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Der Internist Feb 2021Gastrointestinal polyposis syndromes are the second most common cause of hereditary colorectal carcinomas after Lynch syndrome (hereditary non-polyposis colon cancer,... (Review)
Review
BACKGROUND
Gastrointestinal polyposis syndromes are the second most common cause of hereditary colorectal carcinomas after Lynch syndrome (hereditary non-polyposis colon cancer, HNPCC). The detection of a causal germline mutation in an affected family member serves for differential diagnosis, assessment of the recurrence risk and predictive testing of healthy individuals at risk.
OBJECTIVES
The present article aims to provide an overview of the differential diagnosis of different gastrointestinal polyposis syndromes based on the endoscopic findings, polyp histology, extraintestinal phenotype and molecular genetic diagnostics.
MATERIALS AND METHODS
The present article is based on a literature search on gastrointestinal polyposis syndromes.
RESULTS
In addition to familial adenomatous polyposis (FAP), there are further subtypes of adenomatous polyposis that can often only be distinguished by the detection of a causative germline mutation and are sometimes associated with different extracolonic manifestations. In hamartomatous polyposis syndromes, the clinical overlaps often cause differential diagnostic problems. Serratated polyposis syndrome is possibly the most frequent polyposis syndrome, although its cause is currently largely unexplained.
CONCLUSIONS
Early detection and correct classification of polyposis is crucial for adequate prevention and therapy. Access to multidisciplinary expert centres is useful for the care of families.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Early Detection of Cancer; Humans; Phenotype; Syndrome
PubMed: 33237439
DOI: 10.1007/s00108-020-00903-z -
Frontline Gastroenterology Oct 2019Hereditary bowel tumours are usually part of a distinct syndrome which require management of both intestinal and extra-intestinal disease. Polyposis syndromes include:... (Review)
Review
Hereditary bowel tumours are usually part of a distinct syndrome which require management of both intestinal and extra-intestinal disease. Polyposis syndromes include: Familial adenomatous polyposis, MUTYH-associated polyposis, Serrated polyposis syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome and PTEN-hamartomatous syndromes. Of all colorectal cancers (CRC), 5%-10% will be due to an underlying hereditary CRC syndrome. Diagnosis and management of polyposis syndromes is constantly evolving as new scientific and technological advancements are made with respect to identifying causative genes and increased sophistication of endoscopic therapy to treat polyps. This, in addition to data yielded from meticulous record-keeping by polyposis registries has helped to guide management in what are otherwise relatively rare conditions. These data help guide clinical management of patients and their 'at-risk' relatives. Diagnosis is both genetic where possible but clinical recognition is key in the absence of an identifiable causative gene. Furthermore, some syndromes can overlap which can additionally complicate diagnosis. The principle goals of polyposis management are first to manage and treat the presenting patient and then to identify 'at-risk' patients, through screening and predictive genetic testing, endoscopic surveillance to allow therapy and guide surgical prophylaxis. Due to the complexity of diagnosis and management, patients and their families should be referred to a genetics centre or a polyposis registry where dedicated management can take place.
PubMed: 31656563
DOI: 10.1136/flgastro-2018-101053 -
Best Practice & Research. Clinical... Aug 2017Polyposis syndromes are encountered in endoscopy practice, and are considered rare entities, accounting for ≤1% of colorectal cancer. Polyposis can occur within... (Review)
Review
Polyposis syndromes are encountered in endoscopy practice, and are considered rare entities, accounting for ≤1% of colorectal cancer. Polyposis can occur within inherited syndromes or as "sporadic" cases of unknown etiology. Their proper characterization is relevant for patient management, and should nowadays drive appropriate genetic tests which have a key role in clinical practice for driving surveillance and colorectal cancer prevention, enlarged to relatives. Polyposis classification is based upon polyp number and histology, familial and personal history. This review will explore the polyposis nosology and their genetic determinants in the emerging scenario of Next Generation Sequencing which allow testing multiples genes in parallel. This capability will likely continue to increase the range of polyposis predisposing genes, contributing to define new clinical entities.
Topics: Adenomatous Polyposis Coli; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Syndrome
PubMed: 28842050
DOI: 10.1016/j.bpg.2017.05.011 -
Best Practice & Research. Clinical... 2022Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is... (Review)
Review
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
Topics: Colorectal Neoplasms; Gastrointestinal Neoplasms; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 35988962
DOI: 10.1016/j.bpg.2022.101799 -
Genes Dec 2022Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast... (Review)
Review
Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast cancer (2% of cases). Colorectal cancer is the most common cancer with a strong genetic predisposition, but it includes dozens of various syndromes. This group includes familial adenomatous polyposis, attenuated familial adenomatous polyposis, -associated polyposis, -associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome, and Muir-Torre syndrome. The common symptom of all these diseases is a very high risk of colorectal cancer, but depending on the condition, their course is different in terms of age and range of cancer occurrence. The rate of cancer development is determined by its conditioning genes, too. Hereditary predispositions to cancer of the intestine are a group of symptoms of heterogeneous diseases, and their proper diagnosis is crucial for the appropriate management of patients and their successful treatment. Mutations of specific genes cause strong colorectal cancer predispositions. Identifying mutations of predisposing genes will support proper diagnosis and application of appropriate screening programs to avoid malignant neoplasm.
Topics: Humans; Genetic Predisposition to Disease; Adenomatous Polyposis Coli; Neoplastic Syndromes, Hereditary; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis
PubMed: 36553592
DOI: 10.3390/genes13122326 -
Journal of Pediatric Genetics Jun 2016Familial adenomatous polyposis (FAP), caused by a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21, is an autosomal dominant disorder... (Review)
Review
Familial adenomatous polyposis (FAP), caused by a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21, is an autosomal dominant disorder characterized by hundreds to thousands of adenomas throughout the gastrointestinal tract. A variety of extraintestinal manifestations, including thyroid, soft tissue, and brain tumors, may also be present. These patients inevitably develop colorectal carcinoma by the fourth decade of life. In this review, the pathology, epidemiology, and genetic features of FAP are discussed.
PubMed: 27617147
DOI: 10.1055/s-0036-1579760 -
Gastrointestinal Endoscopy Clinics of... Jan 2022The goal of this review is to provide an overview of evaluating patients with adenomatous polyposis of the colon, including elements such as generating a differential... (Review)
Review
The goal of this review is to provide an overview of evaluating patients with adenomatous polyposis of the colon, including elements such as generating a differential diagnosis, referral considerations for genetic testing, genetic testing options, and expected outcomes from genetic testing in these individuals. In more recent years, adenomatous colonic polyposis has evolved beyond the more robustly characterized familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) now encompassing more newly described genes and associated syndromes. Technological innovation, from whole-exome sequencing to multigene panel testing, has dramatically increased the amount of genotypic and phenotypic data amassed in adenomatous polyposis cohorts, which has contributed greatly to informing diagnosis and clinical management of affected individuals and their families.
Topics: Adenomatous Polyposis Coli; Colonic Neoplasms; Diagnosis, Differential; Genetic Testing; Humans
PubMed: 34798989
DOI: 10.1016/j.giec.2021.08.003 -
Internal Medicine (Tokyo, Japan) Sep 2023A 36-year-old man was diagnosed with multiple gastric polyps by esophagogastroduodenoscopy. Subsequent colonoscopy identified two tubular adenomas, and computed...
A 36-year-old man was diagnosed with multiple gastric polyps by esophagogastroduodenoscopy. Subsequent colonoscopy identified two tubular adenomas, and computed tomography revealed subcutaneous tumors. Based on these findings, we suspected that gastric polyposis was associated with the APC gene, either attenuated familial adenomatous polyposis (AFAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). A genetic analysis demonstrated that he had a frameshift variant at codon 1928 of APC, suggesting AFAP. In this era of less Helicobacter pylori infection and frequent use of proton pump inhibitors, diagnoses of AFAP and GAPPS should be considered in patients with prominent gastric fundic gland polyposis.
Topics: Male; Humans; Adult; Helicobacter Infections; Helicobacter pylori; Adenomatous Polyposis Coli; Stomach Neoplasms
PubMed: 36725040
DOI: 10.2169/internalmedicine.1101-22 -
Annals of Gastroenterology 2018The majority of colorectal cancer (CRC) cases are sporadic, with hereditary factors contributing to approximately 35% of CRC cases. Less than 5% of CRC is associated... (Review)
Review
The majority of colorectal cancer (CRC) cases are sporadic, with hereditary factors contributing to approximately 35% of CRC cases. Less than 5% of CRC is associated with a known genetic syndrome. Although adenomatous polyposis syndromes, hamartomatous polyposis syndromes, and those previously classified as non-polyposis CRC syndromes are quite rare, it is important for clinicians to know the characteristics of each syndrome and to understand the differences in cancer risks between the different conditions. This information is very important when treatment and surveillance plans are formulated for each individual patient.
PubMed: 29333064
DOI: 10.20524/aog.2017.0218 -
Best Practice & Research. Clinical... 2022Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is... (Review)
Review
Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.
Topics: Colon; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Smad4 Protein
PubMed: 35988968
DOI: 10.1016/j.bpg.2022.101802