Differences between adults and children: genetics and beyond

Abstract

Clinical observations and epidemiological studies have highlighted some important differences in disease course and phenotypes between pediatric inflammatory bowel disease (IBD) and adult-onset IBD. Also from a therapeutic angle, the approach to young-onset IBD is different with a more rapid introduction of azathioprine and a high threshold for long and systemic steroid use, which may affect bone mineral density and growth. The observed clinical differences have been an area of scientific research and genetic studies have been the focus of attention. Specific candidate gene studies as well as genome-wide association studies have been performed in pediatric IBD. With the exception of very early-onset IBD occurring before the age of 2 years; no overt differences in genetic susceptibility have been identified. In contrast, very early-onset IBD seems in particular to be a genetic disease with defects in the IL10 signaling pathway being the principal example. This review aims to answer some straightforward questions arising in this topic by giving concise information.

Keywords:

• Crohn’s disease
• genetics
• genome-wide association studies
• IL-10R mutations
• inflammatory bowel disease
• ulcerative colitis
• very early-onset IBD

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The natural course and phenotype of pediatric inflammatory bowel disease (IBD) differs from adult-onset IBD.

• Specific candidate gene studies as well as genome-wide association studies failed to convincingly show specific genes underlying pediatric IBD.

• Very early-onset IBD should, however, be seen as a separate entity with a Mendelian type of inheritance and often by defects in the IL10 signaling pathway.

• Novel techniques as exome sequencing have shown to facilitate a molecular diagnosis in very young patients with suspected severe IBD.

• The identified mutations in very early-onset IBD illustrate how modern genetic technologies are introduced in the clinic in a very meaningful way.