Familial Adenomatous Polyposis (FAP) Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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). Classic FAP is characterized by progressive development of hundreds to thousands of adenomatous colon polyps. Polyps may develop during the first decade of life and the majority of untreated 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, osteomas, dental abnormalities (unerupted teeth), congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoids tumors, hepatoblastoma, and extracolonic cancers. Common constellations of colonic and extracolonic manifestations have resulted in the designation of 3 clinical variants: Gardner syndrome, Turcot syndrome, and hereditary desmoid disease.
Gardner syndrome is characterized by colonic polyps of classic FAP with epidermoid skin cysts and benign osteoid tumors fo the mandible and long bones. Turcot syndrome is characterized by multiple colonic polyps and central nervous system (CNS) tumors.
Turcot syndrome is an unusual clinical variant of FAP, as it is also considered a clinical variant of hereditary nonpolyposis colorectal cancer (HNPCC). Individuals with Turcot syndrome have central nervous system (CNS) tumors in addition to adenomatous polyps. 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, while glioblastoma is the predominant CNS tumor associated with Turcot-HNPCC.
Hereditary desmoid disease (HDD) is a variant of FAP with multiple desmoids tumors as the predominant feature. Many patients with HDD may not even show colonic manifestations of FAP. APC germline testing may assist clinicians in distinguishing a sporadic desmoid tumor, from that associated with FAP.
Attenuated FAP (AFAP) is characterized by later onset of disease and a milder phenotype (typically <100 adenomatous polyps and fewer extracolonic manifestations) than classic FAP. Typically individuals with AFAP develop symptoms of the disease at least 10 to 20 years later than classically affected individuals. Individuals with AFAP often lack a family history of colon cancer and/or multiple adenomatous polyps. Of note, clinical overlap is observed between AFAP and MYH-associated polyposis (MAP), an autosomal recessive polyposis syndrome typically associated with fewer than 100 polyps. Although the clinical phenotype of MAP remains somewhat undefined, extracolonic manifestations, including CHRPE have been described in affected patients. Given the phenotypic overlap of AFAP and MAP, these tests are commonly ordered together or in a reflex fashion.
See Hereditary Colorectal Cancer: Adenomatous Polyposis Syndromes (September 2004 Communique') in publications for additional information.
Predictive testing for familial adenomatous polyposis when a mutation has been identified in an affected family member
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order FAPMS / Familial Adenomatous Polyposis (FAP) Mutation Screen.
Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with familial polyposis.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
In addition to disease-related probes, the MLPA technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. American Society of Clinical Oncology. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility Clin Oncol. 2003;21:2397-406
2. Half E, Bercovich D, Rozen P: Familial adenomatous polyposis. Orphanet J Rare Dis 2009 Oct 12;4:22
3. Croner RS, Brueckl WM, Reingruber B, et al: Age and manifestation related symptoms in familial adenomatous polyposis. BMC Cancer 2005;Mar 2;5:24