Clinical manifestations and diagnosis of familial adenomatous polyposis
- Daniel C Chung, MD
Daniel C Chung, MD
- Associate Professor of Medicine
- Harvard Medical School
- Tomer Adar, MD
Tomer Adar, MD
- Research Fellow, Gastroenterology Division
- Massachusetts General Hospital
- Senior Gastroenterologist, Digestive Diseases Institute
- Senior Physician in Internal Medicine, Shaare-Zedek Medical Center
- Hebrew University, Jerusalem, Israel
Familial adenomatous polyposis (FAP) is characterized by the presence of multiple colorectal adenomatous polyps (typically more than 100). Multiple colorectal polyps may also be seen in individuals with MUTYH-associated polyposis and hamartomatous polyposis syndromes (Peutz-Jeghers, juvenile polyposis syndrome, and Cowden syndrome). Other rare causes include germline mutations in DNA polymerase ε (POLE) and δ (POLD1), and Gremlin 1 homolog (GREM1) .
This topic will review the genetics, clinical manifestations, and diagnosis of FAP. Surveillance strategies for FAP and the clinical features and diagnosis of MUTYH-associated polyposis, and the hamartomatous polyposis syndromes are discussed separately. (See "Familial adenomatous polyposis: Screening and management of patients and families" and "MUTYH-associated polyposis" and "Peutz-Jeghers syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Juvenile polyposis syndrome" and "PTEN hamartoma tumor syndrome, including Cowden syndrome".)
Familial adenomatous polyposis (FAP) occurs in approximately 1/10,000 to 1/30,000 live births, and accounts for less than 1 percent of all colorectal cancers in the United States . It affects both sexes equally and has a worldwide distribution.
Familial adenomatous polyposis (FAP) and its variants are caused by germline mutations in the tumor suppressor gene, adenomatous polyposis coli (APC), located on chromosome 5q21-q22 .
FAP follows an autosomal dominant pattern of inheritance with near complete penetrance of the colonic manifestations but variable penetrance of the extracolonic manifestations of the disease. Up to 25 percent of FAP cases are due to new or de novo APC mutations . Such patients do not have a family history of FAP. (See "Genetics: Glossary of terms" and "Overview of Mendelian inheritance" and "Non-Mendelian inheritance patterns of monogenic diseases", section on 'Penetrance' and 'Clinical manifestations' below.)
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- CLINICAL MANIFESTATIONS
- Colonic manifestations
- - Classic FAP
- - Attenuated FAP
- Extracolonic manifestations
- FAP variants
- - Gardner syndrome
- - Turcot syndrome
- Laboratory features
- DIFFERENTIAL DIAGNOSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS