scholarly journals Appropriate Management of Attenuated Familial Adenomatous Polyposis: Report of a Case and Review of the Literature

2019 ◽  
Vol 37 (5) ◽  
pp. 400-405 ◽  
Author(s):  
Aleksandra Sokic-Milutinovic
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Apc Gene ◽  
Colorectal Carcinogenesis ◽  
Endoscopic Polypectomy ◽  
Fundic Gland ◽  
Adenomatous Polyposis ◽  
Attenuated Familial Adenomatous Polyposis ◽  
Increased Risk ◽  
Asymptomatic Individuals ◽  
Immediate Surgery

Hereditary polyposis syndromes in which APC gene germline mutations can lead to colorectal carcinogenesis are familial adenomatous polyposis (FAP), attenuated FAP (AFAP) and MUTYH-associated polyposis. All 3 syndromes increase the potential for the development of colorectal cancer. AFAP is diagnosed if less than 100 adenomas are detected in the colon at presentation. AFAP is inherited in an autosomal dominant manner. We present a case of a 22-year-old female with AFAP who was treated with endoscopic polypectomy and surveilled by annual colonoscopy. Guidelines for AFAP surveillance suggest annual colonoscopy with endoscopic polypectomy in asymptomatic individuals. Indications for immediate surgery include documented or suspected cancer or significant symptoms. Preferred surgical option in AFAP is colectomy and ileo-rectal anastomosis. Surveillance of the AFAP patients should include upper GI endoscopy and duodenoscopy with random biopsies of fundic gland polyps and endoscopic resection of detected adenomas. Annual thyroid ultrasound is indicated due to increased risk for thyroid cancer. In pediatric patients tested positive for germline mutation of APC gene screening for hepatoblastoma using alpha-fetoprotein and liver ultrasound should be performed.

Multiple Approach to the Exploration of Genotype-Phenotype Correlations in Familial Adenomatous Polyposis

2003 ◽  
Vol 21 (9) ◽  
pp. 1698-1707 ◽  
Author(s):  
L. Bertario ◽  
A. Russo ◽  
P. Sala ◽  
L. Varesco ◽  
M. Giarola ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Multiple Correspondence Analysis ◽  
Retinal Pigment ◽  
Clinical Manifestations ◽  
Apc Gene ◽  
Adenomatous Polyposis ◽  
Mutation Site ◽  
Cancer Predisposition Syndrome ◽  
Increased Risk

Purpose: Familial adenomatous polyposis (FAP), caused by a mutation in the APC gene, is a colorectal cancer predisposition syndrome associated with several other clinical conditions. The severity of the FAP is related to the position of the inherited mutation in the APC gene. We analyzed a large series of FAP patients to identify associations among major clinical manifestations and to correlate the mutation site with specific disease manifestations. Materials and Methods: APC mutations were identified in 953 FAP patients from 187 families. We used unconditional logistic regression models and a method involving generalized estimating equations to investigate the association between genotype and phenotype. We used multiple correspondence analysis to represent the interrelationships of a multiway contingency table of the considered variables. Results: APC germline mutations were located between codons 156 and 2011 of the APC gene. Mutations spanning the region between codons 543 and 1309 were variable, but strongly associated with congenital hypertrophy of retinal pigment epithelium. Mutations between codons 1310 and 2011 were associated with a six-fold risk of desmoid tumors relative to the low-risk reference region (159 to 495). Mutations at codon 1309 were associated with early development of colorectal cancer. Mutations between codons 976 and 1067 were associated with a three- to four-fold increased risk of duodenal adenomas. The cumulative frequency of extracolonic manifestations was highest for mutations between codons 976 and 1067, followed by mutations between 1310 and 2011. Conclusion: Analysis of the relation between APC mutation site and phenotype identifies subgroups of FAP patients at high risk for major extracolonic disease, which is useful for surveillance and prevention.

scholarly journals Identification of an APC Variant in a Patient with Clinical Attenuated Familial Adenomatous Polyposis

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Andrew T. Schlussel ◽  
Susan S. Donlon ◽  
Faye A. Eggerding ◽  
Ronald A. Gagliano
Keyword(s):  
Case Report ◽  
Familial Adenomatous Polyposis ◽  
Apc Gene ◽  
Adenomatous Polyposis ◽  
Invasive Adenocarcinoma ◽  
Unclassified Variant ◽  
Attenuated Familial Adenomatous Polyposis ◽  
Mutant Variant ◽  
Pathogenic Analysis ◽  
Tumor Dna

Introduction.The objective of this case report is to discuss an unclassified germline variant of the adenomatous polyposis coli (APC) gene identified in an older patient with attenuated familial adenomatous polyposis syndrome (AFAP).Methods.We present a case report of a 66-year-old man diagnosed with AFAP. Colonoscopy found multiple polyps and invasive adenocarcinoma arising in the transverse colon. Samples were tested for mutations in the APC gene.Results.DNA sequencing of germline DNA identified a cytosine (C) to thymine (T) transition at nucleotide 1240, heterozygous. The C to T transition at codon 414 is predicted to convert an arginine residue to a cysteine that is possibly pathogenic. Analysis of the patient’s colon tumor DNA indicated that the tumor had lost the mutant variant allele and retained only the normal allele, suggesting that the variant may not be significant.Conclusions.The p.R414C variant has been described previously as a germline mutation of probable pathogenicity. This substitution should be considered an unclassified variant and possibly not pathogenic. These findings support the need for further genetic testing of tissue, as well as for developing a mechanism for testing all variants, as this could significantly impact the lives of patients and their family members.

Attenuated familial adenomatous polyposis due to a mutation in the 3′ part of the APC gene. A clue for understanding the function of the APC protein

1996 ◽  
Vol 97 (5) ◽  
pp. 579-584 ◽  
Author(s):  
W. Friedl ◽  
Stephanie Meuschel ◽  
Reiner Caspari ◽  
Christof Lamberti ◽  
Stefan Krieger ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Apc Gene ◽  
Adenomatous Polyposis ◽  
Attenuated Familial Adenomatous Polyposis ◽  
Apc Protein

Attenuated Familial Adenomatous Polyposis: A Case Report With Mixed Features and Review of Genotype-Phenotype Correlation

2005 ◽  
Vol 129 (11) ◽  
pp. 1401-1404
Author(s):  
Diana N. Ionescu ◽  
Georgios Papachristou ◽  
Robert E. Schoen ◽  
Madhuri Hedge ◽  
C. Sue Richards ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Phenotypic Expression ◽  
Complete Characterization ◽  
Apc Gene ◽  
Molecular Testing ◽  
Adenomatous Polyposis ◽  
Attenuated Familial Adenomatous Polyposis ◽  
Mixed Features ◽  
Apc Mutation

Abstract Familial adenomatous polyposis represents approximately 1% of all colorectal cancers and is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Most mutations are located within the first 2000 codons, and several mutational hot spots have been identified. The relative location of the mutation may be associated with the number of polyps and partially predicts specific phenotypic expression. Mutations associated with the attenuated phenotype are found predominantly in the 5′ region of the gene or in the last third. We describe a patient with a mutation in codon 161 of the APC gene, which displays a phenotype most closely resembling the attenuated form of familial adenomatous polyposis, and review the literature, the implications of this mutation, and the importance of the molecular testing in the proper and more complete characterization of these patients. Differences in the APC mutation sites alone cannot completely account for intrafamilial and interfamilial variation in the polyposis phenotypes.

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