Familial adenomatous polyposis (FAP)

1998-06-01   Sylviane Olschwang 

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\/105 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.
  • Neoplastic risk

    - 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


    119682 APC


    http:\/\/www.geneclinics.org\/profiles\/fap Familial Adenomatous Polyposis - GeneClinics


    Pubmed IDLast YearTitleAuthors
    274766532016Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.Adam R et al
    241619622014Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis: rationale and update.Aihara H et al
    163177452006Should 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
    172381842007Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis.Attard TM et al
    153005762004Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis.Burt RW et al
    262659882015Duodenal adenoma surveillance in patients with familial adenomatous polyposis.Campos FG et al
    121350432002Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report with review of the literature.Cao Y et al
    266972622015FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer.Cetta F et al
    112571052001The ABC of APC.Fearnhead NS et al
    81947001994Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation.Giardiello FM et al
    228511152012Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas.Grover S et al
    314876812019NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019.Gupta S et al
    243103082014ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis).Hegde M et al
    111993682000Impact of screening examinations on survival in familial adenomatous polyposis.Heiskanen I et al
    172585122007Prevalence of thyroid cancer in familial adenomatous polyposis syndrome and the role of screening ultrasound examinations.Herraiz M et al
    225615152012Hereditary 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
    211736942011Screening for thyroid cancer in patients with familial adenomatous polyposis.Jarrar AM et al
    210394322011Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin.Jasperson KW et al
    10370591976Clinical significance of the house dust mite (Dermatophagoides pteronyssinus) in asthmatic children in Japan.Kabasawa Y et al
    212286632011Defining phenotypes and cancer risk in hyperplastic polyposis syndrome.Kalady MF et al
    227045772012Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome.Koornstra JJ et al
    270873192016Point 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
    169986672006The genetics of FAP and FAP-like syndromes.Lipton L et al
    194141462009Familial adenomatous polyposis.Macrae F et al
    180634162008American founder mutation for attenuated familial adenomatous polyposis.Neklason DW et al
    210634172011Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.Nieuwenhuis MH et al
    232634902013Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.Palles C et al
    273434142016The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature.Repak R et al
    110999512000The adenomatous polyposis coli (APC) tumour suppressor--genetics, function and disease.Sieber OM et al
    205288952011Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis.Sinha A et al
    25710191989Upper gastrointestinal cancer in patients with familial adenomatous polyposis.Spigelman AD et al
    224250612012The prevalence of thyroid cancer and benign thyroid disease in patients with familial adenomatous polyposis may be higher than previously recognized.Steinhagen E et al
    256455742015ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.Syngal S et al
    181949842008Guidelines for the clinical management of familial adenomatous polyposis (FAP).Vasen HF et al
    259389442015A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.Weren RD et al
    218134762012Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome.Worthley DL et al
    160425832005Phenotype associated with recessively inherited mutations in DNA mismatch repair (MMR) genes.de Vos M et al
    222653912012Surgical 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