Liu Haoying, Shen Yinxian, Xu Jiaxin, Huang Shangzhan, Qin TingTing, Zhou Qi, Liao Jiazhi, Xiao Fang
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Biliary-Pancreatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
BMC Gastroenterol. 2025 Jun 5;25(1):432. doi: 10.1186/s12876-025-04041-4.
Monogenic inflammatory bowel disease (mIBD) in patients with onset after the age of 16 has been increasingly recognized, but these reports are sporadic and lack a systematic overview, leaving the clinical and genetic characteristics poorly understood. This study aimed to characterize these late-onset mIBD (LO-mIBD), using an infantile-onset population as a control.
Data were extracted from eligible case reports, case series, and cohorts published between January 1990 and October 2023. A comprehensive search of PubMed and Web of Science was conducted following PRISMA guidelines. Demographic, genetic, phenotypic, and genotypic data were collected for the comparative analysis between LO-mIBD (> 16 years) and infantile-onset mIBD (IO-mIBD, < 2 years) cases that met the inclusion criteria.
A total of 436 IO-mIBD and 110 LO-mIBD cases were included in the analysis. Patients with LO-mIBD had significantly lower rates of parental consanguinity and a higher frequency of heterozygous mutations in autosomal dominant genes compared with IO-mIBD cases. Meanwhile, patients with LO-mIBD more commonly presented with Crohn's disease (CD)-like gastrointestinal phenotypes. They exhibited markedly higher rates of intestinal ulcers, strictures, small intestinal involvement, and granulomatous pathology but fewer instances of villous atrophy, perianal disease, oral lesions, recurrent infections, and fever compared with IO-mIBD cases. The genes most commonly implicated in LO-mIBD were SLCO2A1, GUCY2C, CTLA4, CYBB, and SLC26A3. Defects affecting intestinal epithelial function and phagocytic activity were more prominent in LO-mIBD than in IO-mIBD.
Patients with LO-mIBD exhibited diverse intestinal phenotypes dominated by CD-like disease, with gene defects predominantly involving epithelial and phagocytic functions. Genetic counseling, genotype-phenotype mapping, and functional validation of key pathways are critical for further improving the clinical management of patients with LO-mIBD.
16岁后发病的单基因炎症性肠病（mIBD）已得到越来越多的认识，但这些报道较为零散，缺乏系统概述，导致其临床和遗传特征尚不清楚。本研究旨在以婴幼儿期发病的人群作为对照，对这些晚发型mIBD（LO-mIBD）进行特征描述。
数据从1990年1月至2023年10月发表的符合条件的病例报告、病例系列和队列研究中提取。按照PRISMA指南对PubMed和Web of Science进行全面检索。收集符合纳入标准的LO-mIBD（>16岁）和婴幼儿期发病的mIBD（IO-mIBD，<2岁）病例的人口统计学、遗传、表型和基因型数据，进行对比分析。
分析共纳入436例IO-mIBD和110例LO-mIBD病例。与IO-mIBD病例相比，LO-mIBD患者的父母近亲结婚率显著较低，常染色体显性基因杂合突变频率较高。同时，LO-mIBD患者更常表现出克罗恩病（CD）样胃肠道表型。与IO-mIBD病例相比，他们的肠道溃疡、狭窄、小肠受累和肉芽肿性病理发生率明显更高，但绒毛萎缩、肛周疾病、口腔病变、反复感染和发热的情况较少。LO-mIBD中最常涉及的基因是SLCO2A1、GUCY2C、CTLA4、CYBB和SLC26A3。影响肠道上皮功能和吞噬活性的缺陷在LO-mIBD中比在IO-mIBD中更突出。
LO-mIBD患者表现出以CD样疾病为主的多种肠道表型，基因缺陷主要涉及上皮和吞噬功能。遗传咨询、基因型-表型映射以及关键通路的功能验证对于进一步改善LO-mIBD患者的临床管理至关重要。
