Boland C Richard, Idos Gregory E, Durno Carol, Giardiello Francis M, Anderson Joseph C, Burke Carol A, Dominitz Jason A, Gross Seth, Gupta Samir, Jacobson Brian C, Patel Swati G, Shaukat Aasma, Syngal Sapna, Robertson Douglas J
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.
Gastroenterology. 2022 Jun;162(7):2063-2085. doi: 10.1053/j.gastro.2022.02.021. 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病综合征是罕见的常染色体显性疾病，与肠道及肠道外良性和恶性肿瘤风险增加相关。它们包括黑斑息肉综合征、幼年性息肉病综合征、PTEN错构瘤肿瘤综合征（包括考登综合征和班纳扬-莱利-鲁瓦尔卡巴综合征）以及遗传性混合性息肉病综合征。诊断基于临床标准，在某些情况下，通过证明存在种系致病性变异来确诊。最广为人知的错构瘤性息肉病综合征是黑斑息肉综合征，由STK11基因的种系致病性变异引起。管理重点在于预防息肉导致的小肠出血和机械性梗阻，以及对癌症风险增加的器官进行监测。幼年性息肉病综合征由SMAD4或BMPR1A基因的种系致病性变异引起，临床病程各异。携带SMAD4致病性变异的患者可能有大量胃息肉，可导致胃肠道出血和/或蛋白丢失性胃病。携带SMAD4突变的患者通常同时患有遗传性出血性毛细血管扩张症（幼年性息肉病综合征-遗传性出血性毛细血管扩张症重叠综合征），可导致鼻出血、黏膜皮肤毛细血管扩张引起的胃肠道出血以及动静脉畸形。PTEN基因的种系致病性变异会导致重叠的临床表型（称为PTEN错构瘤肿瘤综合征），包括考登综合征及相关疾病，这些疾病与胃肠道和结肠息肉病、结肠癌以及其他肠道外表现和癌症的风险增加相关。由于错构瘤性息肉病综合征相对罕见，管理建议基于的研究较少。本美国结直肠癌多学会特别工作组的共识声明总结了临床特征，评估了当前文献，并为错构瘤性息肉病综合征患者的诊断、评估和管理提供指导，重点是内镜管理。
