Inflammatory bowel disease (IBD) [45 genes]

Inflammatory bowel disease (IBD) groups a heterogeneous set of chronic inflammatory disorders that affect the gastrointestinal tract. There are three main phenotypes in this group including Crohn’s disease (CD), ulcerative colitis (UC), and unclassified IBD. Alterations in the intestinal microbiota, environmental factors, and immunological or genetic defects (deregulation of Th lymphocytes, failures in cellular autophagy processes, or alteration of inflammatory signals) are associated with the development of IBD. Although it usually appears in young adults, cases of early onset during childhood or the neonatal state are also common, characterized by more severe phenotypes. It is estimated that 25%-30% of pediatric IBD cases have a positive family history, suggesting the existence of a variable hereditary component that would support the indication of a genetic study.

• Diarrhea
• Bowel inflammation
• Multisystem abnormalities
• Intestinal villous atrophy
• Eosinophilia of the mucosa

• Uknown (monogenic forms)
• ~1/1,000 (CD)
• ~1/1,000 (UC)

• Diagnosis and genetic counseling
• Monoclonal antibodies against IL-12
• Immunomodulators
• Anti-inflammatories

Genetic study would NOT be indicated in all cases of IBD, so it is important to select those patients with a high suspicion of a genetic cause who can benefit from a conclusive result. The identification of genetic variants causing the disease is useful in terms of accurate disease diagnosis and genetic counseling.

The multifactorial origin of IBD suggests that the genetic component would be another risk factor, along with other external agents, so any genetic finding in susceptibility genes should not be treated in the same way as findings in genes responsible for monogenic forms. A small percentage of cases cause severe IBD, mainly with recessive inheritance and manifestations from early childhood. On the other hand, there are some forms of the disease, associated with or secondary to, other pathologies, such as certain primary immunodeficiencies.