Division of Gastroenterology, University of California-San Diego School of Medicine, San Diego, California.
Divisions of Gastroenterology and Clinical Cancer Genomics, Center for Precision Medicine, City of Hope National Medical Center, Duarte, California.
Gastrointest Endosc. 2022 Jun;95(6):1025-1047. doi: 10.1016/j.gie.2022.02.044. Epub 2022 Apr 26.
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S. Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
胃肠道错构瘤性息肉综合征是罕见的常染色体显性遗传病，与良性和恶性肠内和肠外肿瘤的风险增加有关。这些综合征包括 Peutz-Jeghers 综合征、青少年息肉病综合征、PTEN 错构瘤肿瘤综合征（包括 Cowden 综合征和 Bannayan-Riley-Ruvalcaba 综合征）和遗传性混合息肉病综合征。诊断基于临床标准，在某些情况下，通过证明种系致病性变异的存在来确认。最被理解的错构瘤性息肉综合征是 Peutz-Jeghers 综合征，由 STK11 基因的种系致病性变异引起。该综合征的治疗重点是预防息肉引起的小肠出血和机械性梗阻，并监测癌症风险增加的器官。青少年息肉病综合征是由 SMAD4 或 BMPR1A 基因的种系致病性变异引起的，其临床过程不同。携带 SMAD4 致病性变异的患者可能会出现大量胃息肉，导致胃肠道出血和/或蛋白丢失性胃炎。携带 SMAD4 突变的患者通常同时发生遗传性出血性毛细血管扩张症（青少年息肉病综合征-遗传性出血性毛细血管扩张症重叠综合征），可导致鼻出血、黏膜毛细血管扩张引起的胃肠道出血和动静脉畸形。PTEN 基因的种系致病性变异导致重叠的临床表型（称为 PTEN 错构瘤肿瘤综合征），包括 Cowden 综合征和相关疾病，这些疾病与胃肠道和结肠息肉、结肠癌以及其他肠外表现和癌症的风险增加有关。由于错构瘤性息肉综合征相对罕见，因此管理建议基于少数研究。美国多学会大肠癌工作组共识声明总结了这些疾病的临床特征，评估了当前的文献，并为这些疾病患者的诊断、评估和管理提供了指导，重点是内镜管理。
