The role of monogenic disease in children with very early onset inflammatory bowel disease

Abstract

Purpose of Review Inflammatory bowel disease (IBD) is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as Very Early Onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions. Recent Findings VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression and poor response to most conventional therapies. This article will review the advances in sequencing technology that have led to identification of novel gene variants associated with disease and potentially new targeted therapeutic options. Summary Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. Identification of the causal gene or pathways these children may allow for true precision medicine with targeted therapy and improved disease course.

Very early‐onset inflammatory bowel disease in Japan: A nationwide survey

“…A genetic diagnosis is particularly important because some monogenic IBD cases have been reported as curable by hematopoietic stem cell transplantation 2,14,15 . It has been recommended that comprehensive gene analysis, such as whole‐exome sequencing and, in some cases, whole‐genome sequencing, should be conducted 2,15–21 . These comprehensive approaches have enabled the detection of novel gene mutations such as NOX1 , COL7A1 , and LAMB1 22,23 .…”

“…2,14,15 It has been recommended that comprehensive gene analysis, such as whole-exome sequencing and, in some cases, whole-genome sequencing, should be conducted. 2,[15][16][17][18][19][20][21] These comprehensive approaches have enabled the detection of novel gene mutations such as NOX1, COL7A1, and LAMB1. 22,23 Recently, screening tests using gene panels and microarray chips that aggregate candidate genes for gene mutations obtained from comprehensive gene analysis have also been reported.…”

Magnetic resonance colonography with intestine-absorbable nanoparticle contrast agents in evaluation of colorectal inflammation

“…An important factor in the pathogenesis of IBD is the accumulation of phagocytes such as macrophages and dendritic cells in the intestinal wall. Some studies have shown the destruction of that the epithelial cell-to-cell junction protein in the intestinal wall of patients with IBD [33][34][35][36][37][38]. Therefore, the phagocytosis of macrophages and the destruction of intercellular linkers may be the main mechanism by which nanomaterials enter the intercellular space.…”

Neonatal Crohn’s disease with Oral ulcer as the first symptom caused by a compound heterozygote mutation in IL-10RA: a case report

“…In IBD cases, CD is more common in children, but ulcerative colitis is more common in adults [14]. The prevalence of CD is 30–35% in children with very early inflammatory bowel disease (VIBD) [15].…”