In childhood, 2 distinct types of sarcoidosis have been described (Shetty and Gedalia, 1998). Usually the disease is detected in older children by chest radiography, and the clinical manifestations are characterized by a classic triad of lung, lymph ... In childhood, 2 distinct types of sarcoidosis have been described (Shetty and Gedalia, 1998). Usually the disease is detected in older children by chest radiography, and the clinical manifestations are characterized by a classic triad of lung, lymph node, and eye involvement, similar to those in adults with sarcoidosis (181000). In contrast, early-onset sarcoidosis (EOS), which usually appears in those younger than 4 years of age, is rare and has a distinct triad of skin, joint, and eye disorders, without apparent pulmonary involvement. Compared with an asymptomatic and sometimes naturally disappearing course of the disease in older children, EOS is progressive and in many cases causes severe complications, such as blindness, joint destruction, and visceral involvement.
Blau syndrome (BS; 186580), which also shows early-onset granulomatous arthritis, uveitis, and skin rash, is a rare familial disorder transmitted in an autosomal dominant manner. By linkage analysis, the responsible locus was mapped to chromosome 16, and the ... Blau syndrome (BS; 186580), which also shows early-onset granulomatous arthritis, uveitis, and skin rash, is a rare familial disorder transmitted in an autosomal dominant manner. By linkage analysis, the responsible locus was mapped to chromosome 16, and the CARD15 gene was identified as the susceptibility gene. Since the first report of Blau syndrome, there has been discussion of whether EOS and BS are the same disease. In the first paper describing mutations in the CARD15 gene in patients with BS, Miceli-Richard et al. (2001) found no CARD15 mutation in 2 EOS patients. However, Kanazawa et al. (2004) described a sporadic case of systemic granulomatosis syndrome with clinical features of EOS that showed the same CARD15 mutation as detected in BS. Kanazawa et al. (2005) collected Japanese EOS cases retrospectively and searched for CARD15 mutations. Among 10 such cases, heterozygous missense mutations were found in 9; 4 showed an arg334-to-trp mutation (605956.0006) that had been reported in BS, 4 showed novel missense mutations, and 1 showed compound heterozygosity for 2 different missense mutations. All 6 of these variants of CARD15 showed increased basal NF-kappa-B (see NFKB1; 164011) activity. Kanazawa et al. (2005) concluded that the majority of early-onset sarcoidosis and Blau syndrome cases share a common genetic etiology of CARD15 mutations that cause constitutive NF-kappa-B activation.