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Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years
Jochen Kammermeier1,2, Robert Dziubak2, Matilde Pescarin2
1Genetics and Genomic Medicine, Institute of Child Health, University College London, London, UK j.kammermeier@ucl.ac.uk.
Insights
Early-onset inflammatory bowel disease [IBD] in children under two is often unclassifiable. Monogenic causes are frequent, presenting with distinct features like early onset and growth stunting.
Area of Science:
- Pediatric Gastroenterology
- Clinical Genetics
- Immunology
Background:
- Inflammatory bowel disease [IBD] presenting in early childhood is rare.
- Identifying monogenic forms of IBD is crucial for early diagnosis and management.
Purpose of the Study:
- To describe phenotypes and genotypes of patients with IBD presenting before age 2.
- To establish phenotypic features associated with monogenic IBD.
Main Methods:
- Retrospective review of 62 children with IBD onset before age 2.
- Prospective next-generation sequencing for genetic diagnosis in eligible patients.
Main Results:
- 71% of patients had unclassifiable IBD; only 24% had Crohn's disease-like and 5% ulcerative colitis-like phenotypes.
- 31% of patients had an underlying monogenic disease identified.
- Features associated with monogenic IBD included consanguinity, onset before 6 months, stunting, and extensive intestinal disease.
Conclusions:
- IBD in very young children is frequently unclassifiable and treatment-resistant.
- Monogenic diseases can present with an IBD-like phenotype, making them indistinguishable in some cases.
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.
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