WBR0544
| Author | [[PageAuthor::Rim Halaby, M.D. [1], Reviewed by Will Gibson, (Reviewed by Alison Leibowitz)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Neurology, SubCategory::Oncology |
| Prompt | [[Prompt::A 14-year-old male is brought to the physician's office by his mother for recent-onset headache, vomiting, and ataxia. Following appropriate work-up, the patient is found to have hemangioblastoma in the cerebellum and bilateral renal cell carcinomas. Genetic testing leads to a diagnosis. Which of the following findings is most likely associated with the patient's condition?]] |
| Answer A | AnswerA::Hematocrit (Hct) = 58 % |
| Answer A Explanation | AnswerAExp::Polycythemia is associated with renal cell carcinomas. Both sporadic renal cell carcinomas and Von-Hippel-Lindau associated renal cell carcinomas universally exhibit biallelic inactivation of the VHL tumor suppressor gene. |
| Answer B | AnswerB::Serum sodium = 122 mmol/L |
| Answer B Explanation | [[AnswerBExp::Hyponatremia is not frequently associated with VHL. Disorders of sodium can be associated with other cancers. For example, hyponatremia can be caused by an ADH-secreting small cell lung cancer. Conversely, Conn syndrome refers to an aldosterone-secreting adenoma, which typically causes hypernatremia.]] |
| Answer C | AnswerC::Serum alanine aminotransaminase (ALT) = 241 IU/L |
| Answer C Explanation | AnswerCExp::Elevated ALT is not frequently associated with VHL. Elevated ALT is associated with liver damage. |
| Answer D | AnswerD::Platelet count = 43,000 per microliter |
| Answer D Explanation | AnswerDExp::Thrombocytopenia is not frequently associated with VHL. Thrombocytopenia can occur in hematopoetic malignancy. |
| Answer E | AnswerE::Serum calcium = 13 mmol/L |
| Answer E Explanation | AnswerEExp::Hypercalcemia is not frequently associated with VHL. |
| Right Answer | RightAnswer::A |
| Explanation | [[Explanation::The patient has von Hippel-Lindau (VHL) disease, an autosomal dominant disorder caused by germline mutation of one copy of the VHL tumor suppressor gene on chromosome 3. VHL is characterized by hemangioblastomas of the retina, cerebellum, and medulla. Also patients frequently present with bilateral renal cell carcinomas or other tumors, such as pheochromocytomas. A common manifestation of VHL in young patients are headaches with neurological symptoms. Symptoms of other tumors may also manifest, such as hypertension in the case of pheochromocytoma. VHL encodes a ubiquitin ligase that targets the HIF (hypoxia inducible factor) protein for degradation. In the absence of VHL protein, renal cell carcinoma cells turn on a transcriptional program mimicking that of an oxygen-deprived state. The cells begin to highly express genes such as VEGF (vascular endothelial growth factor) that induce tumorigenesis. Recall that the kidneys are responsible for coordinating the erythropoetic response to low oxygen tension. Accordingly, renal cell carcinomas express high levels of erythropoietin and patients often develop high hematocrits. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Von hippel lindau, WBRKeyword::Polycythemia, WBRKeyword::Hematocrit, WBRKeyword::HCT, WBRKeyword::Hemangioblastoma, WBRKeyword::Bilateral renal cell carcinoma, WBRKeyword::Renal cell carcinoma, WBRKeyword::Headache, WBRKeyword::Vomiting, WBRKeyword::Pheochromocytoma, WBRKeyword::Hypoxia inducible factor, WBRKeyword::HIF, WBRKeyword::Autosomal, WBRKeyword::Autosomal dominant, WBRKeyword::Genetics, WBRKeyword::Inheritance, WBRKeyword::Cancer, WBRKeyword::Mutation, WBRKeyword::Cancer predisposition syndrome, WBRKeyword::VHL, WBRKeyword::Kidney cancer |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |