Care of Patients and Their Families With Familial Adenomatous Polyposis

doi:10.4065/75.1.57

Mayo Clinic Proceedings

Volume 75, Issue 1, January 2000, Pages 57-67

https://doi.org/10.4065/75.1.57 Get rights and content

Familial adenomatous polyposis (FAP) is a dominantly inherited disorder that is typically characterized by the appearance of multiple colorectal adenomas usually by the teenage years, with a risk of early colorectal cancer approaching 100%. Genetic testing can help determine which family members have the disorder and require sur-veillance endoscopy. Astute physicians may detect unsuspected FAP in patients with extraintestinal manifestations such as hard or soft cutaneous tumors. Colectomy will prevent cancer but is often necessary before the patient is 20 years old. Postoperative lifelong surveillance is indicated to screen for associated duodenal, thyroid, and rectal or ileal neoplasms. Attenuated FAP variants are less typical and may be confused with other types of familial colorectal neoplasia. Chemoprevention, regression, and other treatment strategies are being developed to improve the management of extracolonic neoplasms and desmoid tumors. A better understanding of the natural history of these FAP-associated AP-associated phenomena will facilitate the rational selection of interventions. Management guidelines that were recently developed at Mayo Clinic Rochester to provide for uniform care and surveillance are discussed.

Section snippets

CLINICAL FEATURES AND NATURAL HISTORY

Typically, FAP is characterized by the formation of multiple (hundreds to thousands) adenomatous polyps in the colorectum, usually beginning at puberty although sometimes earlier.⁸ Symptoms such as bleeding, change in bowel habit, or abdominal pain are often due to many large polyps or frank cancer and are unusual before the patient is 20 years old. Cancer is frequent by the time the patient is 40 years old and is often unresectable in those with symptoms.9, 10, 11 An attenuated phenotype

MOLECULAR GENETICS

Genetic linkage analysis was first used to identify the site of the mutation in FAP in a small region of chromosome 5 (5q21).⁵ Gene carrier testing with use of linkage analysis benefits only some patients with FAP because several family members are needed for the analysis. Direct genetic testing became feasible when the APC gene on chromosome 5q21 was found to be mutated in the germline in FAP. The mutations in FAP are of various types (insertions, deletions, nonsense, etc) but often lead to

Genetic Testing

Genetic counseling should be offered to persons with an increased risk of FAP AP due to family history or the finding of multiple colonic polyps,³⁴ as well as patients in whom the diagnosis of FAP AP was established at endoscopy. Genetic testing can be done after its consequences have been thoroughly discussed. The benefits for persons with a 50% risk of FAP include a reduction in uncertainty, modification in screening guidelines for those without a mutation, and increased compliance for those

Colorectal Neoplasia and Surgical Options

Virtually all untreated patients with FAP develop colorectal cancer at a mean age of 40 years.⁴⁴ Once polyposis has been established, surgery is generally indicated when the patient is 17 to 20 years old or sooner if diffuse polyposis or carpeting is evident. However, timing of colectomy must be tailored to the individual patient.3, 45 Total proctocolectomy with ileal pouch-anal anastomosis including mucosectomy to the dentate line is generally favored at Mayo Clinic Rochester because of

MANAGEMENT GUIDELINES

Guidelines for the management of patients with FAP and at-risk family members were recently developed by a rnultispecialty group at Mayo Clinic Rochester to facilitate uniform care and surveillance. These guidelines represent a consensus from the Division of Gastroenterology and Hepatology and the departments of general and colorectal surgery, genetics, and oncology. Actual practice will vary depending on individual patient requirements. These suggestions provide a plan for rational and uniform

REGISTRIES

After the London (St Mark's Hospital) Registry was established in the early 1900S,³ other registries of families with inherited colorectal cancer were established quickly in Europe and later in the United States.⁴ In addition to the Colorectal Cancer Prevention Registry at the Mayo Clinic in Rochester, Minn, there are more than 135 registries worldwide today. Registries provide a listing of families at high risk for the development of colorectal cancer and a mechanism to contact them for

Chemoprevention

Sulindac and other nonsteroidal anti-inflammatory drugs have been shown to shrink existing rectal adenomas and prevent their recurrence in some FAP patients.⁵² However, these agents have toxic effects and have not shown the same benefits on proximal gut adenomas in patients with FAP. Chemopreventive agents that are currently under investigation may improve prophylactic management of neoplasia in the proximal gut and pouches of patients with FAP. Effective and safe chemoprevention would provide

SUMMARY

Although FAP accounts for only about 1% of approximately 150,000 new cases of colon cancer annually in the United States, it affects young people and, unless detected early, is almost uniformly fatal by the time the patient is 45 years old. Colectomy saves lives, but lifelong surveillance is necessary. Identification of at-risk persons and standardized follow-up are facilitated by a registry with a computerized database that allows for coordination and implementation of research and management

ACKNOWLEDGMENT

Dr Alex Geller provided Fig. 1, Fig. 3, Fig. 5; Dr Helmut Buettner provided Figure 2, and Dr Roger R. Dozois provided Figure 4.

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Hereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance.
A MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed.
The most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance.
Medical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members.
Hereditary polyposis CRC
2021, Foundations of Colorectal Cancer
The term hereditary polyposis syndromes encompasses a series of conditions that involve the development of numerous polyps in the gastrointestinal lumen, and a higher risk of developing colorectal cancer.
Associated extraintestinal manifestations are also frequent.
Traditionally, these syndromes were classified according to the histology of the polyps, but the development of genetic tests has modified their classification, diagnosis, and prevention strategies, enabling us to reduce the risk of developing colorectal cancer.
Genetic Factors: Hereditary Cancer Predisposition Syndromes
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The hereditary burden of human cancer is composed of rare syndromes resulting in high risk for malignancies, often involving multiple organ systems, as well as more common genomic variants associated with a moderate risk for disease. The diagnosis of cancer predisposition syndromes can usually be confirmed with molecular genetic testing of patients based on clinical, pathologic, or family history indicators. Genetic testing can be extended to relatives as a predictive guide to their preventive management. This chapter will review the major syndromes of cancer predisposition, diagnosis, and management. Because tumor genomic analysis often includes a comparison with the inherited DNA sequence, targeted approaches to oncologic therapy also create opportunities for precision prevention in cancer-affected families.
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Citation Excerpt :
Depending on RET mutation risk level, the recommended age for prophylactic thyroidectomy varies from 6 months with the highest risk (MEN2B), to early adulthood with moderate risk [6,16]. The frequency of FAP is estimated between 1 in 5,000 to 1 in 25,000 [48]. Those affected by FAP develop hundreds of colon polyps and early-onset colon cancer.
Endocrine tumor syndromes, eg, multiple endocrine neoplasia types 1 and 2, were among the first recognized hereditary predisposition syndromes to tumor development. Over time, the number of endocrine tumor syndromes has significantly expanded, eg, with the recent inclusion of hereditary paraganglioma syndromes. Associations of non-endocrine tumors with hereditary endocrine tumor syndromes and endocrine tumors with non-classical endocrine tumor syndromes have emerged. These findings have certainly expanded the scope of care, necessitating a multidisciplinary approach by a team of medical professionals and researchers, integrating shared patient decision-making at every step of surveillance, diagnosis, and treatment. In the absence of evidence-based guidelines, multiple aspects of patient care remain individualized, based on a patient’s clinical presentation and family pedigree. This is particularly important when determining a surveillance plan for unaffected or disease-free mutation carriers. In this review, we describe the main endocrine tumor manifestations found in familial cancer syndromes in an organ-based approach, focusing on adrenocortical carcinoma, pheochromocytoma and paraganglioma, neuroendocrine tumors, differentiated thyroid cancer, and medullary thyroid cancer. We highlight the challenges in diagnosis, surveillance, and therapy unique to the patient population with hereditary syndromes. Furthermore, we underscore the importance of evaluating for genetic predisposition to tumor development, provide features that can identify index patients, and discuss the approach to screening surveillance for mutation carriers.
The natural history of familial adenomatous polyposis syndrome: A 24 year review of a single center experience in screening, diagnosis, and outcomes
2014, Journal of Pediatric Surgery
Understanding the natural history of Familial Adenomatous Polyposis (FAP) will guide screening and aid clinical management.
Patients with FAP, age ≤ 20 years presenting between 1987 and 2011, were reviewed for presentation, diagnosis, extraintestinal manifestations, polyp burden, family history, histology, gene mutation, surgical intervention, and outcome.
One hundred sixty-three FAP patients were identified. Diagnosis was made by colonoscopy (69%) or genetic screening (25%) at mean age of 12.5 years. Most children (58%) were asymptomatic and diagnosed via screening due to family history. Rectal bleeding was the most common (37%) symptom prompting evaluation. Colon polyps appeared by mean age of 13.4 years with > 50 polyps at the time of diagnosis in 60%. Cancer was found in 1 colonoscopy biopsy and 5 colectomy specimens. Family history of FAP was known in 85%. 53% had genetic testing, which confirmed APC mutation in 88%. Extraintestinal manifestations included congenital hypertrophy of the retinal pigment epithelium (11.3%), desmoids (10.6%), osteomas (6.7%), epidermal cysts (5.5%), extranumerary teeth (3.7%), papillary thyroid cancer (3.1%), and hepatoblastoma (2.5%). Six patients died secondary to FAP.
Clinical presentation and manifestations in pediatric FAP are variable. We suggest an individualized patient-oriented screening algorithm that allows for earlier screening and appropriate management.
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Subspecialty Clinics: Gastroenterology and HepatologyCare of Patients and Their Families With Familial Adenomatous Polyposis

Section snippets

CLINICAL FEATURES AND NATURAL HISTORY

MOLECULAR GENETICS

Genetic Testing

Colorectal Neoplasia and Surgical Options

MANAGEMENT GUIDELINES

REGISTRIES

Chemoprevention

SUMMARY

ACKNOWLEDGMENT

Gastroenterology

Gastroenterology

Am J Hum Genet

J Pediatr

Ant J Ophthalmol

Gaslrointest Endosc

Gastroenterology

Gastroinlest Endosc

Surgery

Gastrointest Endosc

Surgery

Two cases of disseminated polypus of the rectum

Trans Pathol Soc Land

Disseminated polypi of the large intestine becoming malignant: strictures (malignant adenoma) of the rectum and of the splenic flexure of the colon: secondary growths in the liver

Trans Pathol Soc Lond

Molecular Genetics and Colorectal Neoplasia: A Primer for the Clinician

The gene for familial polyposis coli maps to the long arm of chromosome 5

Science

Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers

Science

A genetic study of multiple polyposis of the colon (with an appendix deriving a method of estimating relative fitness)

Am J Hum Gener

Overview of screening and management of familial adenomatous polyposis

Gut

Causes of death and postsurgical survival in familial adenomatous polyposis: results from the Italian Registry

Semin Surg Oncol

Genetic and familial factors in colorectal cancer

Jpn J Clin Oncol

The use and interpretation of commercial APC gene testing for familial adenomatous polyposis

N Engl Med

Apoptosis and APC in colorectal tumorigenesis

Proc Natl Acad Set USA

Lessons from hereditary colorectal cancer

Cell

Clonality of dysplastic epithelium in colorectal adenomas from familial adenomatous polyposis patients

Cancer Res

Polyposis syndromes

Genotype-phenotype correlations at the adeno matous polyposis coli (APC) gene

Crit Rev Oncog

The molecular basis of Turcof s syndrome

N EnglJ Med

Is screening for thyroid carcinoma indicated in familial adenomatous polyposis?

fnt J Colorectal Dis

Subspecialty Clinics: Gastroenterology and Hepatology
Care of Patients and Their Families With Familial Adenomatous Polyposis