Cancer prone diseases
Educational items 🇬🇧 🇪🇸 🇫🇷 🇩🇪 🇮🇹 🇨🇳
To the top
Other actions (beta)
Download as PDF
Familial adenomatous polyposis (FAP)
INSERM U434, Fondation Jean Dausset - C.E.P.H., 27, rue Juliette Dodu, 75010 Paris, France
Familial adenomatous polyposis (FAP)
Adenomatous polyposis of the colon , Gardner syndrome
autosomal dominant disorder; frequency is about 2.5\/10
5 newborns; neomutation in 20%; variable expressivity; penetrance close to 100% by the age of 40 yrs.
733 Familial adenomatous polyposis
Phenotype and clinics
multiple adenomatous polyps of the colon and the rectum
polyps also develop in the upper gastrointestinal tract
other: pigmented retinal lesions (congenital hypertrophy of the retinal pigment epithelium), jaw cysts, sebaceous cysts, desmoid tumours, and osteomas.
- colorectal cancer(s) develop from the polyps through a dysplastic stage
- malignancies may be found in other sites: liver (hepatoblastoma), brain (medulloblastoma), thyroid.
colorectal cancer in early adult life (median age: 40 yrs) is the first cause of death in this disease.
Genes involved and Proteins
tumour suppressor gene; the APC normal gene product interacts with the adherens junction proteins a and β-catenin
FAP is caused by a highly heterogeneous spectrum of point mutations that represents a problem for molecular genetic diagnosis; but all the mutations are chain terminating and some correlations between the position of the mutation and the phenotypic consequences have been described:
- germline mutations between codons 1250 and 1464 are associated with profuse polyposis;
- an attenuated adenomatous polyposis coli (AAPC) is associated with mutations located very close to the 5-prime end of the APC gene;
- the extent of congenital hypertrophy of the retinal pigment epithelium (CHRPE) depends on the position of the protein-truncating mutation in APC; CHRPE lesions are almost always absent if the mutation occur before exon 9, but are consistently present if it occurs after this exon;
- patients with a mutation between codons 1445 and 1578 do not express CHRPE; however, these patients developed severe desmoid tumors.
To be noted
http:\/\/www.geneclinics.org\/profiles\/fap Familial Adenomatous Polyposis - GeneClinics
Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.
Adam R et al
Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis: rationale and update.
Aihara H et al
Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?
Aretz S et al
Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis.
Attard TM et al
Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis.
Burt RW et al
Duodenal adenoma surveillance in patients with familial adenomatous polyposis.
Campos FG et al
Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report with review of the literature.
Cao Y et al
FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer.
Cetta F et al
The ABC of APC.
Fearnhead NS et al
Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation.
Giardiello FM et al
Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas.
Grover S et al
NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019.
Gupta S et al
ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis).
Hegde M et al
Impact of screening examinations on survival in familial adenomatous polyposis.
Heiskanen I et al
Prevalence of thyroid cancer in familial adenomatous polyposis syndrome and the role of screening ultrasound examinations.
Herraiz M et al
Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1.
Jaeger E et al
Screening for thyroid cancer in patients with familial adenomatous polyposis.
Jarrar AM et al
Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin.
Jasperson KW et al
Clinical significance of the house dust mite (Dermatophagoides pteronyssinus) in asthmatic children in Japan.
Kabasawa Y et al
Defining phenotypes and cancer risk in hyperplastic polyposis syndrome.
Kalady MF et al
Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome.
Koornstra JJ et al
Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.
Li J et al
The genetics of FAP and FAP-like syndromes.
Lipton L et al
Familial adenomatous polyposis.
Macrae F et al
American founder mutation for attenuated familial adenomatous polyposis.
Neklason DW et al
Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.
Nieuwenhuis MH et al
Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.
Palles C et al
The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature.
Repak R et al
The adenomatous polyposis coli (APC) tumour suppressor--genetics, function and disease.
Sieber OM et al
Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis.
Sinha A et al
Upper gastrointestinal cancer in patients with familial adenomatous polyposis.
Spigelman AD et al
The prevalence of thyroid cancer and benign thyroid disease in patients with familial adenomatous polyposis may be higher than previously recognized.
Steinhagen E et al
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S et al
Guidelines for the clinical management of familial adenomatous polyposis (FAP).
Vasen HF et al
A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.
Weren RD et al
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome.
Worthley DL et al
Phenotype associated with recessively inherited mutations in DNA mismatch repair (MMR) genes.
de Vos M et al
Surgical management for advanced duodenal adenomatosis and duodenal cancer in Dutch patients with familial adenomatous polyposis: a nationwide retrospective cohort study.
van Heumen BW et al
Please, confirm that you want to generate a PDF file of this page.
This may take some seconds once process has started. Then it will be opened automatically.
Wait a moment, we are generating the document...