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Monogenic inflammatory bowel disease (IBD) refers to a diverse spectrum of rare genetic disorders that present with intestinal inflammation.1 The majority of patients with monogenic IBD, unlike those with polygenic IBD, show symptoms before the age of six. Additionally, because monogenic and polygenic IBD can have indistinguishable endoscopic or histologic features, establishing an accurate diagnosis via traditional methods remains a challenge.2

Signs That Should Raise Suspicion of Monogenic IBD and Prompt Testing

  • Onset at age of 6 or younger
    • The younger the patient, the higher the suspicion of a monogenic disorder
    • Up to 15% of patients with IBD presenting before the age of 6 may have a monogenic disorder2
  • Frequent infections
  • Overt skin manifestations (e.g., eczema, granulomas, cutaneous vasculitis)
  • Dysmorphism
  • Hair abnormalities
  • Refractory disease or does not respond to conventional IBD treatment
Age of symptom-onset for IBD-associated monogenic disorders3
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Comprehensive Testing from Mayo Clinic Laboratories to Confirm Diagnosis and Optimize Treatment

Genetic testing can identify patients with monogenic IBD and primary immunodeficiencies that present with IBD-like features. Depending on the genetic cause of the disease, clinicians can use the results to guide treatment decisions and improve patient outcomes.

Mayo Clinic Laboratories offers a genetic panel to identify variants in 51 genes with established genetic associations with monogenic IBD and primary immunodeficiencies that present with IBD-like features.

View the list of included genes and their monogenic IBD-associated disorders.

Billing and Prior Authorization Services: On behalf of our clients, Mayo Clinic Laboratories will seek insurance authorization for this testing and file an insurance claim upon final result. Learn more.

Interpretations in the Context of Patient Phenotype

Genetic testing is probabilistic in nature, which makes variant classification and interpretation challenging. Although guidelines with specific criteria are used, professional judgement is required to determine whether a detected variant is the cause of the patient’s phenotype.

Your patient’s results are interpreted by a team of experienced laboratory directors and genetic counselors who are familiar with the latest literature and will classify the variants detected using the American College of Medical Genetics and Genomics/Association for Molecular Pathology Guidelines.

Access to Mayo Clinic Experts

Extend your network to include world-renowned experts. Our clinicians, laboratory directors, and genetic counselors are available to directly discuss results in context of the patient’s presentation and clinical history.

Additionally, we know there will likely be questions about clinical next steps after a positive result. To help with this, Mayo Clinic experts are available for discussion, when necessary.

For Clinical or Technical Support Contact Our Specialists
at 855-516-8404 or 1-855-379-3115 (International)

IBD-Associated Monogenic Disorders and Their Linked Genes

Epithelial Barrier

  • X-linked ectodermal immunodeficiency
    (IKBKG)
  • TTC7A deficiency
    (TTC7A)
  • ADAM17 deficiency
    (ADAM17)

Immune Dysregulation

  • IPEX/IPEX-like
    (FOXP3, IL2RA, STAT1)
  • IL10-signaling defects
    (IL10RA, IL10RB, IL10)
  • CTLA4 haploinsufficiency with autoimmune infiltration
    (CTLA4)

T- and B-Cell Defects

  • Common variable immunodeficiency
    (LRBA, ICOS)
  • IL-21 deficiency
    (IL21)
  • Agammaglobulinemia
    (BTK, PIK3R1)
  • Hyper IgM syndrome
    (CD40LG, AICDA)
  • Hyper IgE syndrome
    (DOCK8)
  • Wiskott-Aldrich syndrome
    (WAS, WIPF1)
  • Omenn syndrome/SCID
    (DCLRE1C, ZAP70, RAG2, IL2RG, LIG4, ADA, CD3γ)
  • Hoyeraal-Hreidarsson syndrome
    (DKC1, RTEL1)

Hyperinflammatory and Autoinflammatory Disorders

  • Mevalonate kinase deficiency
    (MVK)
  • Phospholipase C-γ2 defects
    (PLCG2)
  • Familial Mediterranean fever
    (MEFV)
  • Familial hemophagocytic lymphohistiocytosis
    (STXBP2)
  • X-linked lymphoproliferative syndrome
    (XIAP, SH2D1A)

Phagocyte Defects

  • Chronic granulomatous disease
    (CYBB, CYBA, NCF2, NCF4)
  • Glycogen storage disease
    (SLC37A4)
  • Congenital neutropenia
    (G6PC3)
  • Leukocyte adhesion deficiency
    (ITGB2)

Additional Genes Associated with IBD-Like Monogenic Diseases

  • MASP deficiency
    (MASP2)
  • Trichohepatoenteric syndrome
    (SKIV2L, TTC37)

Additional Resources

References

1. Shim, Jung. Recent advances in very early onset inflammatory bowel disease. Pediatr Gastroenterol Hepatol Nutr. 2019;21(1):41–49.

2. Lega S, Pin A, Arrigo S, Cifaldi C, Girardelli M, et al. Diagnostic approach to monogenic inflammatory bowel disease in clinical practice: a ten-year multicentric experience. Inflamm Bowel Dis. 2019;20(20):1-8.

3. Uhlig HH, Schewrd T, Koletzko S, et al. The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease. Gastroenterology. 2014;147(5):990-1007.e3.

Mayo Clinic Laboratories

Mayo Clinic Laboratories

This post was authored by the Marketing Team at Mayo Clinic Laboratories.