A 10-year-old girl is brought to clinic for laboratory follow-up. Her mother was recently diagnosed with von Hippel-Lindau (VHL) disease, and the patient received genetic testing. Examination is unremarkable. Laboratory evaluation reveals a missense mutation in the VHL gene. Periodic surveillance with which of the following is most likely to be of benefit in this patient?

Question

A 10-year-old girl is brought to clinic for laboratory follow-up.  Her mother was recently diagnosed with von Hippel-Lindau (VHL) disease, and the patient received genetic testing.  Examination is unremarkable.  Laboratory evaluation reveals a missense mutation in the VHL gene.  Periodic surveillance with which of the following is most likely to be of benefit in this patient?

Quizplus · Accepted Answer

11ec160b_39a7_9d64_9249_edd4af6bcbf8_MD0001_00 Von Hippel-Lindau (VHL) disease is an autosomal dominant condition caused by a loss-of-function mutation in the VHL gene on chromosome 3. The VHL gene product is a tumor suppressor protein that promotes degradation of damaged proteins and aids in cell cycle regulation. Similar to other disorders affecting tumor suppressor genes (eg, familial retinoblastoma), a second, somatic mutation in this gene leads to the development of various benign and malignant tumors (eg, cerebellar and retinal hemangioblastomas, pheochromocytomas, renal cell carcinomas) with potentially serious complications. Pheochromocytoma is a rare neoplasm arising from the adrenal medulla that can produce catecholamines (eg, epinephrine, norepinephrine). Patients may have hypertension, tachycardia, and sweating due to sympathetic overactivity; however, many are asymptomatic. As such, annual screening for increased urinary or plasma metanephrines (catecholamine breakdown products) is recommended. Likewise, screening for hemangioblastomas and renal cell carcinoma can be achieved with regular MRI and retinal examinations. (Choice A) The results of bone marrow evaluation would be abnormal in patients with leukemia, which is not associated with VHL disease. (Choice B) Chest radiography can identify lung metastases in a patient with a known malignancy. This patient requires evaluation for primary associated neoplasms before screening for metastases. (Choice C) Colonoscopy is performed in patients with an inherited predisposition to colorectal cancer, such as those with hereditary nonpolyposis colorectal cancer (ie, Lynch syndrome) and familial adenomatous polyposis. VHL disease is not associated with an increased risk of colorectal cancer in younger patients. (Choice D) Screening echocardiography is performed in patients with tuberous sclerosis complex to identify an associated cardiac rhabdomyoma. Cardiac tumors are not a significant feature of VHL disease. Educational objective: Von Hippel-Lindau (VHL) disease is an autosomal dominant condition caused by a mutation in a tumor suppressor gene, which is associated with the development of pheochromocytomas, retinal and cerebellar hemangioblastomas, and renal cell carcinomas. Because of the potential for serious complications from these tumors, patients with VHL should receive annual surveillance, including plasma metanephrines, abdominal imaging, ophthalmologic examination, and MRI of the brain and spine. __________ References: Pheochromocytoma screening initiation and frequency in von Hippel-Lindau syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/26451910) Von Hippel-Lindau disease. (http://www.ncbi.nlm.nih.gov/pubmed/27617152)

A 10-Year-Old Girl Is Brought to Clinic for Laboratory Follow-Up