Background/Purpose:

The aim of this study was to report families of Blau’s syndrome with unusual NOD2 gene variants.

Methods:

Two proband patients were seen, and their clinical phenotypes and genotypes were analyzed. Pedigree charts of both families were made.

Results:

Proband A, a white 57-year-old woman, noticed painless flexion contractures of her 3^rd, 4^th and 5^th proximal interphalangeal joints (PIPs) of both hands at age 6. She developed inflammatory polyarthritis and intermittent facial erythematous plaques/patches since age 30. As a result of cough and dyspnea, chest radiograph and computerized tomography showed multiple lung nodules without hilar adenopathy noted, and subsequent mediastinal lymph node biopsy revealed noncaseating granuloma. These symptoms markedly improved with prednisone 40 mg daily with taper. She had dry eyes on cyclosporine drops without uveitis. There were right parotid gland enlargement consistent with peiomorphic adenoma and left scanty granuloma composed of lymphocytes and mixed with debris and rare collections of histocytes. There was low grade fever. Her erythrocyte sedimentation rate (ESR), antinuclear antibodies, and blood CD4, CD8, and NK cell counts were all normal.  Her blood vascular endothelial growth factor and TNFa levels were normal. A positive family history included flexion contractures of the 4^th and 5^thPIPs (Photographs and Pedigree chart). On examination, there was camptodactyly of the PIPs 3, 4 and 5 of both hands. Genetic testing revealed the presence of the NOD2 variant IVS8+158 in the patient, daughter and son.

Proband B, a white 50-year-old woman, developed inflammatory polyarthritis during the previous 5 months. She also had aching skin and subcutaneous nodules over her elbows, wrists and knees.  She complained of mild dry eyes and mouth without parotid gland enlargement or fever; ophthalmic examination showed no evidence of uveitis. A positive family history involved flexion contractures of the 5^thPIPs in several members (Pedigree chart). On examination, there were minimally tender and mobile subcutaneous nodules of 0.5 to 1.5 cm over the joints (Photograph). Her ESR and serologic testing were normal. A skin nodule biopsy showed non-necrotizing granuloma. Genetic testing revealed the presence of the NOD2 mutation R703C. These nodules resolved after 2 months of treatment with sulfasalazine.

Conclusion:

Both families have autosomal dominant phenotypes of Blau’s syndrome.  Proband A has familial NOD2 IVS8+158, and proband B is linked to the NOD2 R703C. This study indicates that Blau’s syndrome is also associated with the NOD2 variants away from the commonly reported nucleotide binding region and may present as an adult-onset disease.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/two-family-kindreds-with-blaus-syndrome-associated-with-unusual-nod2-mutations/