The correct answer is E. The patient has bilateral acoustic neuromas, probably due to neurofibromatosis type 2, an autosomal dominant inherited disease. Over 90% of patients with NF-2 develop bilateral acoustic neuromas. This condition is associated with the NF2 gene, located on 22q (note all the 2's). Patients often develop neurofibromas, meningiomas, gliomas, and schwannomas of cranial and spinal nerves.
3p (choice A) contains the von Hippel-Lindau gene (von Hippel-Lindau (VHL) syndrome). The VHL protein is involved in regulation of a protein called hypoxia inducible factor 1 alpha (HIF1a). With VHL syndrome, the mutated VHL protein does not bind to HIF1a, which then activates transcription of genes for vascular endothelial growth factor and erythropoietin. Patients present with angiomatosis/ hemangioblastoma of the CNS, retina, and spine. There is also an association with pheochromocytoma and bilateral renal cell carcinoma.
5q (choice B) contains the APC tumor suppressor gene, which is associated with familial (Familial adenomatous polyposis syndrome) and sporadic colorectal cancers. Beta-catenin is controlled by the APC protein. Regulation of beta-catenin prevents stimulation of cell division and cell overgrowth. Thus APC gene mutations cause loss of control of cell proliferation, causing cells to proliferate. Familial adenomatous polyposis syndrome have numerous (thousands) of polyps in the colon.
13q (choice C) contains the Rb tumor suppressor gene, which is associated with retinoblastoma and osteosarcoma. Retinoblastoma tumors arise in the retina and patients present with loss of the red light reflex (leukocoria). The defective gene can be inherited from either parent. Inheritance is autosomal dominant. Heterozygotes can develop a mutation in the normal gene (2nd hit of the two-hit hypothesis). Retinoblastoma patients who survive retinoblastoma can also develop osteosarcoma later in life.
17q (choice D) contains the NF-1 tumor suppressor gene, which is associated with neurofibromatosis type I . Patients present with freckling of the skin (café au lait spots), neurofibromas, Lisch nodules, and increased risk for astrocytomas.
MedEssentials (4th Ed.): pp. 72, 73
First Aid (2018): pp. 60.1, 64.1
First Aid (2017): pp. 56.1, 60.1
First Aid (2016): pp. 71.1, 75.1
Pathoma (2018): pp. 192.3
Pathoma (2014-2017): pp. 190.3
Choice A: 7% chose this answer.
Choice B: 10% chose this answer.
Choice C: 9% chose this answer.
Choice D: 19% chose this answer.
Choice E: 55% correctly chose this answer.
Neurofibromatosis type 2 (NF2):
- Have bilateral acoustic neuromas.
- NF2 gene is located on chromosome 22.
- Additional clinical manifestation include neurofibromas, meningiomas, gliomas, and schwannomas of cranial and spinal nerves.
