Ryusuke Nambu1, Neil Warner2, Daniel J Mulder2, Daniel Kotlarz3, Dermot P B McGovern4, Judy Cho5, Christoph Klein3, Scott B Snapper6, Anne M Griffiths7, Itaru Iwama8, Aleixo M Muise9. 1. SickKids Inflammatory Bowel Disease Centre, Hospital for Sick Children, Toronto, Canada; Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Canada; Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan. 2. SickKids Inflammatory Bowel Disease Centre, Hospital for Sick Children, Toronto, Canada; Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Canada. 3. Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. 4. F. Widjaja Foundation Inflammatory Bowel Disease Center, Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California. 5. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York, New York. 6. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts. 7. SickKids Inflammatory Bowel Disease Centre, Hospital for Sick Children, Toronto, Canada; Department of Pediatrics, Institute of Medical Science and Biochemistry, University of Toronto, Hospital for Sick Children, Toronto, Canada. 8. Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan. 9. SickKids Inflammatory Bowel Disease Centre, Hospital for Sick Children, Toronto, Canada; Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Canada; Department of Pediatrics, Institute of Medical Science and Biochemistry, University of Toronto, Hospital for Sick Children, Toronto, Canada. Electronic address: aleixo.muise@utoronto.ca.
Abstract
BACKGROUND & AIMS: Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine the clinical features, genetic profile, and previously used treatment strategies in monogenic IBD. METHODS: A systematic review of MEDLINE articles published between January 2000 and December 2020 was conducted. A total of 750 individual monogenic IBD cases were identified from 303 eligible articles. RESULTS: The most frequently reported monogenic IBD genes were IL10RA/B, XIAP, CYBB, LRBA, and TTC7A. In total, 63.4% of patients developed IBD before 6 years of age, 17.4% developed IBD between ages 10 and 17.9 years, and 10.9% developed IBD after age 18. There was a substantial difference between these age groups and the underlying monogenic disorders. Only 31.7% had any history of extraintestinal comorbidity (EIC) before IBD onset, but 76.0% developed at least 1 EIC during their clinical course. The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%). Bowel surgery, biologic therapy, and hematopoietic stem cell transplantation were performed in 27.1%, 32.9%, and 23.1% of patients, respectively. CONCLUSIONS: Monogenic IBD cases, although rare, have varied extraintestinal comorbidities and limited treatment options including surgery and transplant. Early identification and improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is important for effective management.
BACKGROUND & AIMS: Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine the clinical features, genetic profile, and previously used treatment strategies in monogenic IBD. METHODS: A systematic review of MEDLINE articles published between January 2000 and December 2020 was conducted. A total of 750 individual monogenic IBD cases were identified from 303 eligible articles. RESULTS: The most frequently reported monogenic IBD genes were IL10RA/B, XIAP, CYBB, LRBA, and TTC7A. In total, 63.4% of patients developed IBD before 6 years of age, 17.4% developed IBD between ages 10 and 17.9 years, and 10.9% developed IBD after age 18. There was a substantial difference between these age groups and the underlying monogenic disorders. Only 31.7% had any history of extraintestinal comorbidity (EIC) before IBD onset, but 76.0% developed at least 1 EIC during their clinical course. The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%). Bowel surgery, biologic therapy, and hematopoietic stem cell transplantation were performed in 27.1%, 32.9%, and 23.1% of patients, respectively. CONCLUSIONS: Monogenic IBD cases, although rare, have varied extraintestinal comorbidities and limited treatment options including surgery and transplant. Early identification and improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is important for effective management.
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