Familial Adenomatous Polyposis (FAP) Mutation Screen

CPT CODE:

  • "DNA Sequence Analysis"
  • 83891/Isolation or extraction of highly purified nucleic acid
  • 83892/x4 Enzymatic digestion
  • 83894/x4 Separation by gel electrophoresis
  • 83898/Amplification, target, each nucleic acid sequence

    USEFUL FOR:

    Confirmation of FAP diagnosis for patients with clinical features  
    This test should be ordered only for individuals with symptoms suggestive of FAP. Asymptomatic patients with a family historyof FAP should not be tested until a mutation has been identifiedin an affected family member.

    SPECIMEN REQUIRED:

    "Molecular Genetics - Inherited Cancer SyndromesPatient Information Sheet" (Supply T519 or see SpecialInstructions) is required for all orders. If not orderingelectronically, please submit the above information sheet alongwith a "Molecular Genetics Request Form" (Supply T245) withthespecimen. An "Informed Consent for DNA Testing"(Supply T576) is available. See Special Instructions for a copyof the form.
    Specimen must arrive within 96 hours of draw.  Draw blood in a lavender-top (EDTA) tube or a yellow-top(ACD) tube, and send 3 mL of EDTA or ACD whole blood inoriginal VACUTAINER. Invert several times to mix blood. Forward unprocessed whole blood promptly at ambienttemperature.

    TRANSPORT TEMPERATURE:

    Ambient\Refrig OK\Frozen NO

    CLINICAL INFORMATION:

    Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by mutations in the APC gene located on the long arm of chromosome 5 (5q21). The incidence of FAP may demonstrate ethnicvariability, however most reports estimate a panethnic incidence somewhere between 1 in 6,000 to 1 in 18,000 individuals. Approximately 25% (1 in 4) of affected individuals are the de novo case in their family.Therefore, FAP is inherited from an affected parent approximately 75%of the time.
    Classic FAP is clinically characterized by the progressive developmentof hundreds to thousands of adenomatous colon polyps, some of whichinevitably progress to carcinoma if the colon is not surgically removed. Polyps may develop during the first decade of life and the majority ofuntreated FAP patients will develop colon cancer by age 40. Typically,there is a predominance of polyps on the left side of the colon, however other areas of the colon my also be affected. The presence of extracolonic manifestations is variable and includes gastric and duodenal polyps, ampullary polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoids tumors, thyroid cancer,hepatoblastoma (most commonly diagnosed before the age of 4 years),and rarely jejunal, adrenal, pancreatic, and biliary tract malignancies.Common constellations of colonic and extracolonic manifestations have resulted in the designation of 3 clinical variants: Gardner syndrome, Turcot syndrome, and hereditary desmoid disease.
    In addition to the typical colonic manifestations of classic FAP, Gardnersyndrome is characterized by the presence of soft tissue tumors (thyroid),osteomas (typically of mandible, but not always), tooth abnormalities(supernumerary) and skin tumors (epidermoid cysts, lipomas, fibromas, leiomyomas).
    Individuals with Turcot syndrome show central nervous system (CNS) tumors in addition to adenomatous polyps. Turcot syndrome is an unusual clinical variant of FAP, as it is also considered a clinical variantof hereditary nonpolyposis colorectal cancer (HNPCC). The types of CNS tumor observed helps to distinguish Turcot-FAP variant patients from Turcot-HNPCC variant patients. The predominant CNS tumor associated with the Turcot -FAP variant is medulloblastoma, whileglioblastoma is the predominant CNS tumor associated with Turcot-HNPCC.
    Hereditary desmoid disease (HDD) is a variant of FAP where multiple desmoids tumors is the predominant feature. Many patients with HDD maynot

    CLINICAL INTERPRETATION:

    An interpretive report will include specimen information, pedigree(when appropriate), assay information, and whether or not resultsare consistent with a diagnosis of FAP, or indicate a risk todevelop FAP.

    REFERENCE VALUES:

    An interpretive report will be provided.