Kammermeier Jochen, Dziubak Robert, Pescarin Matilde, Drury Suzanne, Godwin Heather, Reeve Kate, Chadokufa Sibongile, Huggett Bonita, Sider Sara, James Chela, Acton Nikki, Cernat Elena, Gasparetto Marco, Noble-Jamieson Gabi, Kiparissi Fevronia, Elawad Mamoun, Beales Phil L, Sebire Neil J, Gilmour Kimberly, Uhlig Holm H, Bacchelli Chiara, Shah Neil
Genetics and Genomic Medicine, Institute of Child Health, University College London, London, UK
Department of Gastroenterology, Great Ormond Street Hospital, London, UK.
J Crohns Colitis. 2017 Jan;11(1):60-69. doi: 10.1093/ecco-jcc/jjw118. Epub 2016 Jun 14.
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.
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.
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.
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.
儿童期早期出现的炎症性肠病（IBD）极为罕见。最近，在识别主要在生命早期出现的单基因形式IBD患儿方面取得了进展。在本研究中，我们描述了2岁前发病的IBD患者的异质表型和基因型，并确定与潜在单基因性相关的表型特征。
回顾了过去20年中62例2岁前发病儿童的表型数据。对先前未确诊的儿童进行前瞻性招募以进行下一代测序。
共识别出62例患者（55%为男性）。疾病发病的中位年龄为3个月（四分位间距[IQR]：1至11个月）。传统的IBD分类仅适用于15例克罗恩病（CD）样患者（24%）和3例溃疡性结肠炎（UC）样患者（5%）；44例患者（71%）被诊断为其他无法分类的IBD。患者经常需要肠外营养（40%）、广泛免疫抑制（31%）、造血干细胞移植（29%）和腹部手术（19%）。在31%的患者中，确定了潜在的单基因疾病（EPCAM、IL10、IL10RA、IL10RB、FOXP3、LRBA、SKIV2L、TTC37、TTC7A）。单基因IBD中明显更常见的表型特征为：近亲结婚、出生后6个月内发病、发育迟缓、广泛肠道疾病以及上皮异常的组织学证据。
2岁前发病的儿童IBD通常无法分类为克罗恩病和溃疡性结肠炎，尤其是对治疗有抵抗性，并且可能与具有IBD样表型的单基因疾病难以区分。
