Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years
| Autor: | Chiara Bacchelli, Kate Reeve, Marco Gasparetto, Heather Godwin, Suzanne Drury, Nikki Acton, Gabi Noble-Jamieson, S. Chadokufa, Holm H. Uhlig, Chela James, Sara Sider, B. Huggett, Matilde Pescarin, Elena Cernat, Jochen Kammermeier, Neil Shah, Robert Dziubak, PL Beales, Kimberly Gilmour, Neil J. Sebire, Mamoun Elawad, Fevronia Kiparissi |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty medicine.medical_treatment Disease Hematopoietic stem cell transplantation Inflammatory bowel disease Gastroenterology Endoscopy Gastrointestinal 03 medical and health sciences 0302 clinical medicine Crohn Disease Interquartile range Internal medicine medicine Humans Genetic Testing Age of Onset Immunodeficiency business.industry Infant General Medicine Inflammatory Bowel Diseases medicine.disease Ulcerative colitis digestive system diseases Intestines Transplantation Phenotype 030104 developmental biology Immunology Original Article Colitis Ulcerative Female 030211 gastroenterology & hepatology Age of onset business |
| Zdroj: | Journal of Crohn's and Colitis. 11:60-69 |
| ISSN: | 1876-4479 1873-9946 |
| Popis: | Objectives: Inflammatory bowel disease [IBD] presenting in early childhood is extremely rare. More recently, progress has been made to identify children with monogenic forms of IBD predominantly presenting very early in life. In this study, we describe the heterogeneous phenotypes and genotypes of patients with IBD presenting before the age of 2 years and establish phenotypic features associated with underlying monogenicity. Methods: Phenotype data of 62 children with disease onset before the age of 2 years presenting over the past 20 years were reviewed. Children without previously established genetic diagnosis were prospectively recruited for next-generation sequencing. Results: In all, 62 patients [55% male] were identified. The median disease onset was 3 months of age (interquartile range [IQR]: 1 to 11). Conventional IBD classification only applied to 15 patients with Crohn’s disease [CD]-like [24%] and three with ulcerative colitis [UC]-like [5%] phenotype; 44 patients [71%] were diagnosed with otherwise unclassifiable IBD. Patients frequently required parenteral nutrition [40%], extensive immunosuppression [31%], haematopoietic stem-cell transplantation [29%], and abdominal surgery [19%]. In 31% of patients, underlying monogenic diseases were established [ EPCAM, IL10, IL10RA, IL10RB, FOXP3, LRBA, SKIV2L, TTC37, TTC7A ]. Phenotypic features significantly more prevalent in monogenic IBD were: consanguinity, disease onset before the 6th month of life, stunting, extensive intestinal disease and histological evidence of epithelial abnormalities. Conclusions: IBD in children with disease onset before the age of 2 years is frequently unclassifiable into Crohn’s disease and ulcerative colitis, particularly treatment resistant, and can be indistinguishable from monogenic diseases with IBD-like phenotype. |
| Databáze: | OpenAIRE |
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