WBR0095

Author	[[PageAuthor::William J Gibson (reviewed by Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Gastrointestinal
Prompt	[[Prompt::A 16-year-old girl presents to her primary care physician complaining of fatigue, gastrointestinal pain, and bloody stools. She denies changes in her diet, nor association of pain with her menstrual cycles. Flexible sigmoidoscopy reveals thousands of polyps lining her colon. Her father was diagnosed with a similar condition at the age of 20 and died shortly thereafter. Her gastrointestinal physician advices her that if she does not undergo colonic resection, she will also die. This condition is most likely caused by a defect in which of the following genes?]]
Answer A	AnswerA::APC gene
Answer A Explanation	[[AnswerAExp::Thousands of colonic polyps in a young patient strongly suggests a diagnosis of familial adenomatous polyposis (FAP). FAP is caused by mutations in the APC gene.]]
Answer B	AnswerB::STK11 gene
Answer B Explanation	[[AnswerBExp::STK11 mutations cause Peutz-Jeghers syndrome. Peutz–Jeghers syndrome, also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa.]]
Answer C	AnswerC::Rb gene
Answer C Explanation	[[AnswerCExp::Rb gene mutations cause familial retinoblastoma, a syndrome characterized by the development of tumors in the eyes of affected infants.]]
Answer D	AnswerD::Wnt gene
Answer D Explanation	[[AnswerDExp::Wnt binding to extracellular receptors can induce beta-catenin signaling, which can cause uncontrolled cell growth. However, activation of beta-catenin signaling is achieved in familial adenomatous polyposis via mutations in the APC gene.]]
Answer E	AnswerE::Beta catenin gene
Answer E Explanation	[[AnswerEExp::Beta catenin becomes dysregulated in familial adenomatous polyposis due to loss of function mutations in APC. APC is a negative regulator of beta-catenin.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::The patient in this vignette is suffering from familial adenomatous polyposis (FAP) syndrome. FAP is an inherited condition in which numerous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when left untreated. This condition most commonly results from mutations in the APC gene, and is inherited in an autosomal dominant pattern. Thus, one copy of the altered gene is sufficient to cause the disorder. APC normally functions to inhibit activity of the beta-catenin transcription factor. In the majority of sporadic cases of colon cancer, either APC or beta-catenin is mutated as well. The incidence of malignancy in cases of FAP approaches 100%. Most individuals with the APC mutation will develop colon cancer by the age of 40. Therefore, prophylactic surgery is generally recommended before the age of 25. There are several surgical options that involve the removal of either the colon or both the colon and rectum. Educational Objective: Familial adenomatous polyposis is caused by loss of function mutations in the APC gene. References: First Aid 2014 page 87, 359; First Aid 2012 page 90,359]]
Approved	Approved::Yes
Keyword	WBRKeyword::Colon, WBRKeyword::Colon cancer, WBRKeyword::Colonoscopy, WBRKeyword::Familial adenomatous polyposis, WBRKeyword::Tumor suppressor, WBRKeyword::Cancer, WBRKeyword::Colorectal cancer, WBRKeyword::Genetics
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