Clinical Genomics for the Diagnosis of Monogenic Forms of Inflammatory Bowel Disease: A Position Paper From the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

Scott B Snapper, Richard K Russell, Aleixo M Muise, Christoph Klein, Dan Turner, Anne M Griffiths, Simon P L Travis, David C Wilson, Frank M Ruemmele, Holm H Uhlig, Marina Macchi, Johan van Limbergen, Lissy de Ridder, Caterina Strisciuglio, Tobias Schwerd, Dror S Shouval, Daniel Kotlarz, Fabienne Charbit-Henrion

Journal: Journal of pediatric gastroenterology and nutrition 2021;72(3):456-473

PMID: 33346580

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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.

Address: Translational Gastroenterology Unit.; Department of Pediatrics.; Biomedical Research Center, University of Oxford, Oxford, United Kingdom.; Université de Paris, INSERM UMR 1163 Immunité Intestinale, APHP, Hôpital Necker Enfants Malades, Service de Génétique moléculaire, Paris, France.; Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Pediatric 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.; Paediatric Gastroenterology, University Federico II, Naples, Italy.; Department of Paediatric Gastroenterology, Erasmus University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands.; Amsterdam 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.; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Université de Paris, APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France.; Child Life and Health, University of Edinburgh, Department of Paediatric Gastroenterology, The Royal Hospital for Sick Children, Edinburgh.; The Hospital for Sick Children, University of Toronto.; SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, The Hospital for Sick Children.; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Toronto, Ontario, Canada.; Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.

DOI: 10.1097/MPG.0000000000003017

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MeSH Terms: Child, Child Nutritional Physiological Phenomena, Colitis, Gastroenterology, Genomics, Humans, Inflammatory Bowel Diseases