Blau Syndrome-Associated Uveitis and the NOD2 Gene

Blau syndrome (BS), a rare autosomal dominant autoinflammatory syndrome, is an example of a monogenic disease. It was first described as a classic triad of uveitis, arthritis, and exanthema, typically seen in patients less than four years of age. Since that time, the phenotype has been expanded to include fever, cranial neuropathies, cardiovascular abnormalities, and granulomas of the liver and kidney. The ocular inflammation is often a panuveitis that occurs later in the disease course and typically carries the greatest morbidity in BS. BS has been mapped to the chromosomal region 16q12-21, also known as the NOD2 gene (formerly CARD15/NOD2). The disease is secondary to a single amino acid mutation NOD2 that leads to peptidoglycan-independent activity of nuclear factor (NF)-kappa B. Clinical and genetic aspects of BS will be discussed, as well as recent advances in treatment protocols.