Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis.
OBJECTIVE
An attenuated form of familial adenomatous polyposis has been described, but the phenotype remains poorly understood.


METHODS
We performed genetic testing on 810 individuals from 2 attenuated familial adenomatous polyposis kindreds harboring an identical germline adenomatous polyposis coli gene mutation. Colonoscopy was performed on mutation-positive persons.


RESULTS
The disease-causing mutation was present in 184 individuals. Adenomatous polyps were present in 111 of 120 gene carriers who had colonoscopy at an average age of 41 years. The median number of adenomas was 25 (range, 0-470), with striking variability of polyp numbers and a proximal colonic predominance of polyps. Colorectal cancer occurred in 27 mutation carriers (average age, 58 years; range, 29-81 years), with 75% in the proximal colon. The cumulative risk of colorectal cancer by age 80 was estimated to be 69%. An average of 3.4 recurrent polyps (range, 0-29) were found in the postcolectomy rectal remnant over a mean of 7.8 years (range, 1-34 years), with 1 rectal cancer.


CONCLUSIONS
This investigation shows that attenuated familial adenomatous polyposis in the kindreds examined shows a much smaller median number of polyps than typical familial adenomatous polyposis, a wide variability in polyp number even at older ages, and a more proximal colonic location of polyps and cancer, yet it is associated with an extremely high risk of colon cancer. The phenotype of attenuated familial adenomatous polyposis mimics typical familial adenomatous polyposis in some cases but in others is difficult to distinguish from sporadic adenomas and colorectal cancer, thus making genetic testing particularly important.
Burt
Randall W
RW
Department of Medicine, University of Utah, Salt Lake City, USA. randall.burt@hci.utah.edu
Leppert
Mark F
MF
Slattery
Martha L
ML
Samowitz
Wade S
WS
Spirio
Lisa N
LN
Kerber
Richard A
RA
Kuwada
Scott K
SK
Neklason
Deborah W
DW
Disario
James A
JA
Lyon
Elaine
E
Hughes
J Preston
JP
Chey
William Y
WY
White
Raymond L
RL
D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D000293:Adolescent; D000328:Adult; D000368:Aged; D003082:Colectomy; D016145:Endoscopy, Digestive System; D005192:Family Health; D005500:Follow-Up Studies; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D010808:Physical Examination; D012007:Rectum / Q000473:pathology / Q000601:surgery; D012307:Risk Factors; D016019:Survival Analysis