Author information

1 SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.

2 Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Institute for Medical Science and Biochemistry, University of Toronto, Hospital for Sick Children,Toronto, Ontario, Canada.

Abstract

PURPOSE OF REVIEW: To summarize the current understanding and recent advances on the genetic aetiology in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD).

RECENT FINDINGS: IBD is a chronic disorder of the gastrointestinal tract whose manifestation is a result of complex interactions between genetics, environment, immune system and microbial flora. Over 230 IBD risk loci have been reported in genome wide association studies but the genetic contribution of the majority of these loci in the manifestation of IBD is very low. Patients with VEO-IBD present with a more severe disease than older patients, characterized by poor prognosis and failure of conventional therapy. Recent studies have reported several monogenic diseases with high penetrance that present with IBD and IBD-like intestinal manifestations and overlap with primary immunodeficiencies. Increasing body of evidence supports a prominent role of genetics in the onset of VEO-IBD. New genetic variants and diagnoses in VEO-IBD are reviewed and current challenges in therapy with potential strategy to manage the disease are discussed.

SUMMARY: Functional analysis of the genes implicated in monogenic IBD has increased the understanding of the underlying pathobiological mechanism of the disease. This knowledge can be used to personalize medicine for specific patients, improving the standard of care and quality of life.