile arthritis; Pediatrics; Saudi Arabia