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GENATLAS PHENOTYPE
last update : 30/08/2006
Symbol FAP
Location 5q22.2
Name familial adenomatous polyposis
Other name(s)
  • hereditary colon cancer syndrome
  • included: Gardner syndrome and Turcot syndrome (FAP + medulloblastoma)(MIM 276300)
    • Corresponding gene APC
    Other symbol(s) ACR, AFAP, FPC, CRC, DEL5Q
    Main clinical features
  • hundreds to thousands of adenomatous colorectal polyps occur during the second and third decades, progressing in cancer in nearly 100 percent of untreated patients
  • frequent extracolonic manifestations such as upper gastrointestinal tract tumours, osteomas, epidermoid cysts and desmoid tumors, congenital hypertrophy of retinal pigment epithelium
  • desmoid tumors are thought to develop in about 10-25 percent of FAP patients and may be the leading cause of death among those who have undergone colectomy.
    • Genetic determination autosomal dominant
    Prevalence 1 in 13,000 births; nearly 1 percent of colorectal cancer cases are due to FAP
    Related entries CHRPE
    Function/system disorder digestive tract/gastrointestinal
    neoplasia
    Type malignancy
    Gene product
    Name negative regulator of beta-catenin (APC)
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types   haploinsufficiency mostly intragenic truncating mutations
      deletion haploinsufficiency large deletions of the APC region with a frequency of >10p.cent amongst non-mutated patients, variable size, de novo or dominantly inherited
    deletion     partial and whole gene deletions
    Remark(s) the position of the germline mutation (first hit) was shown to be a major determinant of the somatic mutation (second hit)
    Genotype/Phenotype correlations
  • while most total and partial APC deletions lead to a classic FAP phenotype, specific (in-frame) deletions may lead to an attenuated polyposis phenotype.
  • phenotypic variations are not entirely explained by the site of the germline mutation and are suggestive of FAP modifier genes
  • congenital hypertrophy of retinal pigment epithelium with mutations codons 463-1387, desmoid tumors (mutations codons 1444-1598 and 1924) and other extracolonic manifestation
  • visible deletions of the APC region are frequently associated with mental retardation and dysmorphic features