Two Chinese pedigrees of Blau syndrome with thirteen affected members

Blau syndrome (BS) is a rare autosomal dominant autoinflammatory disease characterized by the clinical triad of dermatitis, arthritis, and uveitis. It is caused by mutations in nucleotide-binding oligomerization domain-containing protein-2 (NOD2) gene. BS has been widely reported in Caucasians but cases documented in China are scarce. We reported two Chinese families with BS, which were by far the two largest pedigrees in the Chinese population. We identified two unrelated families with BS. The phenotypes and genotypes of these patients were reviewed and compared with previous cohorts. The proband of the first family was a 32-year-old Chinese Han woman, who had dermatitis, polyarthritis, and intermittent fever since the age of 6, bilateral panuveitis since 12. During her disease course, she lost her vision and developed hand flexion contractures. The proband of the second family was a 36-year-old Chinese Han woman, who had dermatitis and bilateral panuveitis since the age of 7, persistent polyarthritis since 13. Additional 7 and 4 family members were affected in the first and second families, respectively, and pedigree analysis suggested autosomal dominant inheritance. Genetic testing in both families identified the heterozygous c.1000 C > T, R334W mutation in NOD2 gene. Only one patient had recurrent fever as an expanded manifestation beyond the classical triad. BS can occur in multiple ethnic groups including the Chinese Han population. Our 11 adult patients constituted the largest adult cohort of BS ever reported in China. Lack of recognition of BS led to a significant delay in diagnosis. A considerable percentage of patients did not demonstrate the full spectrum of the classical triad, further complicating the diagnosis.