Abstract：
OBJECTIVE: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS.
METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group.
RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations.
CONCLUSIONS: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.
METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group.
RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations.
CONCLUSIONS: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.
摘要：
目的：40％-60％的青少年息肉病综合征（JPS）患者存在SMAD4或BMPR1A基因中的结构性致病变异（DCV）。这项研究的目的是表征与DCV阴性JPS相比，DCV阳性JPS儿童的临床病程和息肉负担。
方法：人口统计学，临床,遗传,JPS患儿的内镜数据来自ESPHGAN/NASPGHAN息肉病工作组的8个国际中心.
结果：共纳入124例JPS患儿：69例（56%）DCV阴性和55例（44%）DCV阳性（53%SMAD4和47%BMPR1A），中位（四分位距[IQR]）随访4年（2.8-6.4）。与DCV阴性儿童相比，DCV阳性儿童被诊断为年龄较大[12（8-15.7）岁与5(4-7)年,分别,p<0.001],息肉综合征家族史的频率较高(50.9%vs.1.4%,p<0.001)，经历了更高的肠外表现频率(27.3%vs.5.8%,p<0.001)，并接受了更多的胃肠手术(16.4%vs.1.4%,p=0.002)。与DCV阴性组相比，DCV阳性组发生新的结肠息肉的发生率为6.15（95％置信区间3.93-9.63，p<0.001）。每年随访平均12.2例，而新息肉为2例。SMAD4和BMPR1A突变患者的息肉负担没有差异。
结论：这项最大的国际儿科JPS队列研究显示，DCV阳性和DCV阴性儿童表现出不同的临床表型。这些发现表明，可能需要基于突变状态的差异化监测策略。
方法：人口统计学，临床,遗传,JPS患儿的内镜数据来自ESPHGAN/NASPGHAN息肉病工作组的8个国际中心.
结果：共纳入124例JPS患儿：69例（56%）DCV阴性和55例（44%）DCV阳性（53%SMAD4和47%BMPR1A），中位（四分位距[IQR]）随访4年（2.8-6.4）。与DCV阴性儿童相比，DCV阳性儿童被诊断为年龄较大[12（8-15.7）岁与5(4-7)年,分别,p<0.001],息肉综合征家族史的频率较高(50.9%vs.1.4%,p<0.001)，经历了更高的肠外表现频率(27.3%vs.5.8%,p<0.001)，并接受了更多的胃肠手术(16.4%vs.1.4%,p=0.002)。与DCV阴性组相比，DCV阳性组发生新的结肠息肉的发生率为6.15（95％置信区间3.93-9.63，p<0.001）。每年随访平均12.2例，而新息肉为2例。SMAD4和BMPR1A突变患者的息肉负担没有差异。
结论：这项最大的国际儿科JPS队列研究显示，DCV阳性和DCV阴性儿童表现出不同的临床表型。这些发现表明，可能需要基于突变状态的差异化监测策略。
