Familial Arthropathy Research Articles

Syndrome of progressive deforming non-inflammatory arthritis of childhood: two patients of camptodactyly-arthropathy-coxa vara-pericarditis syndrome

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare familial arthropathy of childhood, commonly misdiagnosed as juvenile idiopathic arthritis. It is characterized by non-inflammatory arthropathy, coxa vara deformity, and sterile pericarditis. We describe two children with CACP syndrome who were referred to the rheumatology clinic for the suspicion of inflammatory arthritis. A literature search was carried out using PubMed/ Medline and Embase databases. English language reports of mutation-proven cases of CACP syndrome reported until 31 March 2020 were retrieved and analysed. Both the children had a delay in diagnosis (age at diagnosis- 12 and 13years, respectively) and had received immunomodulatory therapy for suspected inflammatory arthritis. Presence of symmetrical arthropathy of large joints, camptodactyly, and normal inflammatory parameters are clues that indicated CACP syndrome. One child with a novel variant in PRG4 also had associated mitral valve prolapse and regurgitation. Both had severe constrictive pericarditis requiring pericardiectomy. On literature review, a total of 98 mutation-proven cases of CACP syndrome have been reported till date. Arthropathy in CACP syndrome mainly involves knees, wrists, ankles, and hips. Pericarditis is usually mild, however, can present rarely with severe symptoms requiring surgical intervention. CACP syndrome can closely mimic inflammatory arthritis and early clinical recognition is important to avoid misdiagnosis. Molecular confirmation is essential for early diagnosis and future genetic counselling for affected families.

Axial involvement with facet joint arthropathy and bony ankylosis in a case of camptodactyly, arthropathy, coxa vara, pericarditis (CACP) syndrome

Familial arthropathy associated with congenital camptodactyly has been previously recognized as a definite clinical entity in the literature. The clinical spectrum of this disease seems to be variable. The typical features of congenital camptodactyly, arthropathy, coxa vara and pericarditis (CACP syndrome) appear to be a more frequent presentation in children from the Middle East and North Africa. Musculoskeletal presentation of this rare familial form of arthropathy is unique and heterogeneous. In all previous reports, non-inflammatory pattern of arthropathy involving the peripheral joints with typical coxa vara deformity were described, and in a few cases spine abnormalities, including kyphosis, lordosis, or scoliosis. We describe the first case of axial involvement in a typical case of CACP syndrome with facet joint arthropathy and ankylosis at L5/S1 levels.

Familial Arthropathy in Saudi Arabian Children: Demographic, Clinical, and Biochemical Features

Familial arthropathy comprises a heterogeneous group of arthropathies. It can be either an inflammatory or a noninflammatory condition. The worldwide frequency of these disorders is unknown. To study the demographic, clinical and biochemical features, and survival of a large series of children with familial arthropathies. The medical records of children who had an arthropathy and a family history of a similar condition at the Pediatric Rheumatology Clinic at King Faisal Specialist Hospital-Riyadh between 1990 and 2005 were reviewed. These included children with familial juvenile idiopathic arthritis (FJIA), infantile systemic hyalinosis (ISH), the nodulosis-arthropathy-osteolysis (NAO) syndrome, and the camptodactyly-arthropathy-coxa vara (CAC) syndrome. Familial rheumatic diseases including spondyloarthropathies or known syndromes associated with articular manifestations were excluded. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, and provisional and final diagnoses as well as treatment and outcome were reviewed. Sixty-two children with various familial arthropathies were reviewed. Twelve children (9 female/3 male) with FJIA presented with polyarthritis. These children belonged to 4 unrelated families, all of whom were from the same geographical area, with 2 families belonging to the same tribe. The mean age at onset was 2.4 years, and mean age at diagnosis was 3.5 years. All children had high inflammatory markers. Nineteen children (11 male/8 female) with ISH presented in the neonatal period with painful joint contractures and typical mucocutaneous features. The referral diagnosis was inaccurate in 14 patients. Thirteen patients were the product of first-degree cousin marriages, and 5 families had more than 1 affected child. Radiological findings included periosteal reaction and osteolytic lesions. Tissue biopsy was performed in 8 patients and the findings were consistent with the diagnosis in all 8 patients. Despite aggressive management, 16 patients died. The mean age of the remaining 3 surviving children was 20 months. There were 15 children (9 female/6 male) with the NAO syndrome with a mean age at onset of 3.4 years. They were from 7 unrelated families; 5 families had more than 1 affected child. The referral diagnosis was juvenile idiopathic arthritis (JIA). Most children presented with painful deformed hands. Eleven children (70%) had advanced osteolytic changes. All children had normal inflammatory markers. There were 16 children (11 male/5 female) with the CAC syndrome who were diagnosed at a mean age of 3.7 years. Camptodactyly presented at birth or in first months of life, while other features developed in early childhood. JIA was the referral diagnosis. Fourteen children had bilateral coxa vara. Two children exhibited symptoms or signs of pericarditis. Inflammatory markers were normal in all children. Familial arthropathies are not uncommon conditions which may be easily confused with JIA, causing a delay in diagnosis and management. Careful evaluation of a child presenting with an arthropathy, particularly in a population where consanguinity is common, is required for timely and accurate diagnosis. Overall, the prognosis of these conditions remains guarded despite treatment.

Radiological findings in NAO syndrome.

Diseases exhibiting osteolysis in children are rare hereditary conditions. Several types have been recognised with different clinical manifestations. One type includes subcutaneous nodules, arthropathy and osteolysis and has been termed NAO syndrome. Previous radiological reports have described the affected bones, usually the carpal and tarsal regions, but a detailed analysis of the radiological findings of both the axial as well as the appendicular skeleton has not been reported. To describe the radiological findings in a large group of children with an autosomal recessive disease characterized by nodules, familial arthropathy and osteolysis. The study comprises 14 patients from 9 families and all patients had the triad of nodulosis, arthropathy and osteolysis (NAO). The most common radiological manifestations were osteopenia, undertubulation of long bones, arthritic changes, sclerotic sutures of the calvaria, osteolysis and muscle contractures. Other common findings were squared vertebrae, broad medial clavicles and brachycephaly. Progress of disease was documented in more than half of the patients. Our study is the first report of the detailed radiological findings of NAO syndrome. In NAO syndrome, both the axial and appendicular skeleton are involved

Syndrome of Camptodactyly, Arthropathy and Coxa Vara (Cac Syndrome)

Three Saudi children (two female, one male) are described who presented with familial arthropathy associated with congenital camptodactyly. This rare but recognized clinical entity has a variable clinical presentation and may be associated with pericarditis and coxa vara. Camptodactyly was observed in the neonatal period in all patients, while joint swelling was observed between the third and 11th month. Pericarditis was suspected in the referral hospital in one patient but was not subsequently confirmed at our institution, raising the possibility that pericarditis may be reversible. Radiological examination of the hips showed coxa vara with short femoral neck in all patients. Synovial biopsy in the three patients revealed proliferating synovial epithelium with moderate fibrocollagenous densities and multinucleated giant cells, occasional lymphocytes or neutrophils but no plasma cells were identified. This is the first series of this familial arthropathy with a triad of camptodactyly, arthropathy and coxa vara (CAC syndrome) in Saudi Arabia which is to be considered in patients where more than one family member has juvenile arthritis.

Radiological features in congenital camptodactyly, familial arthropathy and coxa vara syndrome.

The association of congenital camptodactyly, familial arthropathy and coxa vara is a rare but recognized clinical entity. The radiological manifestations were reviewed in five patients. In the hips, coxa vara, short broad femoral necks and intraosseous cysts were demonstrated in all patients. Abnormal modeling of the acetabulum, increased joint space, effusion, small iliac wings and intraosseous herniation of fluid were found in four out of five patients. Somewhat flat, slightly irregular femoral heads were seen in three patients. In the knees, effusion was demonstrated in all five patients and thick cartilage in three. The elbow, wrist and ankle joints showed abnormal modeling with evidence or suspicion of intraarticular fluid in the majority of patients. Flexion deformities of the fingers were seen in all patients.

Autosomal dominant arthropathy in a french family

We studied a French family in which 18 adult members had destructive arthropathy and enthesopathic changes. In 16 patients, the diagnosis was verified radiologically, and in the 2 other patients, the clinical history was consistent with familial arthropathy. The disease predominantly affects the wrists, fingers, shoulders, and peripheral entheses, and its onset occurs after age 18. Genetic transmission is autosomal dominant, with 100% penetrance, and is not related to the HLA system. The clinical and radiologic features are strikingly similar in all patients in successive generations and different branches of the genealogic tree, and this suggests monogenic transmission.

Hereditary chondrocalcinosis in a Mexican-American family.

In a study of 45 adults in a family of Mexican-Indian ancestry, it was found that 22 (49%) had joint symptoms resembling those of degenerative joint disease. Eleven family members had radiographic evidence of chondrocalcinosis, and 1 adult and 3 adolescents had clinical histories and examinations consistent with the familial arthropathy, but no radiographic evidence of disease. The cause of the arthritis in the affected family members is calcium pyrophosphate crystal deposition. The mode of inheritance appears to be autosomal dominant with a high degree of penetrance. The disease is characterized by onset in the second to fifth decades of either episodes of acute inflammatory arthritis or degenerative joint disease. A unique finding of this study was a "halo" surrounding chondrocytes in 1 patient's cartilage, demonstrating loss of the proteoglycans.