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

Sara Lega, Alessia Pin, Serena Arrigo, Cristina Cifaldi, Martina Girardelli, Anna Monica Bianco, Monica Malamisura, Giulia Angelino, Simona Faraci, Francesca Rea, Erminia Francesca Romeo, Marina Aloi, Claudio Romano, Arrigo Barabino, Stefano Martelossi, Alberto Tommasini, Gigliola Di Matteo, Caterina Cancrini, Paola De Angelis, Andrea FinocchiMatteo 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.
Original languageEnglish
Pages (from-to)izz178
JournalInflammatory Bowel Diseases
Publication statusPublished - Aug 3 2019


  • monogenic IBD
  • next generation sequencing
  • very early onset IBD


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