TY - JOUR
T1 - Attenuated familial adenomatous polyposis (AFAP) a phenotypically and genotypically distinctive variant of FAP
AU - Lynch, Henry T.
AU - Smyrk, Thomas
AU - McGinn, Thomas
AU - Lanspa, Stephen
AU - Cavalieri, Jennifer
AU - Lynch, Jane
AU - Slominski‐Castor, Susan
AU - Cayouette, Matthew C.
AU - Priluck, Ira
AU - Luce, Michael C.
PY - 1995/12/15
Y1 - 1995/12/15
N2 - Background. The usual manifestation of familial adenomatous polyposis (FAP) is hundreds or thousands of colonic adenomas. The authors previously described a colon cancer‐prone syndrome characterized by fewer adenomas (1–100), most located in the proximal colon, and upper gastrointestinal lesions, particularly fundic gland polyps and duodenal adenomas. The colonic adenomas are often flat rather than polypoid, a feature emphasized in earlier reports with the term “hereditary flat adenoma syndrome.” The syndrome has an autosomal dominant pattern of inheritance and is linked to the adenomatous polyposis coli [APC] locus at 5q. Methods. This is a descriptive study based on one family that was followed for more than a decade. Total cell RNA was isolated from cultured lymphoblasts, and an in vitro protein synthesis assay was used to detect APC mutations. Sixteen individuals whose APC mutation status was known had sequential endoscopic evaluations. Five patients were given one or more courses of sulindac. Results. There was perfect concordance between clinical affected status and an APC mutation. All affected members generated a 16‐kDa polypeptide from the mutant allele, consistent with a 2‐base pair deletion at the extreme 5′end of the APC gene. Sixteen mutation‐positive individuals underwent upper gastrointestinal endoscopy and colonoscopy; 13 had colonic adenomas, with the number visualized at any one examination ranging from 1 to greater than 50. Upper gastrointestinal examination revealed fundic gland polyps in 15, gastric or duodenal adenomas in 4, and periampullary carcinoma in 1. Conclusion. AFAP is a phenotypically distinctive syndrome, differing from classic FAP by having fewer colonic adenomas that tend to be proximally distributed and flat rather than polypoid. The position of the APC germline mutation appears to allow for the molecular differentiation between FAP and the attenuated variant in that the extreme 5′ APC mutations are associated with the latter.
AB - Background. The usual manifestation of familial adenomatous polyposis (FAP) is hundreds or thousands of colonic adenomas. The authors previously described a colon cancer‐prone syndrome characterized by fewer adenomas (1–100), most located in the proximal colon, and upper gastrointestinal lesions, particularly fundic gland polyps and duodenal adenomas. The colonic adenomas are often flat rather than polypoid, a feature emphasized in earlier reports with the term “hereditary flat adenoma syndrome.” The syndrome has an autosomal dominant pattern of inheritance and is linked to the adenomatous polyposis coli [APC] locus at 5q. Methods. This is a descriptive study based on one family that was followed for more than a decade. Total cell RNA was isolated from cultured lymphoblasts, and an in vitro protein synthesis assay was used to detect APC mutations. Sixteen individuals whose APC mutation status was known had sequential endoscopic evaluations. Five patients were given one or more courses of sulindac. Results. There was perfect concordance between clinical affected status and an APC mutation. All affected members generated a 16‐kDa polypeptide from the mutant allele, consistent with a 2‐base pair deletion at the extreme 5′end of the APC gene. Sixteen mutation‐positive individuals underwent upper gastrointestinal endoscopy and colonoscopy; 13 had colonic adenomas, with the number visualized at any one examination ranging from 1 to greater than 50. Upper gastrointestinal examination revealed fundic gland polyps in 15, gastric or duodenal adenomas in 4, and periampullary carcinoma in 1. Conclusion. AFAP is a phenotypically distinctive syndrome, differing from classic FAP by having fewer colonic adenomas that tend to be proximally distributed and flat rather than polypoid. The position of the APC germline mutation appears to allow for the molecular differentiation between FAP and the attenuated variant in that the extreme 5′ APC mutations are associated with the latter.
KW - APC gene
KW - colon cancer
KW - genetics
KW - hereditary flat adenoma
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U2 - 10.1002/1097-0142(19951215)76:12<2427::AID-CNCR2820761205>3.0.CO;2-B
DO - 10.1002/1097-0142(19951215)76:12<2427::AID-CNCR2820761205>3.0.CO;2-B
M3 - Article
C2 - 8625067
AN - SCOPUS:0028823186
SN - 0008-543X
VL - 76
SP - 2427
EP - 2433
JO - Cancer
JF - Cancer
IS - 12
ER -