PURPOSE OF REVIEW:
Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease.
The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.