Familial Adenomatous Polyposis Clinical Presentation
- Author: Mohammad Wehbi, MD; Chief Editor: BS Anand, MD more...
Most patients with FAP are asymptomatic until they develop cancer. As a result, diagnosing presymptomatic patients is essential.
Of patients with FAP, 75-80% have a family history of polyps and/or colorectal cancer at age 40 years or younger.
Nonspecific symptoms, such as unexplained rectal bleeding (hematochezia), diarrhea, or abdominal pain, in young patients may be suggestive of FAP.
One study suggested a potential association between FAP and type 2 diabetes, but further studies are needed to confirm this association.
Congenital hypertrophy of the retinal pigment epithelium is highly specific for FAP and is best seen by slit-lamp examination. These are discrete flat pigmented lesions of the retina. These are often multiple (63%) and bilateral (87%). They do not cause any clinical problems.
They indicate that a family member has inherited the gene that causes FAP and is at risk. As a result, they precede polyposis and correlate with mutations between exons 9 and 15 of the gene that causes FAP.
Some lesions are indicative of a Gardner variant of FAP, including the following:
Osteomas (painless bony overgrowth) of the skull and the mandible may be present. They usually precede the clinical or radiologic diagnosis of intestinal polyposis.
Dental abnormalities, often diagnosed by using x-ray films, may include supernumerary teeth, impacted teeth, dentigerous cysts, and odontomas.
In prepubescent patients, epidermoid cysts on the legs, face, scalp, and arms may be present. They are the most common cutaneous manifestation of Gardner syndrome. These cysts are benign and mainly pose a cosmetic concern.
Fibromas may be present, located on the scalp, shoulders, arms, and back.
Desmoid tumors are discussed in Mortality/Morbidity.
Juvenile nasopharyngeal angiofibromas (JNA) are a rare, invasive, destructive tumor of the nasopharynx that can be sporadic or associated with FAP.
Fundic gland polyps (FGP) are found in most patients, half of whom will also have dysplastic polyps. Dysplasia is associated with increased severity of antral gastritis and duodenal polyposis. Acid-suppressive therapy appears to be protective against dysplasia. Helicobacter pylori association is rare.
A palpable abdominal mass in a young patient is suggestive of FAP.
A palpable mass upon rectal examination in a young patient is suggestive of FAP.
FAP is caused by a germline mutation of the APC tumor suppressor gene, located on band 5q21. Most mutations of the APC gene are nonsense or frameshift mutations, leading to truncation of the APC protein (nonfunctional protein).
More virulent forms of FAP are associated with a mutation in exon 15 between codons 1250 and 1464, the middle portion of the gene.
In patients with AAPC, mutations of the APC gene occur at the extreme amino terminus of the protein.
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