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J Crohns Colitis. 2017 Jan;11(1):60-69. doi: 10.1093/ecco-jcc/jjw118. Epub 2016 Jun 14.

Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years.

Author information

1
Genetics and Genomic Medicine, Institute of Child Health, University College London, London, UK j.kammermeier@ucl.ac.uk.
2
Department of Gastroenterology, Great Ormond Street Hospital, London, UK.
3
Genetics and Genomic Medicine, Institute of Child Health, University College London, London, UK.
4
NE Thames Regional Genetics Laboratory, Great Ormond Street Hospital, London, UK.
5
Department of Paediatric Gastroenterology, Addenbrookes Hospital, Cambridge, UK.
6
Department of Histopathology, Great Ormond Street Hospital, London, UK.
7
Department of Immunology, Great Ormond Street Hospital, London, UK.
8
Transitional Gastroenterology Unit, Nuffield Department of Medicine and Department of Paediatrics, University of Oxford, UK.

Abstract

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.

KEYWORDS:

Inflammatory bowel disease; genetics; immunodeficiency; infantile-onset; next-generation sequencing; paediatrics; phenotype

PMID:
27302973
PMCID:
PMC5885808
DOI:
10.1093/ecco-jcc/jjw118
[Indexed for MEDLINE]
Free PMC Article

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