Clinical Phenotypes and Genetic Findings in Very-Early-Onset Inflammatory Bowel Disease: A Vietnamese Pediatric Cohort Study.

Background/

Objectives

Very early onset inflammatory bowel disease (VEO-IBD), frequently associated with monogenic defects, is increasingly recognized worldwide but remains poorly characterized in Vietnam. This study aimed to characterize the clinical phenotypes and genetic spectrum of Vietnamese children with VEO-IBD.

Methods

We conducted a retrospective cohort study at a tertiary pediatric referral center in Vietnam from July 2016 to January 2026. Clinical, laboratory, endoscopic, histopathological, genetic, and treatment data were systematically collected and analyzed. Monogenic variants were identified using next-generation sequencing and classified according to ACMG criteria.

Results

Thirty-six children were included, with a median age at onset of 7.5 months, and 72.2% presenting before 24 months. Crohn's disease predominated (72.2%). Disease burden was high, with growth impairment in 75.0% and anemia in 91.7%. Extraintestinal manifestations were frequent, particularly recurrent infections (72.2%), dermatitis (44.4%), and oral ulcers (44.4%). Perianal disease occurred in 58.3%, with early complications including perianal ulcer (44.4%), perianal abscess (30.6%) and fistulas (33.3%). Inflammatory markers were markedly elevated, and disease activity indices indicated moderate-to-severe disease at diagnosis. Genetic testing was performed in 91.7% of patients, identifying monogenic etiologies in 30.3%. Identified variants involved genes related to immune regulation (IL10RA/IL10RB, FOXP3, XIAP), autoinflammation (TNFAIP3), host defense (CYBB), and epithelial function (MYO5B).

Conclusions

Monogenic etiologies account for a substantial proportion of VEO-IBD and are associated with distinct clinical phenotypes and therapeutic implications. Early integration of genomic testing with clinical phenotyping is essential to improve diagnostic precision and enable pathway-based treatment, supporting precision medicine in pediatric IBD.