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.
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.
Authors: Masanobu Tsuda; Troy R Torgerson; Carlo Selmi; Eleonora Gambineri; Magda Carneiro-Sampaio; Sara Ciullini Mannurita; Patrick S C Leung; Gary L Norman; M Eric Gershwin Journal: J Autoimmun Date: 2010-07-22 Impact factor: 7.094
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Authors: Tiffanie T Tse; Amy S Chan; Rosemary G Moodie; Yousef Etoom; Carol A Durno; Aleixo M Muise; Peter D Wong Journal: Paediatr Child Health Date: 2019-03-14 Impact factor: 2.253
Authors: Alina Kurolap; Orly Eshach Adiv; Liza Konnikova; Lael Werner; Claudia Gonzaga-Jauregui; Maya Steinberg; Vanessa Mitsialis; Adi Mory; Moran Y Nunberg; Sarah Wall; Ron Shaoul; John D Overton; Alan R Shuldiner; Yaniv Zohar; Tamar Paperna; Scott B Snapper; Dror S Shouval; Hagit Baris Feldman Journal: J Clin Immunol Date: 2019-05-11 Impact factor: 8.317