WBR0095
Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D. and Rim Halaby, M.D. [1])]] |
---|---|
Exam Type | ExamType::USMLE Step 1 |
Main Category | MainCategory::Genetics |
Sub Category | SubCategory::Gastrointestinal |
Prompt | [[Prompt::A 17-year-old girl presents to her primary care physician complaining of fatigue, gastrointestinal pain, and bloody stools. Her menstrual cycle is regular with no menorrhagia or dysmenorrhea. She denies an association of her pain with her menstrual cycles or with food intake. Further questioning reveals that she has a strong family history of colon cancer at young age. Flexible sigmoidoscopy reveals thousands of polyps lining her colon. The patient is referred for genetic studies. A defect in which of the following genes is most likely responsible for the patient's condition?]] |
Answer A | AnswerA::''APC'' gene |
Answer A Explanation | [[AnswerAExp::Tens to thousands of colonic polyps in a young adolescent patient with a positive family history of colon cancer or colectomy at young age 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 protein 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 protein becomes dysregulated in familial adenomatous polyposis due to loss-of-function mutations of APC gene. APC protein is a negative regulator of beta-catenin protein.]] |
Right Answer | RightAnswer::A |
Explanation | [[Explanation::Familial adenomatous polyposis (FAP) syndrome is a genetic disorder in which tens to thousands of polyps form mainly in the epithelium of the rectum and colon during the second decade of life. While these polyps start out benign, malignant transformation into colon cancer occurs almost invariably approximately 10 years after the appearance of the polyps. FAP most commonly results from mutations in the ''APC'' gene, which normally functions to inhibit activity of the beta-catenin transcription factor. FAP is inherited in an autosomal dominant pattern. Thus, one copy of the altered gene is sufficient to cause the disorder.
FAP does not have a gender predominance and accounts for less than 1% of cases of colon cancer. Because mutation of the APC gene may occur spontaneously, patients may not be aware of the diagnosis until symptoms manifest. Most commonly, patients present during adolescence with constipation, diarrhea, abdominal pain, palpable abdominal masses, and weight loss. Prophylactic surgery is generally recommended before the age of 25 to prevent the development of colon cancer. There are several surgical options that involve the removal of either the colon or both the colon and rectum for patients with FAP. Extra-intestinal non-malignant tumors that may be associated with FAP include: fibromas, lipomas, sebaceous cysts, epidermoid cysts, osteomas, nasopharyngeal adenomas, and soft-tissue desmoid tumors. Extra-colonic cancers may also be associated with FAP, such as pancreatic mucinous adenocarcinomas, hepatoblastomas, and brain tumors. Gardner syndrome is a subtype of FAP that is characterized by the presence of colonic polyps, osteomas, soft tissue tumors, congenital hypertrophy of retinal pigment epithelium (CHRPE), and supernumerary teeth. Also, Turcot syndrome is characterized by FAP and the presence of malignant CNS tumors. |
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 |
Linked Question | Linked:: |
Order in Linked Questions | LinkedOrder:: |