Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience: Inflammatory Bowel Diseases

S. Lega, A. Pin, S. Arrigo, C. Cifaldi, M. Girardelli, A.M. Bianco, M. Malamisura, G. Angelino, S. Faraci, F. Rea, E.F. Romeo, M. Aloi, C. Romano, A. Barabino, S. Martelossi, A. Tommasini, G. DI Matteo, C. Cancrini, P. De Angelis, A. FinocchiM. Bramuzzo

Research output: Contribution to journalArticlepeer-review


Background and aims: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. Methods: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected. Results: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. Conclusion: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes. © 2019 Crohn's & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Original languageEnglish
Pages (from-to)720-727
Number of pages8
JournalInflammatory Bowel Dis.
Issue number5
Publication statusPublished - 2020


  • monogenic IBD
  • next generation sequencing
  • very early onset IBD
  • Article
  • bone marrow transplantation
  • clinical feature
  • clinical practice
  • cohort analysis
  • diagnostic approach route
  • diagnostic test accuracy study
  • disease severity
  • endoscopy
  • female
  • genetic variability
  • high throughput sequencing
  • human
  • inflammatory bowel disease
  • laboratory test
  • major clinical study
  • male
  • monogenic disorder
  • observational study
  • onset age
  • patient care
  • patient information
  • phenotype
  • priority journal


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