Kammermeier, J;
Dziubak, R;
Pescarin, M;
Drury, S;
Godwin, H;
Reeve, K;
Chadokufa, S;
... Shah, N; + view all
(2017)
Phenotypic and genotypic characterisation of inflammatory bowel disease presenting before the age of 2 years.
Journal of Crohn's and Colitis
, 11
(1)
pp. 60-69.
10.1093/ecco-jcc/jjw118.
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Abstract
OBJECTIVES: Inflammatory bowel disease 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 two years and establish phenotypic features associated with underlying monogenicity. METHODS: Phenotype data of 62 children with disease-onset before the age of two years presenting over the last 20 years were reviewed. Children without previously established genetic diagnosis were prospectively recruited for next-generation sequencing. RESULTS: 62 patients (55% male) were identified. The median disease-onset was three months of age [IQR: 1 to 11]. Conventional IBD classification only applied to 15 patients with Crohn's disease-like (24%) and three with ulcerative colitis-like (5%) phenotype. Forty-four patients (71%) were diagnosed with otherwise unclassifiable IBD. Patients frequently required parenteral nutrition (40%), extensive immunosuppression (31%), hematopoietic 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 6(th) month of life, stunting, extensive intestinal disease and histological evidence of epithelial abnormalities. CONCLUSION: IBD in children with disease-onset before the age of two 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.
| Type: | Article |
|---|---|
| Title: | Phenotypic and genotypic characterisation of inflammatory bowel disease presenting before the age of 2 years |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/ecco-jcc/jjw118 |
| Publisher version: | http://dx.doi.org/10.1093/ecco-jcc/jjw118 |
| Language: | English |
| Additional information: | This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Crohn's and Colitis following peer review. The version of record [Kammermeier, J; Dziubak, R; Pescarin, M; Drury, S; Godwin, H; Reeve, K; Chadokufa, S; (2017) Phenotypic and genotypic characterisation of inflammatory bowel disease presenting before the age of two years. Journal of Crohn's and Colitis , 11 (1) pp. 60-69.] is available online at: https://doi.org/10.1093/ecco-jcc/jjw118. |
| Keywords: | Inflammatory bowel disease, infantile-onset, genetics, next-generation sequencing, phenotype, immunodeficiency, paediatrics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1499806 |
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