J Pediatr Gastroenterol Nutr. 2021 Mar 1;72(3):456-473. doi: 10.1097/MPG.0000000000003017.

Holm H Uhlig ^1 2 3, Fabienne Charbit-Henrion ⁴, Daniel Kotlarz ⁵, Dror S Shouval ⁶, Tobias Schwerd ⁵, Caterina Strisciuglio ⁷, Lissy de Ridder ⁸, Johan van Limbergen ⁹, Marina Macchi ¹, Scott B Snapper ¹⁰, Frank M Ruemmele ¹¹, David C Wilson ¹², Simon P L Travis ^1 3, Anne M Griffiths ^13 14 15, Dan Turner ¹⁶, Christoph Klein ⁵, Aleixo M Muise ^13 14 15, Richard K Russell ¹², Paediatric IBD Porto group of ESPGHAN

Author information

• ¹Translational Gastroenterology Unit.
• ²Department of Pediatrics.
• ³Biomedical Research Center, University of Oxford, Oxford, United Kingdom.
• ⁴Université de Paris, INSERM UMR 1163 Immunité Intestinale, APHP, Hôpital Necker Enfants Malades, Service de Génétique moléculaire, Paris, France.
• ⁵Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
• ⁶Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
• ⁷Paediatric Gastroenterology, University Federico II, Naples, Italy.
• ⁸Department of Paediatric Gastroenterology, Erasmus University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands.
• ⁹Amsterdam University Medical Centres, Emma Children's Hospital, The Netherlands and Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
• ¹⁰Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
• ¹¹Université de Paris, APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France.
• ¹²Child Life and Health, University of Edinburgh, Department of Paediatric Gastroenterology, The Royal Hospital for Sick Children, Edinburgh.
• ¹³The Hospital for Sick Children, University of Toronto.
• ¹⁴SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, The Hospital for Sick Children.
• ¹⁵Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Toronto, Ontario, Canada.
• ¹⁶Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.

Abstract

Background: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups.

Methods: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists).

Results: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries.

Conclusions: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD.