Methods: Genetic analysis of RAG-1, RAG-2, and DCLRE1C was performed. Written permission was obtained from parents for use of photographs and clinical history.
Results: This patient presented at the age of 12 months with a generalized erythematous rash after receiving the varicella vaccine. He had been previously healthy until this time with no history of recurrent infections, diarrhea, or failure to thrive. Laboratory findings revealed non-protective levels of pneumococcal and diphtheria serotypes despite immunization, elevated IgE, poor T-cell mitogen and antigen response, low T cell numbers, and normal levels of B cells. Gene analysis revealed sequence variations associated with OS in both the RAG-2 (homozygous 1352G>C) and DCLRE1C (heterozygous 901A>G) genes, and gene rearrangement studies showed oligoclonal T cell receptor rearrangements. This patient was determined to have incomplete OS and was successfully treated with hematopoietic stem cell transplantation.
Conclusions: We present this patient as a case of incomplete Omenn’s syndrome presenting with a combination of mutations in RAG-2 and DCLRE1C that has not been previously described, which led to a novel phenotype of late clinical presentation and incomplete OS. Further research is necessary to determine the precise role of each mutation, particularly in regards to the clinical presentation. Discovery of this new phenotype has direct diagnostic implications, and with more detailed studies, prognostic and therapeutic correlations may too be revealed.