Expansion of Phenotypic and Genotypic Spectrum in Yao Syndrome: A Case Series.

Abstract

Yao syndrome (YAOS; OMIM 617321) was formerly termed nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-associated autoinflammatory disease. This study sought to report novel findings related to this disease. A medical records review analysis of a case series was conducted, and all patients fulfilled the diagnostic criteria for YAOS and underwent comprehensive diagnostic workups, including molecular genotyping of blood specimens for periodic fever syndromes and NOD2-associated disease. A total of 11 patients with YAOS were analyzed, and all were Whites with a median age of 25.9 years at disease onset. All patients shared the similar autoinflammatory phenotype of YAOS. Among the 11 patients, we identified 7 patients who had the known phenotype of YAOS, as well as recurring and brief eyelid swelling with or without eyelid discoloration or conjunctivitis. Molecular analysis of blood cells using periodic fever gene panel has identified the presence of NOD2 variants in all 11 patients. Apart from the known YAOS-associated common NOD2 genotype, 5 novel and unknown significance NOD2 variants were identified in patients who presented with typical phenotype of YAOS. This study provides novel clinical and molecular data for YAOS and supports the expansion of the phenotypic and genotypic spectrum of the disease.